research area center for molecular biosciences (cmbi) · bringing together these research units...

scientific report |2016/2017

Scientific Coordinators

Bert Hobmayer, Ronald Micura, Jörg Striessnig

Research Area Center for Molecular Biosciences (CMBI)

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Content: Bert Hobmayer, Professor of Zoology

Ronald Micura, Professor of Organic Chemistry

Jörg Striessnig, Professor of Pharmacology

Layout: Stephanie Brejla, Gabi Reiter

Contact: Research Area Center for

Molecular Biosciences (CMBI)

University of Innsbruck

Innrain 80-82a

A-6020 Innsbruck

Tel: +43 512 507-57501

Fax: +43 512 507-57599

[email protected]

www.uibk.ac.at/cmbi

© 2018 by CMBI

imprint |

Cover figure:

Induced neural stem cells (iNSCs) being reprogrammed from human skin fibroblasts by the team of

CMBI group leader Frank Edenhofer. Colonies of proliferating iNSCs start to differentiate into neurons

in the periphery. Differentiating neurons exhibit characteristic outgrowth of TUJ1-positive neurites

(green) that reach out to contact other neurons to build a functional network.

In our biannual report, the Center for Molecular Biosciences of Innsbruck University (CMBI) presents

its recent scientific achievements, new developments in ongoing research projects and success

stories of its faculty members, especially of young researchers. Molecular biosciences represent one

of the most exciting fields of modern research among the natural sciences. They bridge the gap

between single molecules and the complex functions in living organisms under normal conditions

and in disease. Minor changes in bioactive molecules such as DNA, RNA and proteins affect and

change the properties of cells, microorganisms, animals and plants. Advances in technologies

including microscopic imaging, new generation sequencing applications and techniques to

analyze molecular structures result in an explosion of information and understanding of biological

systems primarily oriented to improve human health. The CMBI aims at providing a platform for

this extremely rapidly developing research field by taking advantage of the visibility and expertise

of the CMBI’s internationally competitive groups to strengthen interdisciplinary research activities.

The CMBI currently consists of 21 research teams originating from the faculties of Chemistry and

Pharmacy, of Biology, and of Mathematics, Informatics and Physics, and their activities focus on

research and teaching. CMBI members contribute to the FWF special research program SFB-F44

“Cell Signaling in Chronic CNS Disorders”, which is currently in its second funding period, and

to several FWF-funded doctoral programs, all in collaboration with the Medical University of

Innsbruck. Notably, several member labs have now initiated a first CMBI-embedded university PhD

program under the topic “Ageing and Regeneration”. Furthermore, CMBI members were able

to successfully compete in the recent FFG call for university infrastructure and now establish new

facilities for Nuclear Magnetic Resonance (NMR) spectroscopy. These will significantly advance

biomolecular structural analysis in the Western-Austrian area. In order to cross-link with the

Tyrolean Life Science community and to foster career perspectives of young scientist, the CMBI is

a co-organizer of the internationally visible Innsbruck Life Science meetings, and it has started to

coordinate its activities as a core research unit within the newly established initiative “Tyrolean

Health and Life Science Cluster”.

In spite of these achievements, the CMBI faces challenges of general and also local nature. Rapid

technological progress in the Life Sciences requires ongoing investments into essential state-of

the art infrastructure. Ever-increasing demand for big data sets needs development of adequate

computing units and bioinformatics expertise. More than half of the 21 research teams are located

together with Life Science research departments of the Innsbruck Medical University in the recently

built Center for Chemistry and Biomedicine (CCB) building at the university’s central campus. Nine

of those, however, are spatially fragmented at the Technics Campus, the Department of Botany,

and the Research Department for Biomedical Aging Research. Bringing together these research

units within a single research campus would strongly stimulate scientific interactions and facilitate

the efficient use of expensive infrastructure. Long-term strategies towards this goal are needed to

enable competition with a large number of Life Science Research centers rapidly emerging across

Europe. All these issues require coordinated efforts at academic and political levels.

The CMBI coordinators:

Bert Hobmayer Jörg Striessnig Ronald Micura

The Research Area Center for Molecular Biosciences Innsbruck (CMBI) – a life science network in western Austria

Imprint

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Contents

Overview 6

CMBI - news

CMBI - specials 10

Research Summary

Signal transduction in cellular growth control and

carcinogenesis

18

Advanced chromatographic and spectroscopic analytical

tools in natural product analysis & molecular biology

20

Characterization of RNA, proteins, and their noncovalent

complexes by mass spectrometry

22

Gastropod metallothioneins in evolution: New rules for an

old protein family

24

Radiation damage in biological compounds induced by low

energy electrons

26

Regenerative potential of reprogrammed neural stem cells 28

Immuno-gerontology 30

Development of selectively acting antitumor drugs 32

Developmental biology and bioadhesion in basal animal

model systems

34

Molecular and cell biology of human aging 36

Plant biochemistry and metabolism 38

Chemistry, chemical and structural biology of the pigments

of life

40

Protein dynamics and biomolecular recognition 42

Developmental biology 44

Synthesis, structure, and function of non-coding RNAs 46

Cell physiology and gene regulation 48

Structure-functional activity relationship investigations on

ligands interacting with opioid receptors

50

Targeted proteolysis in human diseases and its impact on

drug development and production

52

Cell signaling in chronic CNS disorders 54

Pharmacognosy – combining traditional knowledge with

innovation

56

Biomolecular NMR spectroscopy 58

Publications 60

CMBI - careers of young researchers 92

Awards & Honors for CMBI scientists 96

CMBI Meetings and Seminar Series 99

The Research Area Center for Molecular Biosciences (CMBI) at the

University of Innsbruck is an integrative and multidisciplinary research

and teaching institution. The mission of the CMBI is to advance studies on

the structure, function, and interaction of biological macromolecules and

low molecular weight compounds relevant for cellular growth, metabolism,

and development. The research activities in the CMBI take advantage of

existing research strength in different fields and have strongly promoted

interdisciplinary research activities in five major fields of biomolecular sciences.

Twenty-one research groups from the faculty of Chemistry and Pharmacy,

the faculty of Biology, and the faculty of Mathematics, Informatics &

Physics are members of the CMBI.

Basic and applied biomolecular research fields at the CMBI

• Structure, dynamics and interactions of biologically important molecules

• Molecular basis of physiological and pathophysiological processes

• Metabolites, natural and synthetic compounds that modulate important

biological processes

• Cell-to-cell communication and cellular function

• Development, regeneration and aging of whole organisms

mem

ber

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Overview Overview6 7

CMBI members received scientific awards and prizes over the last two

years thus documenting their successful research activities also to the

scientific community and general public. Among those are the Bruker

research award 2017 and the Research Award of the Stiftung Südtiroler

Sparkasse 2017 to Hermann Stuppner, the Edmund Optics Educational

Award Europe 2017 to Torsten Schwerte, and the Würdigungspreis des

Bundesministeriums für Wissenschaft, Wirtschaft und Forschung 2017

to Anita Siller. Ilse Kranner was elected as President of the Austrian

Society of Plant Biology (ATSPB). Furthermore, several CMBI members

are members of the Austrian Academy of Sciences (Kathrin Breuker,

Ronald Micura, Bernhard Kräutler, Jörg Striessnig) and of the German

Academy of Sciences, Leopoldina (Bernhard Kräutler, Jörg Striessnig).

The activities of the CMBI are currently coordinated by Bert Hobmayer

(head), Jörg Striessnig and Ronald Micura.

In the years 2013 - 2017 the CMBI member labs published 737 papers

in peer reviewed journals. This includes 28 publications in the world

leading journals Nature, Nature Structural Biology, Nature Genetics,

Nature Cell Biology, Nature Chemical Biology, Nature Neuroscience,

Nature Communications, Nature Methods, Proceedings of the

National Academy of Sciences of the United States of America, and

Scientific Reports, 2 papers in Cell and 38 papers in top journals of

chemistry and physics, including Journal of the American Chemical

Society, Chemical Society Reviews, Angewandte Chemie and EMBO

J. The total amount of outside grant support of the last three years

amounts to about 9,4 Mio. €. Modern infrastructure obtained through

special governmental funding for research equipment significantly

strengthens research in structural and cell biology, bioanalytics and

biophysics at the CMBI.

CMBI members Areas of expertise

Chemistry

K. Bister, M. Hartl, E. Stefan biochemistry, molecular genetics

G. Bonn, C. Huck bioanalytics

K. Breuker biomolecular mass spectrometry

B. Kräutler, T. Müller structural biology, natural products chemistry

K. Liedl, D. Schuster theoretical chemistry, computer-aided molecular design

R. Micura chemical biology of nucleic acids

R. Schneider, B. Auer molecular biology, biotechnology

M. Tollinger, C. Kreutz biomolecular NMR spectroscopy

Pharmacy

R. Gust medicinal chemistry, drug design

H. Schmidhammer, M. Spetea pharmaceutical chemistry, drug design

J. Striessnig, A. Koschak, N. Singewald cell biology, neuropharmacology

H. Stuppner, M. Ganzera pharmaceutical biology, phytochemistry

Biology

R. Dallinger cell physiology, ecotoxicology

F. Edenhofer stem cell biology

B. Grubeck-Loebenstein immuno-gerontology

B. Hobmayer, P. Ladurner cell and developmental biology

P. Jansen-Dürr cell biology, molecular biology

I. Kranner plant physiology and biochemistry

D. Meyer, P. Aanstad developmental biology

B. Pelster, A. Sandbichler, T. Schwerte cell biology, cell physiology

Physics

S. Denifl biophysics, radiation physics

>> CMBI facts

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top

ics

| Research topics

• Protein and nucleic acid structure, folding, and dissociation in the gas phase (Breuker)

• Proteomics, metabolomics, phytomics (Bonn, Huck)

• Inelastic interaction of low energy electrons with molecules of biological relevance

(Denifl)

• Development of theoretical and computational methods describing molecular interac-

tions in chemical and biological systems (Liedl, Schuster)

• Biomolecular NMR spectroscopy (Tollinger, Kreutz)

• Synthesis, structure, and function of chemically modified RNA (Micura)

• Regulation of cell function by protein modification (Auer, Schneider)

• Oncogenic transcription factors and their cellular targets (Bister, Hartl, Stefan)

• Natural products chemistry, chemical and structural biology of the pigments of life

(Kräutler, Müller)

• Bioactive natural products from the plant kingdom (Stuppner, Ganzera)

• Development of potential drugs interacting with opioid receptors (Schmidhammer,

Spetea)

• Development of selectively acting antitumor drugs (Gust)

• Ion channels as new drug targets and the neuropathological basis of anxiety disorders

(Striessnig, Koschak, Singewald)

• Cell ion and volume homeostasis and metabolic activity (Pelster, Sandbichler, Schwerte)

• Trace element homeostasis in animal cells (Dallinger)

• Molecular and genetic control of vertebrate development (Meyer, Aanstad)

• Stem cell differentiation, regeneration and bioadhesion of basal Metazoa (Hobmayer,

Ladurner)

• Stem cell biology, cellular reprogramming & regeneration (Edenhofer)

• The aging T cell repertoire and its impact on vaccinations of the elderly (Grubeck-Loe-

benstein)

• Biology of aging, mitochondrial physiology (Jansen-Dürr)

• Stress metabolites and signalling pathways in plants (Kranner)

The specific research topics of the 21 CMBI member labs are listed below.

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With a new infrastructure worth two million Euros, interdisci-

plinary research on RNA at the University of Innsbruck will be

further strengthened. Since November 2017, two new NMR

spectrometers are available to scientists.

Models of high-energy excited states of nucleic acids

The structural dynamics of nucleic acids and their interactions with

proteins or small molecule compounds has already been successfully

researched at the University of Innsbruck in several working groups.

With the acquisition of new nuclear magnetic resonance (NMR)

spectrometers with frequencies of 400 and 700 MHz, this research

focus will be further strengthened. With their application to the 1st

F&E Infrastructure Call (2016) of the Austrian Research Promotion

Agency FFG, the Innsbruck scientists around Ronald Micura, Christoph

Kreutz, Martin Tollinger, Kathrin Breuker, Ronald Gust, and Hermann

Stuppner prevailed in a very tough Austria-wide competition. “The

new devices expand the possibilities in the area of structural chemistry

and they complement the existing spectrometers, which have been

fully utilized for several years”, says a delighted Ronald Micura.

The new infrastructure will further enhance the international visibility

of the various fields at the Center for Molecular Biosciences. Several

research groups are concerned here with the structure and folding

of RNA and their interaction with low molecular weight compounds.

Complex dynamic folding mechanisms are involved, which can be

elucidated by means of NMR spectroscopy. Another focus is on the

study of RNA-modifying enzymes and proteins that can trigger allergies

or are relevant to inflammatory signaling pathways, and in the search

for plant-derived natural products that can exert antibacterial effects

via RNA target molecules.

“The wealth of information that can be made accessible by NMR

spectroscopy is an ideal complement to the ‘static’ crystallographic

images of biomolecular systems, and it is poised to become the

method of choice for studying the dynamic interaction networks of

biomolecules for understanding in cells”, says Ronald Micura. Based

on the new infrastructure, the research groups of Robert Konrat from

the Max F. Perutz Laboratories in Vienna, Fatima Ferreira-Briza at

the University of Salzburg and Michael Oberhuber at the Laimburg

Research Center in South Tyrol, who are involved in comprehensive

scientific cooperation, will also benefit.

CMBI news CMBI news

>> NEW NMR-SPECTROMETERS

picture: Otto Peter

>> SEEING THE INVISIBLE – RNA AND DNA EXCITED STATES

Using nuclear magnetic resonance (NMR) spectroscopy, unexpected

high-energy excited states of nucleic acids could be detected and

characterized. These transiently existing conformations are present

at < 10%, but they represent important functional intermediates

in cellular processes. These states were addressed via novel NMR

spectroscopic methods. It could be shown, that a small, undesired

modification of DNA, a methylation, induces highly localized

transiently populated structural alteration in base pairing. These

high energy states very likely serve as a beacon for repair enzymes

and are therefore very important for the preservation of genetic

information. In contrast, naturally occurring RNA methylations lead

to drastic structural changes and expand the functional properties

of RNA. The different behavior of DNA and RNA could also explain

why nature stores the genetic information in the double helix of DNA

and not in the evolutionarily much older RNA. The work was done

by international cooperation with working groups at Duke University

(USA), Max F. Perutz Laboratories in Vienna and University College

London (UK).

Juen MA et al. Excited States of Nucleic Acids Probed by Proton Relaxation Dispersion NMR

Spectroscopy. Angew. Chem. Int. Ed. 55, 12008 (2016).

Zhou H et al. m1A and m1G disrupt A-RNA structure through the intrinsic instability of Hoogsteen

base pairs. Nature Structural & Molecular Biology 23, 803–810 (2016).

Structural model of ribozyme function

>> ELUCIDATION OF RIBOZYME STRUCTURES AND MECHANISMS

Three years ago, four new classes of ribozymes were discovered.

Like enzymes, these RNA species accelerate chemical reactions in the

cell. A research group led by Ronald Micura and researchers in China

around Aiming Ren have now elucidated the structure of the so-called

Twister-Sister ribozyme. The sequence design and the syntheses for

the investigations were done in Innsbruck, the crystallization and

X-ray structure analysis was undertaken by the scientists at Zhejiang

University in Hangzhou. Moreover, the Micura group also investigated

the Pistol ribozyme and elucidated its chemical mechanism. The

functional analysis was laborious, because the chemists had to

synthesize numerous new variants of this RNA, each of which only a

single atom was exchanged. Only then was it possible to check which

of the modified ribozymes is still functional. From this, it was possible

to deduce the positions responsible for reaction catalysis in the RNA

structure.

Zheng L et al. Structure-based insights into self-cleavage by a four-way junctional twister-sister

ribozyme. Nature Communications 8, 1180 (2017).

Neuner S et al. Atom-Specific Mutagenesis Reveals Structural and Catalytic Roles for an Active-Site

Adenosine and Hydrated Mg2+ in Pistol Ribozymes. Angew. Chem. Int. Ed. 56, 15954–15958 (2017).

CMBI - specials

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CMBI - specials

Klaus Bister from the Department of Biochemistry and Eric Hunter

from the Emory University (Atlanta) have served as editors for a special

volume - Viruses, Genes, and Cancer - of the book series Current Topics

in Microbiology and Immunology. The editors were able to engage

eminent researchers from the cancer field as contributors for this

volume, including the Nobel laureates Mike Bishop (San Francisco),

Harold Varmus (New York), and Harald zur Hausen (Heidelberg). The

chapters focus on virus-host cell interactions, cellular genes acquired

or modulated by viruses, the pathological effects of these interactions,

and therapeutic interventions. Several articles specifically address the

role of viruses and genes – such as oncogenes, proto-oncogenes, or

tumor suppressor genes – in the etiology of human cancer. Oncogenic

signaling by PI3 kinase, mTOR, Akt, or the major cancer drivers MYC

and RAF, and the role of tumor suppressors like p53, are discussed

in detail. The volume also explores the emerging role of noncoding

RNAs such as microRNAs in tumorigenesis and cancer therapeutics.

Hunter E, Bister K (eds). Viruses, Genes, and Cancer - Current Topics in Microbiology and

Immunology, Vol. 407. Springer International Publishing (2017).

Stefan E, Bister K. MYC and RAF: Key effectors in cellular signaling and major drivers in human

cancer. Curr. Top. Microbiol. Immunol. 407, 117-151 (2017).

>> MOLECULAR BASIS OF CANCER AND OTHER CHRONIC DISEASES

>> „INNSBRUCK” MODEL ORGANISM: TRANSGENESIS ESTABLISHED

The free-living flatworm Macrostomum lignano is a suitable model

system for regeneration, reproduction, evolution and bio-adhesion

research. However, a major cornerstone of research methods – the

ability to generate transgenic animals – was missing for Macrostomum

and the whole flatworm community. In cooperation with colleagues

from the European Institute for the Biology of Ageing (Groningen,

NL), the Ladurner group published the generation of stable

transgenic Macrostomum lines expressing fluorescent proteins under

several tissue-specific promoters. The reported method will permit

sophisticated research approaches including gene overexpression,

dissection of gene regulatory elements, real-time imaging and lineage

tracing. It provides a technological platform for harvesting the power

of Macrostomum as an experimental model organism for flatworm

biology and biomedical research.

Wudarski J et al. Efficient transgenesis and annotated genome sequence of the regenerative

flatworm model Macrostomum lignano. Nature Communications 8, 2120 (2017).

CMBI news CMBI news

Various transgenic Macrostomum lines expressing

fluorescent proteins under tissue-specific promoters

An international research team including the group of Frank Edenhofer

investigated the role of gap junctional intercellular communication

(GJIC) by generating Connexin43/Connexin45-double deficient mouse

embryonic stem cells. These Connexin double-knock-out cells show

almost complete breakdown of GJIC and a block of differentiation

in embryoid bodies. However, pluripotency marker expression and

proliferation are unaffected. They fail to form primitive endoderm

in embryoid body cultures, representing the inductive key step of

gastrulation-like events. At a molecular level, GJIC-incompetent

embryonic stem cells exhibit significantly less activated NFATc3 in

cellular nuclei than control cells suggesting that Connexin-mediated

communication is needed for synchronized NFAT activation to induce

orchestrated primitive endoderm formation.

Wörsdörfer P et al. Abrogation of gap junctional communication in ES cells results in a disruption of

primitive endoderm formation in embryoid bodies. Stem Cells 35, 859-871 (2017)

>> GAP JUNCTIONAL INTERCELLULAR COMMUNICATION ESSENTIAL

FOR ENDODERM FORMATION

Development of embryonic stem cells of the inner cell mass

into endodermal and ectodermal tissue layers

Researchers of the German Cancer Research Center and the team of

Frank Edenhofer at the Institute of Molecular Biology have identified

that Myc depletion in mouse embryonic stem cells results in a

reversible biosynthetic dormancy and proliferation arrest. Likewise,

Myc inhibition in mouse blastocysts induces dormancy mimicking

hormonally controlled diapause without affecting the pluripotency

capacity, suggesting the importance of Myc regulation in controlling

entry and exit from stem cell dormancy during development.

Furthermore, Myc-depleted stem cells and diapause embryos do

exhibit similar expression signatures. Thus, dormancy is a transient

stem cell state, molecularly defined by low levels of Myc expression,

where the most primitive cells within the stem cell compartment can

be stored as a transiently quiescent reservoir to preserve genomic

integrity and be protected from microenvironmental hazards and

replicative stress.

Scognamiglio R et al. Myc depletion induces a pluripotent dormant state mimicking diapause. Cell

164, 668–680 (2016).

Working model for Myc-induced dormancy in stem cells

>>NEW ROLE FOR MYC IN STEM CELL DORMANCY AND SELF RENEWAL

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CMBI - specials

CMBI news CMBI news

Using a combination of pharmacophore models for soluble epoxide

hydrolase and 5-lipoxygenase activating protein, Daniela Schuster

and her co-workers discovered and participated in a detailed

characterization of a potent dual inhibitor targeting both proteins

in sub-micromolar concentrations. The substance, which was

named Diflapolin, selectively inhibited leukotriene formation and

epoxyeicosatrienoic acid degradation, and was not active against

other targets from the arachidonic acid cascade. Importantly, it

showed anti-inflammatory activity in vivo in mice. A patent was filed

on this and structurally related compounds, and they are currently

optimized towards more favorable properties in collaboration with

Prof. Matuszczak and Mag. Vieider.

Temml V et al. Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and

soluble epoxide hydrolase using pharmacophore-based virtual screening. Scientific Reports 7,

42751 (2017).

Garscha U et al. Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor

of 5-lipoxygenase-activating protein and soluble epoxide hydrolase. Scientific Reports 7, 79398

(2017).

>> DISCOVERY OF DIFLAPOLIN AS AN ANTI-INFLAMMATORY SUBSTANCE

>>MICRO-RNA MIR-144 AND ANXIETY DISORDER

Effective long-term treatment for fear, trauma and anxiety-related

disorders is a continuing challenge. One emerging new treatment

strategy is combining exposure-based cognitive behavioural therapy

with extinction-facilitating drugs. We, in collaboration with national

and international partners identified a specific microRNA, mir-144,

that is critically involved in orchestrating the rescue of impaired

extinction learning. Its expression was shown to be decreased in

extinction-impaired mice and upregulated upon extinction learning

in extinction-competent mice. We identified an important locus of

action, since overexpression of mir-144 in the amygdala was sufficient

to fully rescue the extinction learning impairment. Since specific

drugs have been shown previously to increase mir-144 expression,

this route will be followed to develop drug-based strategies to boost

and normalize aberrant fear-inhibitory learning, which is a common

deficiency observed in human anxiety disorders.

Murphy CP et al. MicroRNA-mediated rescue of fear extinction memory by miR-144-3p in extinction-

impaired mice. Biol. Psychiatry 81, 979-989 (2016).

Nicolas Singewald and his team

Daniela Schuster (left) and Veronika Temml (right)

Recent research of Bernhard Kräutler and his group brought major

further discoveries concerning the biological role of the seasonal

disappearance of chlorophyll, as well as on the metabolic function

and molecular logic of vitamin B12.

The abundant and highly visual green leaf pigment chlorophyll is

broken down in plants by strictly regulated biological processes

furnishing ‘phyllobilins’ in an amount of 1000 million tons each

year on Earth. In contrast to all earlier views, phyllobilins are now

presumed to have physiological functions that are still enigmatic,

but possibly similar to those of related heme catabolites, such as

the yellow bilirubin. Attractive roles of phyllobilins in plants could

concern photo-regulation, as well as pathogen defense. We have

studied yellow phyllobilins recently and discovered their behavior as

medium responsive photo-switches, a property that hints at a possible

role in photo-regulation.

In order to understand better some of the proposed enigmatic

(‘moonlighting’) activities of the B12-cofactors, we have recently

suggested to study effects of ‘antivitamins B12’, structural analogs

of vitamin B12 that cannot function as the vitamin does. Thus, these

types of ‘wolf in a sheep’s clothes’ inhibit the canonical enzymatic

B12-functions, enabling researchers to determine the intact structures

of key enzymes. In this context, a synthetic methodology to the

particularly intriguing group of analogs of vitamins B12 has been

recently opened up, in which the B12’s own cobalt center is replaced

by another transition metal, such as the homologue rhodium. This

extremely difficult chemical task was achieved in collaboration

with biologists in England, providing the long awaited road to

fundamentally new B12-analogues and a new group of excellent

enzyme inhibitors.

Ruetz et al. Antivitamin B12 inhibition of the human B12 -processing enzyme CblC: Crystal structure

of an inactive ternary complex with glutathione as the cosubstrate. Angew. Chem Intl. Ed. 56, 7387

(2017).

Li et al. Chlorophyll-derived yellow phyllobilins of higher plants as medium-responsive chiral

photoswitches. Angew. Chem Intl. Ed. 55, 15760 (2016).

Widner et al. Total synthesis, structure, and biological activity of adenosylrhodibalamin, the non-

natural rhodium homologue of coenzyme B12. Angew. Chem Intl. Ed. 55, 11281 (2016).

>> CHLOROPHYLL AND VITAMIN B12 - TWO ‘PIGMENTS OF LIFE’

Phyllobilin structure and autumn leaves with disappearing

chlorophyll

16 17

CMBI - specials

CMBI news CMBI news

The CavX project has been established as a doctoral program with

a cell- and neurobiological focus on cellular signaling through ion

channels. The research groups of Alexandra Koschak, Petronel Tuluc

and Jörg Striessnig are the CMBI project leaders in the newly FWF-

funded doc.funds project CavX together with colleagues from the

Medical University (Marta Campiglio, Bernhard E. Flucher and Gerald

Obermair, who also serves as a CavX coordinator). This program

provides a special platform for the training of graduate students in

cellular signaling in electrically excitable cells. The FWF doc.funds

initiative was started only recently and has been awarded for the

first time in fall 2017. 45 proposals were submitted and from those

an international multidisciplinary jury selected 16 for a final hearing.

Seven of those were finally recommended for funding. The application

process of the CavX program was strongly supported and guided by

the vice-rectors for research of the two participating universities.

In a transnational approach combining research competences in

structural chemistry, medicine and molecular biology, the molecular

details of apple allergy are studied and potential apple varieties for

therapy of birch pollen allergy are identified. Roughly 20% of the mid-

European population are affected by birch pollen allergy, and more

than 70% of them subsequently develop allergic reactions to apples

due to cross-reactivity of IgE antibodies between homologous proteins

in birch pollen and apples. This immunological cross-reaction may

present an opportunity to use apples in a controlled and established

dosage to cure birch pollen allergy. Using NMR spectroscopy, the

three-dimensional structures of different isoforms of the major apple

allergen, the protein Mal d 1, and the birch pollen allergen Bet v 1 are

compared in order to identify those apple varieties ideal for successful

long-term therapy of birch pollen allergy by apple consumption.

Within the framework of the project “applecare”, complementary

research competences in Tyrol and South Tyrol are pooled, including

the Laimburg Research Centre, Bolzano Hospital, Innsbruck Medical

University and the University of Innsbruck.

>> FWF-FUNDED DOCTORAL DOCFUNDS PROGRAM „CAVX“ STARTS AT THE

INNSBRUCK UNIVERSITIES WITH CMBI PARTICIPATION

>> START OF THE INTERREG V-A ITALIA-ÖSTERREICH PROJECT „APPLECARE“

FUNDED BY THE EUROPEAN REGIONAL DEVELOPMENT FUND

Researchers from the Institute of Molecular Biology cooperated with

Stefan Kubicek, Group Leader at the CeMM (Vienna), to demonstrate

in vivo the beta cell-promoting effects of artemisinins, compounds

which were discovered through screening efforts in cell lines to steer

alpha cells towards a beta cell fate. In work done by the group of

Dirk Meyer, zebrafish with severely reduced beta cells were treated

with artemisinins. This resulted in increased beta cell numbers

and normalized glucose levels. Chemicals which enhance beta cell

production have potential as therapies for diabetes, in which these

critical cells are lost. Follow up studies have been aimed to more

precisely define the effects of artemisinins.

Li J et al. Artemisinins target GABAa receptor signaling and impair α cell identity. Cell 168, 86-100

(2017).

>> ARTEMISININS AS POTENTIAL COMPOUNDS IN DIABETES THERAPY?

>> NEWLY IDENTIFIED STRESS PROTEIN PROTECTS SNAILS

Snails are model organisms for research on metal stress and

detoxification of heavy metals. As other animals, they use

Metallothionein proteins to bind and neutralize heavy metals such

as cadmium. An international research team organized by Reinhard

Dallinger including collaborators in Zurich and Barcelona succeeded in

isolating and characterizing an unexpected form of Metallothionein

protein from a marine snail, which exhibits three instead of two metal-

binding motifs. Thereby, one of these proteins is able to bind nine

Cadmium ions, much more than other Metallothioneins, resulting in

a much higher detoxification efficiency and higher stress resistance of

theses snails. Identification of this new protein structure is a result of

a FWF DACH project on the evolution of the Metallothionein protein

family funded together with the Swiss National Science Foundation

SNSF.

Baumann C et al. Structural adaptation of a protein to increased metal stress: NMR structure of

a marine snail Metallothionein with an additional domain. Angew. Chem. Int. Ed. 56, 4617-4622

(2017).

Commented on by: Fahrenkamp-Uppenbrink L. Heavy metals? No problem for this snail. Science

356, 150-151 (2017).

The “applecare” team at the CMBI: R. Eidelpes, L. Ahammer,

J. Unterhauser and M. Tollinger (left to right)

18 19

>> Goal: Molecular mechanisms of cellular growth control and

carcinogenesis

>> Background: Research in our lab is focused on the analysis of signal

transduction pathways, mediated by plasma membrane receptors,

second messengers, cytoplasmic kinases, and transcriptional regulators.

Both physiological and pathogenic forms of these pathways are

investigated, with specific focus on their role in carcinogenesis.

>> Research Highlights and Outlook: The bHLH-LZ (basic region/

helix-loop-helix/leucine zipper) oncoprotein Myc and the bHLH-LZ

protein Max form a binary transcription factor complex controlling

fundamental cellular processes. Deregulated Myc expression leads to

neoplastic transformation and is a hallmark of most human cancers. Myc

transcription factor activities are controlled by defined protein-protein

interactions (PPI). We have recently obtained evidence for a second

messenger controlled physical interaction between the Ca2+ sensor

calmodulin (CaM) and all Myc variants (v-Myc, c-Myc, N-Myc, and L-Myc).

The predominantly cytoplasmic Myc:CaM interaction is Ca2+-dependent,

and the binding site maps to the conserved bHLH domain of Myc.

Ca2+-loaded CaM binds the monomeric and intrinsically disordered Myc

protein with high affinity, whereas Myc:Max heterodimers show less,

and Max homodimers no affinity for CaM. NMR spectroscopic analyses

corroborate the biochemical results on the Myc:CaM interaction and

confirm the interaction site mapping. Cell-based reporter analyses and

cell transformation assays suggest that increasing CaM levels enhance

Myc transcriptional and oncogenic activities. Our results point to a

possible involvement of Ca2+ sensing CaM in the fine-tuning of Myc

function.

Myc is regulated by several signaling cascades implicated in

development and oncogenesis. The Wnt/β-catenin/Tcf axis drives

cell differentiation and organismal patterning. Disturbances of this

pathway - like mutation of the APC tumor suppressor in colon cancer

- leads to tumorigenic processes including transcriptional deregulation

of the c-myc protooncogene. The early diploblastic cnidarian Hydra has

two myc genes (myc1, myc2), with myc2 being closer related to c-myc.

Wnt/β-catenin signaling has crucial functions in cell differentiation and

development in Hydra. In collaboration with the Hobmayer group,

we found that activation of Wnt/β-catenin signaling in Hydra leads

to downregulation of myc1 but not of myc2. Mapping and analysis

of the myc1 and myc2 promoter regions revealed the presence of

consensus binding sites for the transcription factor Tcf. In vivo binding

of Hydra Tcf to both promoter regions was demonstrated by chromatin

immunoprecipitation. Reporter gene assays showed that the myc1

promoter is repressed by ectopic Hydra β-catenin/Tcf, whereas the myc2

promoter was not affected. The identification of the Wnt/β-catenin/

Tcf axis as a regulatory pathway of Hydra myc genes indicates that

principal links in the Wnt signaling network have emerged very early in

metazoan evolution.

At the plasma membrane an array of more than 800 G protein-coupled

receptors (GPCRs) receive, convert, amplify, and transmit incoming

signals. Activated GPCRs team-up with intracellular scaffolding proteins

to compartmentalize signal transmission. Scaffolds, such as β-arrestin

and A-kinase anchoring proteins (AKAPs), function as a physical nexus

between receptors and molecular switches. Typically, these receptor-

bound AKAPs recruit protein kinase A (PKA) to assemble dedicated

polyvalent signaling complexes that are spatially and temporally

confined. We showed that the orphan GPCR, Gpr161, is a PKA substrate

and also has an AKAP motif embedded in its C-terminal tail. Our results

suggest that Gpr161, by directly recruiting type I PKA holoenzymes

to the receptor, creates a cAMP-sensing signalosome. Furthermore,

we propose that Gpr161 plays a role in recruiting isoform-specific

PKA complexes to primary cilia. Currently we analyze and perturb the

receptor-effector relationship in the primary cilium.

>> Research GrantsFWF: P23652 (2011-2016), P27606 (2015-2018), P30441

(2017-2021), SFB-F44 associated member (2015-2016),

TWF: UNI-0404/1525 (2014-2016); TWF: UNI-0404/1990

(2017), Alfonso M. Escudero fellowship (2015-2016)

>> CoworkersV. Bachmann, P. Raffeiner, O. Torres-Quesada (postdocs);

M. Bucher, F. Enzler, A. Feichtner, J. Mayrhofer, R. Röck,

C. Schneider, B. Texler (master and Ph.D. students); S.

Beiler, K. Puglisi, A. Raffeiner, A. Reintjes (technicians)

Signal transduction in cellular growth control and carcinogenesis

Klaus Bister, Markus Hartl, and Eduard Stefan

>> Department of Biochemistry

Figure 1: Schematic diagram of basic interconnections

between Myc and Ca2+/CaM signaling. The binding reactions

and equilibria involved are indicated by black dashed arrows,

cytoplasmic proteolytic processing or nuclear transport of

Myc is depicted by red or green arrows, respectively. Specific

cleavage to Myc-nick requires the action of Ca2+-dependent

proteases (red dashed arrow). (Raffeiner et al., Oncotarget

2017)

Figure 2: Schematic depiction of the canonical Wnt signalling

pathway. Wnt binds to the Frizzled (FZD) receptor leading

to disruption of the APC/GSK3β complex which normally

degrades β-catenin (β-Cat). Accumulated β-Cat translocates

into the nucleus where it binds to the Tcf transcription factor

leading to transcriptional activation of Wnt signalling targets

via Tcf binding elements (TBE, 5’-CCTTTGA/TA/T-3’). (Gufler et

al., Dev. Biol. 2018, Epub 2017; Hartl et al., unpublished).

Figure 3: PPI network emanating from PKA. Following phos-

phoproteomic analyses using LC-MS/MS, a static PPI network

of the confident set of PKA interacting proteins (endogenous

complexes isolated from osteosarcoma cells) was generated.

(Bachmann*, Mayrhofer* et al., PNAS 2016).

Research summary Research summary

20 21 Research summary

Christian Huck and Günther Bonn

>> Department of Analytical Chemistry and Radiochemistry

>> Goal: Novel chromatographic and vibrational spectroscopic tools with

enhanced efficiency, selectivity and sensitivity, are developed in order to

get detailed analytical information upon the composition, origin and/or

species of samples in the fields of phytomics, metabolomics, proteomics

and foodomics.

>> Background: The development of novel monolithic stationary phases

for the separation of small molecules was highly successfully continued.

Those stationary phases have been designed for either sample

preparation by solid phase extraction (SPE) or analytical separations by

high performance liquid chromatography (HPLC). Thereby, the monolithic

format offers several advantages, including superior efficiency, high

permeability, mechanical robustness, and extended useful life-circle.

New methodologies for solid-phase extraction (SPE) based on polymeric,

highly selective and hydrophilic mixed-mode have been established.

The incorporation of an, e.g., imidazole residue featured auspicious

characteristics including possible analyte interactions via hydrophobic as

well as hydrogen bonding or pH dependent electrostatic interactions.

By the additional post-polymerization derivatization, imidazole was

converted into a strong ion-exchanger which increasingly extended the

application of solid-phase extraction in analytical platforms.

In the field of vibrational spectroscopy the development of non-invasive,

fast techniques based on near-&mid-infrared (NIR&MIR), Raman

spectroscopy plays a crucial role enabling simultaneous analysis of physical

and chemical parameters, respectively. The development of miniaturized

portable spectrometers is highly useful. Imaging and mapping MIR/NIR/

Raman methods are developed for screening of sample composition with

a spatial resolution down to 1 µm, which enables the development of

early diagnosis tools for cancer detection. Quantum chemical calculation

for spectrum simulation can provide substantial support especially in the

interpretation of complex spectra. In case of low concentrated analytes

the combination of selective enrichment techniques with IR and/or

Raman spectroscopy has been shown to be suitable. These techniques

are termed as SEIRS (Surface enhanced infrared spectroscopy); MEIRS

(Material enhanced infrared spectroscopy) and SERS (Surface enhanced

Raman spectroscopy).

>> Research Highlights and Outlook: The realization of polymeric

monolithic sorbents with retention mechanisms based on more than

one type of interaction was realized and this type is referred to as mixed

mode stationary phases. Fast gradient separations allowed the analysis

of alkyl benzenes and parabens within a few minutes. Compared to

silica based particles, the polymeric stationary phase provides pH

stability over the complete pH range and its preparation as monolith

in capillary successfully shows several advantages compared to packed

columns.

Polymeric mixed-mode stationary phases are of high importance

regarding their use as small SPE columns in sample preparation

approaches. For that polymeric mixed-mode sorbents were based on

an imidazole network and feature auspicious characteristics including

a high polarity, an aromatic system and good points of applications for

further derivatizations. It comprised suitable applications for complex

samples containing lipophilic aromatic or aliphatic frameworks as well

as opposing polar, acidic substance classes (Figure 1).

One aim of Huck´s lab is the development of non-invasive NIR portable

measurement technology for the determination of optimum harvest

time for medicinal plants (phytomics). With this approach it is for the

first time possible to detect within one measurement quality related

chemical parameters such as the concentration of distinct ingredients

and also physical parameters, e.g. anti-oxidative and or anti-bacterial

activity, respectively. Thereby, reference analytical methods as described

in the prior paragraph play a crucial role next to quantum chemical

spectrum simulation and 2D-COS (Figure 2).

Since the milk and horsemeat scandal it became clear that early food

fraud detection is essential. Therefore, it is the aim to develop easy

applicable vibrational spectroscopic tools in order to determine the

origin and/or species of food such as apples, milk, cheese, meat and

cereals. Additionally, NIR/MIR and especially Raman Imaging is highly

suitable for the discrimination of cancerous tissue from healthy with

a resolution down to 1 µm. These techniques give promise that in due

time non-invasive light fiber based measurement can be applied.

>> Research GrantsFFG GZ 859502; OEAD GZ ZA 07/2017; EPU 53/2016,

EPU 54/2016; Interreg GZ AB116; Interreg GZ ITAT1005;

BMWFW 402.000/003-II/6b/2012

>> CoworkersPD Dr. Rania Bakry, Assoz.-Prof. Dr. Matthias Rainer,

Prof.Dr. Sevgi Türker (visiting professor); Mag.Dr.

Cornelia Pezzei, Dr. Justina Grabska, Dr. Krzysztof Bec,

(postdoc); Mag. Lukas Bittner, Mag. Raphael Henn,

Mag. Markus Huber, Stefanie Delueg MSc, Mag. Karl

Handle, Mag. Christian Kirchler, Verena Wiedemair

MSc., Anel Beganovic MSc., Sophia Mayr MSc. (Ph.D.

students); Andreas Agerer, Sebastian Lörcher (diploma

students)

Advanced chromatographic and spectroscopic analytical tools in natural product analysis & molecular biology

Figure 2: Strategy for the development of an on-line quality

assurance procedure of medicinal plants

Figure 1: HPLC chromatograms of a mustard seeds extract

before and after SPE using Poly(NVI/EGDMA). Highly acidic,

water soluble glucosinolates are interacting with the

quaternized imidazolium ring by ion-exchange interactions.

Displacement during elution process is enabled by counter-

ions of high relative binding strengths.

Research summary

22 23 Research summary Research summary

activated dissociation (CAD), thus allowing its use for probing tat

binding sites in TAR RNA by top-down MS. At the same time, the MS

data revealed time-dependent 1:2 and 1:1 stoichiometries of TAR-tat

complexes and suggest structural rearrangements of TAR RNA induced

by tat peptide binding.

Many RNA-protein and RNA-drug complexes involve interactions

between guanidine and phosphate moieties. We have investigated

noncovalently bound complexes of an 8 nt RNA and six different

ligands, all of which comprise a guanidinium moiety, by electrospray

ionization (ESI) and CAD MS, and found that the order of complex

stability correlated almost linearly with the number of ligand atoms

that can potentially be involved in hydrogen bond or salt bridge

interactions with the RNA but not with the proton affinity (PA) of

the ligands. However, ligand dissociation in CAD of the complex ions

was generally accompanied by proton transfer (PT) from protonated

ligand to deprotonated RNA, indicating conversion of salt bridge into

hydrogen bond interactions. The relative stabilities and dissociation

pathways of the (RNA+mL-nH)n- complexes of differing stoichiometry

(m = 1-5) and net charge (n = 2-5) revealed both specific and unspecific

ligand binding to the RNA.

Nucleobase methylations are ubiquitous posttranscriptional

modifications (PTMs) that can substantially increase the structural

diversity of RNA in a highly dynamic fashion with implications for

gene expression and human disease. Especially for noncoding RNAs,

research progresses at a high rate but is still critically hindered by

lack of adequate methodology for the characterization of PTMs; high

throughput deep sequencing does not generally provide information

on PTMs. We have investigated how specific nucleobase methylations

affect RNA ionization in ESI, and backbone cleavage in CAD and electron

detachment dissociation (EDD), and developed two new top-down MS

approaches for the characterization of RNA methylations in mixtures

of either RNA isomers or nonisomeric RNA forms. Fragment ions were

analyzed to identify the modification type, to localize the modification

sites, and to reveal the site-specific, relative extent of modification for

each site.

>> Research Grants

FWF Y372, FWF P27347, FWF P30087

>> CoworkersHeidelinde Glasner, Eva-Maria Schneeberger, Jovana

Vusurovic, Matthias Halper, Giovanni Calderisi, Simon

Chwatal

Figure 3: Top-down MS using CAD can identify RNA

modifications, localize modification sites, and reveal the

site-specific, relative extent of modification for each site in

mixtures of RNA isomers or forms (H. Glasner, C. Riml, R.

Micura, K. Breuker Nucleic Acids Res. 45, 8014-8025, 2017)Figure 1: Native top-down MS reveals the sites of tat peptide

binding to TAR RNA in the 1:2 complex (E.M. Schneeberger,

K. Breuker Angew. Chem. Int. Ed. 56, 1254-1258, 2017).

Figure 2: CAD MS of RNA-guanidine derivative complexes

shows that their stability increases with the number of ligand

atoms that can be involved in hydrogen bond or salt bridge

interactions, but not with the proton affinity of the ligands

(J. Vusurovic, E.M. Schneeberger, K. Breuker ChemistryOpen

6, 739-750, 2017).

>> Goal: A major focus of our research is to explore the determinants

of biomolecular structure, stability, binding, and dissociation in the gas

phase. Based on insight from fundamental and mechanistic studies,

we develop new methodology for protein and ribonucleic acid (RNA)

characterization by mass spectrometry (MS), including the identification,

localization, and relative quantitation of posttranslational and

posttranscriptional modifications, and the determination of

stoichiometry and binding sites of noncovalent complexes of RNA.

>> Background: Mass spectrometry is an evolving technique with unique

potential for biomolecular characterization beyond mere sequencing.

Current research in the field aims, for example, at developing “top-

down” and “middle-down” MS approaches for studying different

proteoforms, posttranscriptional modifications of non-coding RNA, and

the higher order structure of functional biomolecular assemblies, for

which a solid understanding of biomolecular gas phase ion structure,

stability, binding, and dissociation is critical.

>> Research Highlights and Outlook: RNA frequently associates with

proteins in many biological processes. The characterization of RNA-

protein complex structures and binding interfaces by NMR spectroscopy,

X-ray crystallography, or strategies based on chemical crosslinking,

however, can be quite challenging. We have explored the use of an

alternative method, native top-down mass spectrometry, for probing of

complex stoichiometry and protein binding sites at the single-residue

level of RNA. Our data showed that the electrostatic interactions

between HIV-1 TAR RNA and a peptide comprising the arginine-rich

binding region of tat protein are sufficiently strong in the gas phase

to survive phosphodiester backbone cleavage of RNA by collisionally

Kathrin Breuker

>> Department of Organic Chemistry

Characterization of RNA, proteins, and their noncovalent complexes by mass spectrometry


Reinhard Dallinger

>> Department of Zoology

>> Goal: To achieve an extensive perception of the potential and

significance of metallothionein (MT) genes and proteins for metal

metabolism in animals by exploring their evolution and diversification

towards novel structures and functions in different animal lineages.

>> Background: For a long time, MT research has been focused on the role

and significance of this protein family in vertebrates (mainly mammals)

and a few selected model organisms. We believe, however, that the

true potential of a protein family can only be comprehended and

acknowledged by encompassing its structural and functional diversity

across all major organismic phyla. During the last years, a plethora of

primary MT sequences has been provided from a variety of different

bacteria, plants, fungi and animal lineages. Our group has contributed

to a better understanding of structural and functional MT diversity by

in-depth research of MT structures and functions in the mollusk clade

of Gastropoda (limpets, snails and slugs). These animals represent, in

terms of evolutionary radiation, one of the most successful and diverse

animal phyla whose members have successfully adapted, several times

independently, to life in terrestrial and freshwater habitats. One of the

most challenging questions in this concern is, to which extent gastropod

MT structures and functions have been inherited from marine ancestors,

and by how much they may have undergone adaptive modifications

upon transition from sea to land and to freshwater environments.

>> Research Highlights and Outlook: Through evolution of gastropod

MTs, there has been a trend towards diversification into metal-specific

isoforms, with a particular prevalence, in some gastropod lineages (such

as Stylommatophora snails), of Cd- and Cu-selective MTs (Palacios et al.

2011). Evidently, Cd specificity has evolved prior to Cu specificity and must

therefore, be regarded as the ancestral metal-specific feature, occurring

today in species of both, Caenogastropoda and Heterobranchia snails

(Figure 1). In some Cd-selective MTs, the capacity of metal loading has

been boosted by addition of one Cd binding protein domain, as shown

by us for the first NMR structure of a three-domain MT from the marine

snail Littorina littorea in cooperation with the Oliver Zerbe group

(University of Zürich) (Baumann et al. 2017). More recently, we discovered

a further three-domain Cd MT structure in Pomatias elegans, a close

terrestrial relative of Littorian littorea (Schmielau et al., submitted). In

some other species of Caenogastropoda and Heterobranchia snails, the

Cd loading capacity has been boosted by invention of MT isoforms with

as much as 10 (ten!) Cd-binding domains, as recently discovered by us in

Alinda biplicata (Heterobranchia) (unpublished data, Figure 1). In most

cases, Cd specificity at the protein level is accompanied by Cd-specific

upregulation of respective CdMT genes. Interestingly, Cu-selective MT

isoforms have evolved from pre-existing Cd-specific ancestral variants

only in species of the Stylommatophora lineage (terrestrial snails in

the clade of Heterobranchia) through gene duplication, followed by

structural modification towards Cu selectivity. This has been achieved,

among others, by increasing in the primary structure of CuMTs the

K : N (lysine : asparagine) ratio, which indicates that the selectivity

towards distinct metal ions may at least in part be owing to structural

constraints affecting the ionic charge and size of metal binding pockets

in the MT metal clusters (Palacios et al. 2011). A striking difference to

other animal MTs is the evident lack of Zn2+ affinity in gastropod MTs.

Instead, in Gastropoda this metal ion is consistently associated with low-

molecular metal binding ligands such as phytochelatins or carbohydrate

compounds (unpublished data, in preparation). As an intriguing

outlook, it becomes more and more apparent that one additional

and so far neglected functional significance of MTs in gastropods, and

perhaps in other animal clades too, may be their important protective

role in favor of Ca2+ pathways (unpublished data, in preparation).

References

Palacios et al. 2011, BMC Biology BMC 2011, 9:4, 1-20.

Baumann et al. 2017, Angew. Chem. Int. Ed. 56, 4617-4622.

Schmielau et al. 2018, Sci. Tot. Environ., submitted.

>> Research GrantsFWF I1482-N28 (DACH, leading agency: FWF); FWF

I3032-B21 (DACH, leading agency: FWF)

>> CoworkersVeronika Pedrini-Martha (postdoc); Reinhard Lackner

(technical assistance); Michael Niederwanger, Martin

Dvorak, Raimund Schnegg (Ph.D. students); Lara Schmi-

elau (diploma student)

Gastropod metallothioneins in evolution: New rules for an old protein family

Figure 1: Flowchart of MT evolution in Gastropoda, showing

the major gastropod subclasses (Patellogastropoda,

Vetigastropoda, Neritimorpha, Caenogastropoda and

Heterobranchia) on the left-hand site. Two-domain MTs of

low or no metal specificity at all have so far been observed

in Patellogastropoda, Vetigastropoda and Neritimorpha

(above, in blue). In contrast, metal-specific MT isoforms

(CdMTs and CuMTs) have evolved in Caenogastropoda and

Heterobranchia (middle and lower part). Two-domain Cd-

specific isoforms (as found in Pomatias elegans) are ancestral

and have given rise to higher-molecular MT structures by

addition of a third (like in Littorina littorea) or even up to

ten (as in Alinda biplicata) Cd-binding domains (middle part,

in red). Cu-specific MT isoforms have been derived in some

Heterobranchia by gene duplication from two-domain Cd-

specific ancestors (lower part, in green). In some families of

Heterobranchia, metal specificity has finally been lost again

by primary structure modification.


Stephan Denifl

remains bound to an intact THF molecule due to the high proton affinity

of the molecule. Rather unexpected is the exclusive formation of (THF

– OH)+ from clusters, since in this case intramolecular bond cleavage

is favored over intermolecular bond cleavage although substantial

energy is deposited by the colliding electron. However, additional

experiments with the deuterated molecule allowed an unambiguous

identification of this reaction channel, since we observed the loss of

OD in this case. Studies with the deuterated compound also allowed

the identification of reaction pathways in the case of nanohydration.

In case of nanohydrated THF, fragmentation of the sugar is reduced in

favor of fragmentation by the solvent molecules.

Finally, we recently also intensified our studies with potential

radiosensitizers developed for the improvement of radiation therapy.

For future studies on the molecular level, nitroimidazolic compounds

will be promising since those compounds have been successfully

established for radiation therapy in Nordic countries.

>> Research GrantsFWF-I1015, FWF-P22443

>> CoworkersMichael Neustetter (postdoc), Jusuf Khreis, Anita Ribar,

Rebecca Meißner, Joao Ameixa (Ph.D. students), Katha-

rina Fink, Bea Haslwanter, Julia Reitshammer (master

students)

Radiation damage in biological compounds induced by low energy electrons

Figure 1: Electron ionization mass spectrum of isolated

tetrahydrofuran (orange line) and tetrahydrofuran clusters

(black line), respectively. Both spectra were recorded at the

electron energy of about 70 eV. In case of clusters, a peak is

present at m/z 55, which can be assigned to the loss of OH

from tetrahydrofuran.

>> Goal: Exploring negative and positive ion formation by secondary

electrons formed upon radiation of biological compounds.

>> Background: A large number of secondary particles are generated

when energetic primary radiation (e.g. photons, ions or cosmic

radiation) interacts with biological material like living cells. The most

abundant secondary species formed are electrons which are released

with an average kinetic energy of a few eV. These electrons subsequently

interact with cell components before they become a chemically inactive

species. The electron interaction may however be severe even leading

to single and double strand breaks of DNA. Therefore it is crucial

to investigate the interaction of low energy electrons with simple

biomolecules representing building blocks of biological material

(nucleobases, amino acids, etc.). Mass spectrometry of anions formed

by electron attachment represents our experimental approach.

>> Research Highlights and Outlook: In recent experiments we carried out

mass spectrometric studies with clusters of tetrahydrofuran. Studies in

the field of chemical physics often use tetrahydrofuran (THF) as model

compound for the sugar moiety of DNA. The clusters were created by

the so-called supersonic expansion technique and crossed with a beam

of electrons. Figure 1 shows the resulting mass spectrum below the

monomer, when THF clusters are ionized by electrons with the kinetic

energy of about 70 eV. Most of the ions formed correspond to those

when a single THF molecule is ionized. Only two exceptions can be

found: The protonated THF ion and the (THF – OH)+ ion are not found

in the mass spectrum for the single molecule. The former ion is easily

formed by fragmentation of a larger cluster, where the weak bond

between the THF moieties is broken upon the ionization, and a proton

>> Department of Ion Physics and Applied Physics

28 29

>> Goal: To obtain human neural stem cells for disease modeling and

cell therapy

>> Background: The Edenhofer group is working with mammalian

stem cells and has a long-standing interest in cellular regeneration

and disease modeling particularly of neurological disorders. Cellular

reprogramming enables the derivation of induced pluripotent stem

cells (iPSCs) from somatic cells such as skin or blood cells. iPSCs are

functionally equivalent to embryonic stem cells (ESCs) i.e. they exhibit

an unlimited differentiation and self renewal potential. We aim at i)

understanding the transcriptional program of stemness properties, ii)

exploring novel 2nd generation reprogramming paradigms and iii)

harnessing the potential of patient-specific reprogrammed cells for

biomedical applications such as disease modeling and cell therapy.

>> Research Highlights and Outlook: One aim of our lab is the elucidation

of transcriptional regulation of self-renewal of mammalian stem cells.

Self-renewal belongs with differentiation to the major features of

stem cells that are closely associated with cell cycle progression. The

molecular processes underlying the choice between cell division,

differentiation and dormancy are uniquely regulated in stem cells and

represent a fundamental principle to control cell type specification,

organ homeostasis, and potentially tumorigenesis. We explored the

mechanistic role of transcriptional regulators Nanog and Myc in cell

cycle control of pluripotent stem cells. Nanog is a homeodomain

transcription factor that is necessary for the natural induction of

pluripotency in early mammalian development but dispensable for

its maintenance in vitro. We found that Nanog enhances cell cycle

progression of NIH 3T3, primary fibroblasts and ESCs by downregulation

of the cell cycle inhibitor p27KIP1 (also known as CDKN1B) establishing

a direct link between pluripotency establishment and cell cycle control.

The Myc family of transcription factors has been implicated in both

i) the induction of artificial pluripotency in somatic cells, and ii) the

generation of a variety of human tumors. In a collaborative study

with the group of Andreas Trumpp (German Cancer Research Center,

Heidelberg) we functionally analyzed the role of Myc in pluripotent

stem cells. Deletion of both c-myc and N-myc strongly decreases

transcription, splicing, and protein synthesis, leading to a proliferation

arrest. This study shows that Myc controls the biosynthetic machinery of

stem cells without affecting their potency, thus regulating their entry

and exit from the dormant state.

Cell fate specification of stem cells exiting the pluripotent state and

undergoing cell differentiation represents another key question that

our group addressed. In this respect we employed a 3D organoid model,

embryoid bodies (EBs), to study the role of gap junctional intercellular

communication (GJIC) in early embryonic development.

Connexin (Cx) 43 and Cx45 are co-expressed in ESCs, form gap junctions

and are considered to exhibit adhesive function and/or to contribute

to the establishment of defined communication compartments. We

generated Cx43/45-double deficient mouse ESCs and achieved almost

complete breakdown of GJIC. Cx43/45-dKO results in a block of

differentiation in EBs without affecting pluripotency and proliferation.

We further demonstrated that GJIC-incompetent ESCs fail to form

primitive endoderm in EB cultures, representing the inductive key

step of subsequent differentiation events. This work helps to gain

comprehensive understanding into mechanisms underlying early

lineage specification, which is essential in order to understand

embryonic development and stem cell based organoid cultures.

>> Research GrantsFWF I 3029-B30, FWF W 1206-B18, bmwfw 10.420-WF/

V/3c/2016, DFG AOBJ 635622

>> CoworkersKatharina Günther, Katharina Kruszewski, Jerome

Mertens, Sandra Rizzi, Ahmad Salti (postdoc); Anita

Erharter, Gabriella Fenkart, Larissa Traxler (Ph.D.

students); Veronika Fricke, Regina Gassler, Anna

Hausruckinger, Felix Strasser (master students); Marta

Suarez Cubero, Urban Tscheikner-Gratl (technicians);

Caroline Baldemair, Marion Staudinger (secretary)

Regenerative potential of reprogrammed neural stem cells

Frank Edenhofer

>> Department of Molecular Biology, Department of Genomics, Stem Cell Biology &

Regenerative Medicine

Figure 1: Genetic ablation of Cx43/45 by Cre/loxP-mediated

mutagenesis disrupts primitive endoderm formation in

embryoid bodies (EBs). (A-F): Immunofluorescence analyses of

the primitive endoderm marker Gata6 and the pluripotency

marker Nanog in EBs on day 6 of differentiation. Gata6 is

detectable in a substantial number of nuclei of 4-day-old

Cx43/45 flox EBs (A-C) while it is only rarely found in Cx43/45-

deficient cells (D-F). (G-H): Control EBs on day 6 exhibit a

well-structured surface layer of extraembryonic endoderm

(Gata6) (G) and a-feto protein (AFP). Cells of the outer Gata6-

and AFP-positive layer stained negative for the pluripotency

marker Nanog. A defined outer layer of Gata6-positive cells

was not observed in Cx43/45-deficient EBs (I). Scale: (A-F): 100

mm. Scale: (G-I): 50 mm.

Research summary Research summary


Beatrix Grubeck-Loebenstein

>> Research Department for Biomedical Aging Research

>> Goal: To gain a better understanding of age-related changes within

the immune system in order to find new ways to prevent the loss of

immune function with age.

>> Background: Age-related changes in T-lymphocytes, immune cells

responsible for eliminating virus-infected cells and cancer cells from the

body, are most detrimental. This is due to early degenerative changes

that take place in the thymus, the organ in which T cells mature. As the

thymus gradually loses its ability to replenish, the naïve T cells decrease

while memory and effector T cells increase in number and dominate

the repertoire. This can lead to the loss of certain T cell specificities and

changes in the composition of the T cell repertoire. One point of interest

in this respect is to explore the role of the bone marrow (BM) for the

maintenance of immunological memory in old age. Of practical relevance

is the question how vaccination can be optimized for the elderly.

>> Research Highlights and Outlook:

The bone marrow (BM) and immunological memory in old age:

The BM is important for the long-term maintenance of immunological

memory, but the influence of aging on the production of survival

factors for effector/memory T cells and plasma cells in the human

BM has not yet been investigated. We could demonstrate that the

expression of molecules involved in the maintenance of immunological

memory in the human BM changes with age. While IL-15 that protects

potentially harmful CD8+CD28− T cells increases, IL-7 decreases. IL-6 is

also overexpressed. In contrast, APRIL, a plasma cell survival factor for B

cells, is reduced. In contrast, IFN-y, TNF, and ROS accumulate in the BM

in old age. IL-15 and IL-6 correlate with ROS levels in BM mononuclear

cells. IL-15 and IL-6 are also overexpressed in the BM of superoxide

dismutase 1 knockout mice compared to their WT counterparts. Our

results demonstrate the role of inflammation and oxidative stress in age-

related changes of immune cell survival factors in the BM. Antioxidants

may therefore be beneficial in counteracting immunosenescence by

improving immunological memory in old age (Pangrazzi et al, Eur J

Immunol 2017;47:481-492).

Vaccination for the elderly:

Vaccines against tetanus and diphtheria are among the most frequently

used vaccines worldwide, but previous studies from our laboratory

have shown that protection against tetanus and particularly against

diphtheria is unsatisfactory in adults and older persons. In the course

of the EU project “MARK-AGE” we analyzed tetanus- and diphtheria-

specific antibody concentrations in 2100 adults of different age from 6

selected European countries (Austria, Belgium, Germany, Greece, Italy,

Poland) in order to investigate differences in the level of protection

against tetanus and diphtheria across Europe. The data demonstrate

that tetanus- and diphtheria-specific antibody concentrations vary

greatly between countries, which is also reflected in the percentage

of persons with antibody concentrations below the protective level

(0.1IU/ml), which ranged from 2 to 31% for tetanus and 28-63%

for diphtheria. In most countries, tetanus- and diphtheria-specific

antibody concentrations decrease with age. Tetanus-specific antibody

concentrations are generally higher in males than in females, whereas

no gender-related differences were found for diphtheria-specific

antibodies. The studies demonstrate that the European population is

not satisfactorily protected against tetanus and diphtheria. Protection

should be improved by a life-long perspective on vaccination and more

education to increase awareness of the necessity of regular vaccination

throughout life all over Europe (Weinberger B et al, Exp Gerontol 2017;

Oct 7. pii: S0531-5565(17)30516-8).

>> Research GrantsEU HEALTH-F4-2011-280873, EU SSH-2012-1-320333,

EU H2020-PHC-2014-2015-633964, EUREGIO-EFH, FWF

ZFW012530, ÖAW-DOC 24089, TWF UNI-0404/2018, D.

Swarovski 2015/BIO-15, D. Swarovski 2016/BIO-22

>> CoworkersCarmen Giefing-Kröll, Stella Lukas Yani, Andreas Me-

ryk, Birgit Weinberger (postdocs); Marco Grasse, Carina

Miggitsch, Erin Naismith, Luca Pangrazzi (Ph.D. stu-

dents); Daniel Breitenberger, Christina Putzer, Rebecca

Ralser (diploma students); Magdalena Hagen, Florian

Hatzmann, Franz Melzer (master students); Brigitte

Jenewein, Michael Keller (technicians)

Immuno-gerontology


Ronald Gust

>> Department of Pharmacy, Pharmaceutical Chemistry

>> Goal: Development of new antitumor drugs, which address new

targets to overcome intrinsic and acquired resistance of tumor cells.

>> Background: Nowadays cancer chemotherapy is yet accompanied

by limiting unwanted side effects and the development of intrinsic or

acquired resistance. Therefore, the search for new targets and novel

antitumor drugs are topics in the research of medicinal chemists.

Especially, metal-based drugs as alternatives to cisplatin and carboplatin

are of high interest. They should address not the DNA but other targets

in the tumor cells to circumvent cross-resistance. Of further interest

is the design of selective estrogen receptor modulators (SERM) with

a unique binding mode at the estrogen receptor to get alternatives

to tamoxifen with a safer hormonal profile. Therefore, we focussed

our interest on metal complexes, which i) inhibit the cyclooxygenase 2

(COX-2) over-expressed in mammary and colon carcinoma or ii) induce

ferroptosis, an iron-dependent form of non-apoptotic cell death. Our

new SERMs represent bivalent drugs with affinity to the ligand binding

domain (LBD) and the coactivator-binding site to exclude agonistic

growth stimulating effects.

>> Research Highlights and Outlook: In a preliminary structure activity

study we could show that the acetyl salicylic acid derivative [prop-2-

ynyl-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS) represents

an unselective COX-1/2 inhibitor with cytotoxicity against breast

cancer cells comparable to cisplatin. Exchange of the cobalt cluster

by [ethylene]trichloroplatinate(II) (Zeise´s salt) strongly increased the

inhibitory effects at COX-1, but drastically reduced the COX-2 inhibition

and the cytotoxicity. With the objective of increasing the selectivity for

COX-2, we introduced a chlorine substituent in position 3, 4, 5, or 6 at

the ASS moiety of Co-ASS. This substituent utilizes on the one hand

the larger binding cave of COX-2 to prevent activity at this isoenzyme

and on the other hand it reduces the binding to COX-1 due to steric

repulsion. Indeed, all complexes retained their activity at COX-2 and

were inactive at COX-1. In this context, we characterized the MDA-MB

231 breast cancer as well as the HT-29 colon carcinoma cells as COX-1/2-

positive and the MCF-7 breast cancer cells as COX-negative. The missing

COX content led to almost inactivity of the complexes against MCF-7

cells indicating that COX-2 is involved in the mode of action of the

Co-ASS derivatives.

Ironsalene complexes were designed to get a carrier-mediated uptake

in tumor cells. Inside the cells, they generate an iron-dependent

form of non-apoptotic cell death. This effect called ferroptosis is

morphologically, biochemically, and genetically distinct from apoptosis

and necrosis. It is induced by Fe(II/III) because of building of reactive

oxygen species and can be suppressed by the potent ferroptose-

inhibitor ferrostatin-1. With our compounds, it was demonstrated for

the first time that iron complexes can induce ferroptosis and free iron

ions are not a prerequisite.

Nuclear receptors play a crucial role in the development of hormone-

dependent tumors. Tamoxifen and fulvestrant are promising drugs in

the hormone therapy of the ER-positive mammary carcinoma. They

prevent in different ways the binding of coregulators to the activated

estrogen receptors thereby causing antiestrogenic properties. Our

approach targets both the ligand binding domain (LBD) and the

coactivator-binding site. 4-Hydroxytamoxifen (4-OHT) or derivatives

were linked by an alkyl spacer with small molecules, so called nuclear

receptor alternate-site modulators (NRAMs), which competes with the

coaktivator for its binding site (Figure 1). In this case, the LBD binder

(e.g. 4-OHT) causes selectivity for the ER and the coactivator can

effectively be prevented from ER activation. Dependent on the used

LBD binder, the dimers show high affinity to the ER only slightly lower

than estradiol. High advantages are the fluorescence properties, which

allow first investigations on the mode of action. The bivalent drugs are

vesicular accumulated in MCF-7 cells and were identified especially in

vesicles in the cytoplasm (Figure 2).

>> Research Grants

FFG (West-Austrian BioNMR)

>> CoworkersBenjamin Ma, Daniel Bäcker, Natalie Fahrner, Sina

Götzfried, Alexandra Knox, Robert Mauersberger,

Victoria Obermoser, Anna Schöpf, Alexander Weninger

(PhD students); Monika Cziferszky (postdoc)

Development of selectively acting antitumor drugs

Figure 1: Connection of the 4-hydroxytamoxifen derivative

GW 7604 with an alkylpyrimidine NRAM .

Figure 2: Intracellular localization in the cytoplasm of MCF-7 cells.


Bert Hobmayer and Peter Ladurner


>> Goal: We focus on stem cell differentiation during embryonic

development, tissue turnover and regeneration, and analyze bio-

adhesion in basal animal model organisms.

>> Background: By using simple model organisms such as cnidarian

polyps, flatworms, and sea squirts, we study basic molecular and cellular

processes of cell differentiation, pattern formation, and bioadhesion.

Of central interest are evolutionary conserved developmental pathways

and master regulatory genes known to act throughout the animal

kingdom. Thereby, we aim at a better understanding of molecular

mechanisms and transfer our knowledge to higher organisms in order

to point to potential targets for biomedical research. Furthermore,

we have started to characterize bio-adhesive substances used by our

animals to attach to the substrate.

>> Research Highlights and Outlook: We have characterized adhesive

proteins of the flatworm Macrostomum lignano using a transcriptomic

and high throughput in situ screen approach combined with Mass

spectrometry, confocal- and electron microscopy, RNA interference,

specific antibodies and Lectin staining. Flatworms have evolved

adhesives adapted to different environments such as freshwater,

seawater and parasite attachment onto its host. We have started to

identify bio-adhesives also in the cnidarian polyp Hydra and the larvae

of sea squirts. In addition, we now expand our search for bio-adhesives

to 20 different flatworm species. It is the goal to understand the

mode of action of these molecules to enable the development of new

synthetic counterparts.

The cnidarian polyp Hydra and various flatworm species show an

unparalleled capacity for whole body regeneration. In order to understand

cellular aspects of regeneration, the formation of organized tissue layers

was analysed including changes in apical-basal and planar polarities of

epithelial cells at the closing wound. These behaviours are under molecular

control of conserved signalling pathways. We have concentrated on

the role of the Wnt/beta-Catenin signalling pathway. It is activated by

initial wound healing and then orchestrates a regeneration-specific gene

regulatory network involved in position-specific differentiation events.

Regeneration is commonly based on the action of naïve, stem cell-like

cells, and their behaviour is regulated by stemness-factors of the Myc

family. The Hydra genome encodes for four myc gene family members

similar to the genomes of vertebrates and mammals. In a long-going

effort and in strong collaboration with the CMBI group of Bister/Hartl/

Stefan, we study these ancestral forms of Myc factors, their structural

and biochemical properties in comparison to mammalian Myc factors,

and their different roles in decision making in the interstitial stem cell

lineage of Hydra. First data sets suggest actions in stem cell self-renewal,

cell multiplication, but also nerve cell differentiation.

>> Research GrantsFWF 25404; FWF 30347; J4071 Schrödinger-Program;

Marie Curie FP7 626525; 4x ÖAW DOC Fellowships;

EU-COST Action Networks TD0906, CA15216, CA16203

>> CoworkersUte Rothbächer (Associate Professor); Bernhard Egger

(Assistant Professor); Marcelo Rodrigues (postdoc);

Birgit Lengerer, Robert Pjeta, Julia Wunderer, Willi

Kari, Sabine Gufler, Fan Zheng (PhD students); Lena

Zitzelsberger, Belinda Artes, Veronika Prantl, Willi Sal-

venmoser, Thomas Ostermann, Hermine Hohensinner

(technical assistants).

Developmental biology and bioadhesion in basal animal model systems

Figure 1: Transgenic flatworms expressing fluorescent

proteins in different cell lineages.

Figure 2: Live image of polarity changes in the actin

cytoskeleton of Hydra epithelial cells in a bud just evaginating

towards the right.


Pidder Jansen-Dürr

>> Research Department for Biomedical Aging Research

>> Goal: The group studies molecular mechanisms of cellular senescence

in human dermal fibroblasts and vascular endothelial cells, with a focus

is on the role of reactive oxygen species,. In addition, we are interested

in the role of mitochondrial proteins as regulators of senescence

and in age-associated metabolic dysregulation. We also investigate

the relationship between cellular senescence and age-associated

dysfunctions and diseases, such as skin aging and cardiovascular

diseases. Specific topics include the role of various stress signals on

cellular aging and age-associated pathologies of human tissues. We

also developed a new diagnostic test system for detection of HPV E7

proteins in cervical smears which was shown to be an efficient tool for

triage of HPV-positive women.

>> Background: The group has elucidated the role of oxidative stress

on senescence phenotypes of human endothelial cells and dermal

fibroblasts. To study molecular mechanisms underlying photoaging of

the skin, we have used a model for UVB induced cellular senescence of

human skin fibroblasts in which we identified protein quality control

mechanisms, such as proteasome activity and autophagy as new players

in cellular senescence of human dermal fibroblasts. We also developed

a quasi-physiological model for photoaging of the skin, consisting

of reconstructed human skin equivalents and used it to confirm the

role of protein quality control systems in skin aging. In addition,

the mitochondrial protein FAHD1 was identified as a new player in

regulation of mitochondrial function and cellular senescence; studies

of molecular mechanisms are underway.

>> Research Highlights and Outlook: Human Aging is modulated by a

complex network of interacting genetic pathways, which have been

elucidated through studies on lower eukaryotic model organisms,

such as yeast, flies and worms. However, not all mechanisms of aging

identified in animal models can be faithfully and completely translated

into human aging. Accordingly, there is a need to study aging processes

also in systems more closely mimicking human aging. In this respect,

the concept of cellular senescence has gained a lot of impact in the last

decade primarily by the discoveries that i) cellular senescence occurs in

aged organisms from primitive vertebrates up to humans and ii) the

recent demonstration that the accumulation of senescent cells in mouse

models drives the aging process.

In the Jansen-Dürr group, basic research and translational work is being

conducted on mechanisms of cellular senescence using model systems

reflecting aging of the human skin To this end we study human cells

which are grown in vitro to either achieve replicative senescence through

extended passaging (telomere shortening) or by using exogenous

stressors to drive cells in stress-induced premature senescence (SIPS). We

have extended previous findings aiming at a better understanding of

molecular mechanisms underlying UVB-induced senescence of diploid

human dermal fibroblasts (HDFs), an experimental model to study the

process of photoaging of the skin. Our data suggest that autophagy

is required for the establishment of the senescent phenotype in UVB-

treated HDFs and that inhibition of autophagy is sufficient to change

the cell fate from senescence to cell death by apoptosis (Fig. 1).

Studies in reconstructed skin equivalents revealed that UVB irradiation

triggers hallmarks of autophagy induction in the dermal layer. These

findings have potential implications for fundamental as well as

translational research into skin aging, in particular photoaging. (Fig. 2).

In a second project we have continued to characterize the function

of FAHD1, a newly discovered metabolic enzyme which is the first

eukaryotic member of the family of oxaloacetate decarboxylases. The

position of FAHD1 at the crossroads between carbohydrate metabolism

and fatty acid metabolism suggests that FAHD1 plays an important role

as metabolic key regulator. Phenotypic alterations of FAHD1 KO mice

relative to wild-type mice are currently being investigated. In an attempt

to speed up this analysis we also knocked down FAHD1 in human

umbilical vein endothelial cells (HUVEC). We found that depletion of

FAHD1 from human endothelial cells inhibited mitochondrial energy

metabolism and subsequently induced premature senescence. Whereas

senescence induced by FAHD1 depletion was not associated with

DNA damage, we noted a reduction of mitochondrial ATP-coupled

respiration associated with upregulation of the cdk inhibitor p21 (Fig. 3).

These results provide additional support to the growing evidence that

mitochondrial dysfunction can induce cellular senescence by metabolic

alterations independent of the DNA damage response pathway.

In collaboration with Mikrogen GmbH in Neuried, Germany, and a

clinical partner from Theassaloniki, Greece, we evaluated high-risk(hr)

HPVE7-protein detection as a triage method to colposcopy for hrHPV-

positive women, using a newly developed sandwich-ELISA-assay. This

assay could be a useful partner to HPV testing for cervical cancer

screening.

>> Research GrantsH2020 Marie Curie Actions RISE 691158 MediHealth,

EU FP7 305483 FRAILOMICS, Tiroler Wissenschaftsfond

UNI-0404/1625 ExomiR in OsteoAge, FFG Bridge 1

848474 Alpine Pflanzen in der Kosmetik, Swarowski

grants, industry grant Mikrogen GmbH, Neuried, Ger-

many, industry grant Cura Marketing GmbH, Innsbruck,

Austria, AWS Grant FAHD1 Inhibitors, COST Action

MITOEAGLE, PhD position LFUI Nachwuchsförderung

>> CoworkersHuaije Bu, Solmaz Etemad, Rafal Koziel, Maria Amalia

Cavinato Nascimento, Alexander Weiss (postdocs); Eva

Albertini, Giorgia Baraldo, Michele Petit, Christina

Metzger, Sophia Wedel (Ph.D. students); Max Holz-

knecht, Anne Buchmann (diploma students); Annabella

Pittl, Beata Szalka (technicians)

Molecular and cell biology of human aging

Figure 2: UVB-induced changes in the morphology of recon-

structed skin. Skin equivalents were submitted to UVB and

stained by hematoxylin–eosin for morphological analysis.

Figure 3: Depletion of oxaloacetate decarboxylase FAHD1

inhibits cell proliferation (A), induces cellular senescence in

human endothelial cells (B-C), and inhibits mitochondrial

function (D-E). SA-ß-gal activity was increased in FAHD1 KD

cells (B). Western blots showing the expression of FAHD1,

p53, p21, and γ-H2AX (C). Mitochondrial membrane poten-

tial (MMP) (D) and oxygen consumption rate (OCR) (E) were

reduced in FAHD1 KD cells.

Figure 1: UVB induces autophagy. (A) LC3-GFP expressing

HDFs were submitted to UVB and processed for confocal

microscopy. Wild type HDFs were subjected to the same

treatment and analyzed by (B) Western blot or (C) electron

microscopy. (A) Representative images of three indepen-

dent experiments showing the punctuation of LC3 upon

1, 2, 3, and 4 days of UVB treatment (D1, D2, D3 and D4,

respectively) and 3 days after the last UVB stress (D7). (B)

Representative Western blot showing the lipidation of LC3

upon UVB, where LC3-I corresponds to unlipidated and LC3-

II to lipidated form of the protein. (C) Electron micrograph

of cells submitted for 2 days to UVB irradiation and their

respective controls.


Ilse Kranner

>> Goal: To deepen our understanding of plant metabolism with the

aim to identify key molecular switchboards that determine plant stress

response.

>> Background: Plants are the basis of life on Earth. All food is directly

or indirectly derived from plants, and plants also produce the oxygen

we breathe. In other words: no plants, no food, no oxygen. The current

climate change is accompanied by stress factors such as drought

and elevated temperature - with potentially deleterious effects on

agriculture and biodiversity, compromising food security for an ever-

increasing human population. Our research group is dedicated to

making significant contributions to unravelling the molecular basis of

plant stress response. In the past two years, much of our work focussed

on research into the impacts of climate change on seed production of

crop plants. In addition, we worked on wild plant species from extreme

environments and of micro-algae, to further increase our understanding

of plant response to environmental stress factors. We use mainly

hyphenated techniques (UHPLC-MS/MS, GC-MS/MS) in combination

with spectrophotometric methods to identify check points in plant

metabolism that trigger cell, tissue and plant fate – to die or to survive.

>> Research Highlights and Outlook: In this reporting period, much

effort was directed towards delivering the € 3 million FP7 project

“Impacts of Environmental Conditions on Seed Quality” (EcoSeed).

Coordinated by the University of Innsbruck, the consortium involved

11 partners from five European countries. The EcoSeed project was

dedicated to unravelling the effects on seed quality of the stresses

predicted to occur more frequently due to climate change: elevated

temperature and drought. Using a full omics approach complemented

by various biochemical and biophysical techniques, four main species

were investigated, the model plant Arabidopsis thaliana, and the

crops Brassica oleracea, Helianthus annuus and Hordeum vulgare. A

complementing study of bread wheat showed that seed germination

is intricately regulated by thiol-disulphide conversions involving the

tripeptide antioxidant glutathione (γ-glutamyl-cysteinyl-glycine) in a

tissue specific manner.

>> Research Grants

EU FP7 grant 311840, EU FP7 Marie Curie grant 328370

>> CoworkersThomas Roach; Wolfgang Stöggl (Assistant Professors);

Erwann Arc, Beatriz Fernández-Marín, Chae Sun Na, Fa-

bio Candotto Carniel (postdocs); Davide Gerna, Gregor

Pichler (PhD students); Julian Wimmer, Theresa Baur

(MSc students); Birgit Stenzel, Bettina Lehr, Siegfried

Aigner (technicians)

Plant biochemistry and metabolism

Figure 1: Schematic representation of the involvement of hydrogen peroxide (H2O2) and low-molecular-

weight (LMW) thiols and disulphides during bread wheat germination and early seedling growth.

From left to right, changes in LMW thiol- disulphides and H2O2 production rates in Triticum aestivum:

in a whole dry seed, seed structures isolated from non-germinated seeds after 15h from the onset of

seed water uptake, and seed structures isolated from germinated seeds after 15 and 48h. Whole dry

seed, endosperm including aleurone (large oval), and embryo or seedling (small oval) are divided by

vertical lines. These lines delimit areas proportional to the concentrations of total glutathione [i.e.

GSH (glutathione) + GSSG (glutathione disulphide)], area left of line) and cyst(e)ine [i.e. Cys (cysteine)

+ CySS, (cysteine) area right of line], in the respective seed structure. The redox states (Ehcs in mV) of

total glutathione and cyst(e)ine are indicated by the blue-to-red (reducing-to-oxidising) shadings of

each area, as shown by the bottom right scale. Yellow background shadings indicate the rates of H2O2

production (nmol g-1 DW s-1), as shown by the bottom left scale. The dashed vertical line separates

seeds from seedlings. Taken from Gerna et al. Free Radical Research 51:6, 568-581.

>> Department of Botany


Chemistry, chemical and structural biology of the pigments of life

Bernhard Kräutler and Thomas Müller


Research summary

crystal structure was the first of a metal analogue of a natural B12-

derivative. The ‘mother’ ligand of vitamin B12, hydrogenobyric acid,

gave first insights into the intriguing capacity of the ‘contracted’ corrin

macrocycle for binding and activating transition metals. AdoRhbl and

other ‘antivitamins B12’ are inhibitors of B12-dependent enzymes and

interfere with B12-riboswitches, as predicted.

Our lab has also pioneered studies on the structure and chemistry of

chlorophyll catabolites from higher plants, named ‘phyllobilins’. In the

context of such studies we have become interested in the colored natural

‘phyllochromobilins’, which are strikingly similar, structurally, to bilins

derived from heme catabolism. Finding evidence for (still hypothetical)

physiological effects of phyllobilins in plants, animals and humans is

one of the goals of this research. Furthermore, we have developed

MALDI-TOF and DESI mass spectrometry imaging methodology for the

2D localization and identification of biologically relevant molecules in

biological tissue. The imaging studies on chlorophyll breakdown also

involved students from local partner high schools (’Sparkling Science’

project). Exciting results as well as simple experiments in this context

were presented to a broader public at the “Lange Nacht der Forschung

2016”.

>> Research GrantsFWF P-28522, FWF P-28892, Sparkling Science project

SPA/04-140/INDIAN SUMMER IN TYROL.

>> CoworkersCh. Li, S. Moser, F. Widner (postdocs), S. Murtaza (ÖAD

guest scientist), T. Erhart, C. Kieninger C. Meisenbichler,

M. Scherl, C. Vergeiner, St. Vergeiner (Ph.D. students), C.

Brenig, M. Huber, J. Mayr, P. Moser, S. Schatz, P. Singe-

wald (diploma students), M. Schäfer (master student),

G. Scherzer (chemo-technician).

>> Goal: To gain knowledge on the chemistry, on biological roles and

bio-molecular interactions of the porphyrinoid ‘pigments of life’, and

to apply this in biology and medicine.

>> Background: A large part of our research concerns the ‘pigments of

life’, which have crucial and diverse roles in cells, e.g. as cofactors in

enzymes, in biological processes driven by solar light and as metabolites

regulating expression of genes. They comprise the porphyrinoids

(heme, chlorophyll, and corrinoids) and linear tetrapyrroles, which

result from breakdown of heme and of chlorophyll. Porphyrinoids owe

their important roles in Nature to their unique molecular properties

and some of their basic structures are assumed to have pre-biotic origin.

Frequently they are functional complements to biological macro-

molecules, as coenzymes or as structuring and regulating ligands, e.g.,

in riboswitches. Our approach is geared at providing chemical insights

for the natural biological roles of the ‘porphyrinoid pigments of life’, as

well as at exploring their effects in important cellular processes.

>> Research Highlights and Outlook:Our lab has made key contributions

to the chemistry of vitamin B12-derivatives, in particular as part of

our recent program on ‘antivitamins B12’, metabolically inert B12-

derivatives. This research will help us learn more about mechanisms

of B12-dependent metabolic processes in microorganisms, animals and

humans, and in looking at still enigmatic effects of B12-deficiency by B12-

chemical biological approaches. In this context, we have developed a

synthetic approach towards a group of B12-mimics that contain transition

metals other than the B12’s own cobalt (Figure 1). A combination of

biological and chemical total synthesis was established. A first example

was AdoRhbl, the unnatural rhodium analogue of coenzyme B12. Its

Figure 1: Natural Vitamin B12-derivatives are intimately as-

sociated with their cobalt-center (the element cobalt was

named by German miners as the undesirable contamination

put into various ores by a mine ‘Kobold’).

Figure 3: 2D Localization and identification of a chlorophyll

degradation product in senescent leaves of fern using MAL-

DI-TOF mass spectrometry imaging.

Figure 2: Phyllochromobilins, the colored catabolites of chlo-

rophyll, are components of the fall colors in the leaves of de-

ciduous tree


>> Goal: The focus of our work lies on the characterization of key

features of biomolecular recognition by employing a wide range of

state of the art computational methods and developing new methods

to extract and profile key traits of biomolecules.

>> Background: Molecular recognition is a vital aspect of nearly all

biological processes, however, understanding them on a microscopical

level is not trivial. One of the most important findings of the last few

decades is the fact that biomolecules cannot be described as a static

entity. In other words, looking at a single static crystal structure is not

enough to understand the biological mechanisms of a molecule. The

studying of the dynamics of the protein and describing it as a structural

ensemble is essential for understanding the proteins’ characteristics

and functions.

The use of theoretical methods such as molecular modelling, molecular

dynamics or docking has become more and more important in the past.

It has long passed from being solely supplemental to experiments to an

Klaus R. Liedl and Daniela Schuster

>> Department of General, Inorganic and Theoretical Chemistry

Research summary

independent research field. It not only enables a better understanding

of experimental findings, but also creates insights in macromolecular

properties inaccessible to experiments.

>> Research Highlights and Outlook: Hydrophobicity plays a key role

in biomolecular recognition processes. Although there are various

experimental and theoretical techniques which are widely used, they

provide only little information about water dynamics and entropic

effects. We developed a new metric which derives spatial hydrophobicity

values directly from the dynamics of the water molecules in molecular

dynamics simulations.

Classical molecular dynamics simulations are currently restricted to the

nanosecond to microsecond timescale because of hardware limitations.

Most of the available enhanced sampling techniques use a biased potential

energy function, which makes it difficult to extract dynamical properties

of the unbiased ensemble. Following up on our previously presented

metric of the dihedral entropies we developed a metric which allows

us to obtain reweighted dihedral entropies from accelerated molecular

dynamics simulations. Thus, we can capture dynamics happening on the

millisecond timescale with microsecond long simulations.

In close collaboration with the Tollinger group as well as the lab

of Richard Weiss at the University of Salzburg we focus on the

characterization of the dynamical properties of plant pollen allergens.

Employing our previously presented dihedral entropy metric, we were

able to link molecular flexibilities of the major birch pollen allergen Bet

v 1a, captured with molecular dynamics simulations, to experimental

thermal and proteolytic stabilities. We currently investigate these

dynamics on extended timescales using our aforementioned metric of

calculating reweighted dihedral entropies from accelerated molecular

dynamics simulations.

>> Research GrantsFWF P26997, FWF P30565, FWF P30737, FWF P26782,

FFG Bridge EARLYSNOW, FWF/TWF Lise-Meitner grant

Maren Podewitz, ÖAW DOC/Birgit Waldner, ÖAD

FR9/2017, ÖAD ICM-2017-07338 grant to Navista Sri

Octa Ujiantari, CAPES Science Without Borders, bmwfw

PRIZE prototype grant, Boehringer Ingelheim

>> CoworkersMaren Podewitz, Michael Schauperl, Veronika Temml

(postdocs), Stefania Monteleone, Wang Yin, Birgit

Waldner, Anna S. Kamenik, Johannes R. Löffler, Ursula

Kahler, Monica Fernandez Quintero, Johannes Kraml,

Florian Hofer, Muhammad Akram, Sonja Herdlinger,

Fabian Mayr, Navista Sri Octa Ujiantari (Ph.D. students),

Emanuel Ehmki, Melanie Wachter, Franz Waibl, Radu

Talmazan, Dennis Dinu, Theresa Steinacher, Elisabeth

Vorhofer, Erika Strieder, Ralph Kandel, Sandra Wagner,

Christian Vieider, Alois Dalkner (MSc. Students), Alexan-

der Spinn, Lisa Retter (system administrator)


Protein dynamics and biomolecular recognition


Developmental biology

Dirk Meyer and Pia Aanstad

>> Goal: To understand molecular mechanisms underlying regulation

and coordination of fate specification, differentiation, proliferation

and migration in vertebrate embryogenesis and regeneration, with a

focus on gastrulation and pancreas formation.

>> Background: Development of endodermal organs such as the pancreas

requires complex and still poorly understood interactions of signaling

pathways in order to guarantee the temporary and spatially correct

coordination of cell proliferation, migration and differentiation. In our

research we study three specific aspects of endoderm formation by applying

genetics, molecular and in vivo imaging approaches in zebrafish: (1) the

functions of TGF-beta regulated transcription factors in early endodermal

induction, (2) the role and regulation of Hedgehog (Hh) signaling in

endodermal patterning, cell proliferation and cell migration and (3) the

molecular mechanisms underlying pancreatic islet cell formation and

maturation during embryonic development and regeneration.

>> Research Highlights and Outlook: Hh-signaling: In collaboration

with Eduard Stefan (Biochemistry) we showed that the orphan receptor

Gpr161 localises the Hh-signalling inhibitor PKA to the primary cilium,

the main site of Hh signal transduction.

>> Department of Molecular Biology

Research summary

Pancreatic regeneration: We established new tools for efficient

conditional pancreatic cell ablation in zebrafish. Using these tools we

identified a novel precursor population for acinar cell regeneration and

in collaboration with Stefan Kubicek (CeMM,/Vienna) we determined

activities of the malaria drug artemether on improved beta-cell

regeneration.

Islet development: High resolution imaging of emerging endocrine cells

revealed until now unappreciated dynamic motility. By applying novel

quantitative assays, we determined that this motility is regulated by

PI3K and GPCR signaling, and is important for islet formation.

Diabetes genes: Work on zebrafish homologs of the neonatal diabetes

and sacral agenesis gene MNX1 revealed irx1 as a direct Mnx target

and a requirement for Mnx/Irx interaction in kidney formation. Further

investigations make use of our recently established pdx1 and mnx1

zebrafish mutants as diabetes model to uncover mechanisms behind

long-term deleterious effects of hyperglycemia. In international

collaborative studies, we are defining the progression and mechanisms

of diabetes-induced effects on tissue damage and on regeneration

capacities.

>> Research GrantsFWF P25659, FWF P27338, FWF P30038, TWF 236277,

DOC 24701

>> CoworkersRobin Kimmel (Assistant Professor); Patrick Fischer,

Armin Wilfinger (postdoc); Julia Freudenblum, Réka

Lorincz, Dominik Regele, Nicole Schmitner, Philipp

Tschaikner, Onur Temocin (Ph.D. Students), Greta

Ebnicher, Gerald Lerchbaumer, Fabian Martin (master

students); Eve Holtorf, Dzenana Tufegdzic, Sonja Töch-

terle (technician)


Ronald Micura

>> Goal: To obtain an integrated understanding of RNA modifi cation

and RNA mediated regula tion and catalysis.

>> Background: For many years it was believed that there were only

a small number of non-protein-coding RNAs (ncRNAs) and that

they (tRNAs, rRNAs, spliceosomal RNAs) were involved primarily in

assembling the predominant protein macromolecules. Even large RNA

classes, such as snoRNAs and microRNAs, remained undetected. In

recent years, it became apparent that ncRNAs are numerous and that

their cellular functions – on their own or in complex with proteins – are

diverse and important. Our lab aims at a comprehensive molecular

understanding of cellular processes involving ncRNAs, in particular of

gene regulation by riboswitches but also of traditional ncRNAs such

as encountered during ribosomal translation. Our lab has a major

focus on the chemical synthesis of RNA allowing the introduction of

site-specific modifications, naturally occurring and artificial ones. This

enables us to evaluate their structure and function by a great diversity

of chemical and biophysical methods, with a focus on chemical and

biochemical probing techniques, fluorescence spectroscopy (including

single molecule imaging), NMR spectroscopy, and X-ray crystallography.

>> Research Highlights and Outlook: The discovery of four novel self-

cleaving ribozyme classes in the years 2014 and 2015 has opened a unique

opportunity to undertake structure-function studies to comparatively

assess the architectural diversity, catalytic cores and mechanism of

action. To this end, we have provided insights into the topological


Research summary

constraints contributing to catalysis of these ribozymes by chemical,

structural, and biochemical studies. One of the new self-cleaving RNAs

contains the so-called pistol motif revealed by comparative genomic

analysis; its precise biological function is yet unknown. Our recent

crystal structure of a pre-catalytic state of this RNA shows guanosine

G40 and adenosine A32 close to the G53–U54 cleavage site (see

graphics a). While the N1 of G40 is within 3.4 Å of the G53 2’-OH group

that attacks the scissile phosphate (see graphics b), thus suggesting

a direct role in general acid–base catalysis, the function of A32 was

less clear. We found evidence from atom-specific mutagenesis that

neither the N1 nor N3 base positions of A32 are involved in catalysis. By

contrast, the ribose 2’-OH of A32 turned out to be crucial for the proper

positioning of G40 through a H-bond network that involves G42 as a

bridging unit between A32 and G40. We also found that disruption of

the inner-sphere coordination of the active-site Mg2+ cation to N7 of

G33 makes the ribozyme drastically slower. A mechanistic scenario with

A32 playing a major structural role and hydrated Mg2+ playing a major

catalytic role in cleavage, was therefore disclosed.

Another aim of our lab is to understand the functional roles of RNA

in the cell. Consequently, it is essential to elucidate the dynamics of

their production, processing and decay. A recent method for assessing

mRNA dynamics is metabolic labeling with 4-thiouridine (4sU), followed

by thio-selective attachment of affinity tags. Detection of labeled

transcripts by affinity purification and hybridization to microarrays or

by deep sequencing then reveals RNA expression levels. Our own efforts

focused on the development of a novel sequencing method (TUC-seq)

that eliminates affinity purification and allows for direct assessment

of 4sU-labeled RNA. It employs an OsO4-mediated transformation to

convert 4sU into cytosine. We exemplified the utility of the new method

for verification of endogenous 4sU in tRNAs and for the detection of

pulse-labeled mRNA of seven selected genes in mammalian cells to

determine the relative abundance of the new transcripts. The results

prove TUC-seq as a straight-forward and highly versatile method for

studies of cellular RNA dynamics.

Finally, the continuous development of synthetic methods for efficient

access to chemically modified RNA with novel functional properties is in

the center of our research interests.

>> Research GrantsFWF (I1040, P27947), SNF (Early Postdoc.Mobility), FFG

(West-Austrian BioNMR)

>> CoworkersJennifer Gebetsberger, Thomas Amort (postdocs);

Marina Frener, Lukas Jud, Sandro Neuner, Christian

Riml, Nikola Vušurović, Catherina Gasser, Elisabeth

Fuchs, Elisabeth Mairhofer, Christoph Falschlunger, Eva

Neuner, Josef Leiter, Maximilian Himmelstoß (Ph.D.);

Daniel Fellner (technician)

Synthesis, structure, and function of non-coding RNAs


Cell physiology and gene regulation

Bernd Pelster, Adolf Sandbichler, Thorsten Schwerte

>> Goal: Our research aims at the analysis of molecular and structural

mechanisms as well as genetic control pathways of physiological

phenomena.

>> Background: The adaptation of animals to changing environmental

conditions includes adaptations at the cellular and molecular level in

order to maintain homeostasis of energy metabolism, ion regulation

and acid base balance. Changing oxygen partial pressures, variable light

regimes or exposure to toxicants, for example, are readily perceived by

animals of different developmental stage. In our work we focus on the

large scale changes in the overall gene expression patterns induced by

these environmental perturbations, typically resulting in characteristic

modifications in metabolic defense reactions, activity patterns, oxygen

transport capacities and overall metabolic or ion regulatory activity. Of

particular interest are the control mechanisms guiding these expression

changes at the transcriptional and translational level. The sophisticated

interconnection and interaction between the different regulatory

pathways is addressed using appropriate invertebrate and vertebrate

model animals. The data, obtained at the cellular, molecular and organ

level, are discussed with respect to the possible adaptational benefit for

the whole organism.

>> Research Highlights and Outlook: The mutant line POPDC1S201F of

the zebrafish is characterized by muscular dystrophy and arrhythmia

Abb. 2: Cadmium exposure leads to phosphorylation of ATF and an increased expression of wMT-

2. The expression of wMT-2 is, however, suppressed when Cd-exposed earthworms are in addition

injured.


Research summary

by affecting protein trafficking. Characterization of the phenotype of

this mutant showed that it could be a disease model for the analysis of

the genetic background for muscular dystrophy and heart dysfunction.

In our research focusing on cellular redox balance and it‘s role in

circadian timekeeping and hypoxia stress response we established the

use of new and improved fluorescent protein sensors enabling us to

measure the redox balance in different cellular organelles and their

contribution to whole cell redox equilibrium. The cell physiological

consequences of redox alterations and their effect on cellular oxygen

consumption and glycolytic metabolism are being addressed.

Our studies demonstrated that remote levels of heavy metal stress

already cause epigenetic changes in earthworms, which persist even

after the stressor has long disappeared. Moreover, we were able to

reveal that wound repair suppresses specific detoxification mechanisms,

which might demonstrate a link between stress response and immunity.

During the spawning migration the European eel is exposed to extreme

hydrostatic pressures, and in a process named silvering eels prepare for

this migration. Silvering encompasses significant modifications at the

transcriptional level in swimbladder tissue to adjust gas permeability,

metabolism and ion transport capacities to elevated hydrostatic

pressure. Infection of the swimbladder with the nematode Anguillicola

crassus significantly impairs these silvering induced changes in

swimbladder tissue, which may compromise the spawning migration.

By an improved sequencing the genome assembly for the European eel

could be significantly improved.

>> Research GrantsFWF P26363-B25; FWF I2984-B25; §27 Projekt DB-Nr:

215529; Nachwuchsförderung Projekt Nr.: 226115;

Förderung des Vizerektorats für Forschung Nr.: 235916;

Lise Meitner (M2262-BBL)

>> CoworkersMartina Höckner (Associate Professor); Birgit Fiechtner,

Bettina Peer (technicians); Maja Šrut, Gabriel

Schneebauer, Sigrid Zobl (postdocs); Victoria Drechsel

(PhD student)

Abb. 1: (Top) Anguillicola crassus, ~70 parasites of a single

swimbladder in a 90 mm petri dish; European eel with

position of the swimbladder (red), (Middle) swimbladder;

scale bar represents 10 mm, (Bottom) Enzymes and

metabolites (blue) involved in ROS detoxification in gas

gland cells to avoid various oxidative damages (red);

superoxide dismutase (SOD), glutathione peroxidase (GPx),

glutathione reductase (GR), reduced glutathione (GSH),

oxidized glutathione (GSSG), malondialdehyde (MDA).


Structure-functional activity relationship investigations on ligands interacting with opioid receptors

Helmut Schmidhammer and Mariana Spetea

>> Goal: To perform basic and applied research as theoretical and ex-

perimental work in order to advance the current understanding on

structure-functional activity relationships for ligands interacting with

opioid receptors.

>> Background: The kappa opioid receptor (KOR) and its endogenous

ligand, dynorphin, have received major attention in past years due to

their involvement in a variety of physiological and behavioral responses

(i.e. pain, stress, motivation, emotion, cognition, reward). Dysregulation

of the KOR/dynorphin system is responsible for the development and

maintenance of neuropsychiatric conditions (Figure 1A). Preclinical

and clinical evidence indicates that this system contributes to symptom

clusters that are shared by many neuropsychiatric disorders, and thus

to their comorbidity (Figure 1A). Differential modulation of the KOR

is regarded as a promising strategy for developing therapies for pain,

drug addiction, mood disorders, neurological conditions, and itching

skin diseases by either activating or blocking the receptor (Figure 1B).

Although KOR activation does not produce dependence, euphoria, or

leads to respiratory suppression, it induces dysphoria, sedation and

psychotomimesis. The concept of biased signaling has come forward

with the realization that the KOR activates G protein-dependent and

independent signaling networks. Biased ligands can alter the linkage


Research summary

between G protein-dependent (responsible for beneficial effects, e.g.

analgesia) and β-arrestin2-dependent (responsible for adverse effects)

pathways with important therapeutic implications.

>> Research Highlights and Outlook: Our research group has generated

new KOR ligands as small molecules featuring a diphenethylamine

scaffold (Figure 1C). Multidisciplinary, synergistic approaches ranging

from molecular in silico and in vitro levels to in vivo systems were

combined by linking bioinformatics and computational systems

with biochemical, pharmacological and disease animal models. Our

lab established for the new KOR ligands: (i) a KOR target-oriented

pharmacological profile (high affinity, selectivity, full/partial agonism

or antagonism at the KOR, and biased signaling towards G protein

activation), (ii) antinociceptive efficacy in thermal nociceptive and

visceral mouse pain models, (iii) antiseizure efficacy in prodynorphin-

knockout mice, (iv) anticonvulsant efficacy in a mouse model of

temporal lobe epilepsy, and (v) reduced propensity for unwanted

behavioral and side effects (i.e. aversion, sedation, motor dysfunction).

Structural, molecular and functional mechanisms that can form the

basis for such an improvement of the benefit/risk index were analyzed

in detail. The emerged findings underline the strong potential of the

developed KOR ligands as new and improved therapeutics for human

diseases. Furthermore, the emerged G protein biased KOR ligands

may be exploited for use as research tools for understanding the basic

biology of KOR signaling, and most important to have a tremendous

prospective for innovative drug discovery strategies.

>> Research GrantsFWF I2463, FWF P30430, TWF UNI-0404/1596 (TWF),

Aktion D. Swarovski KG 2014 P7400-029-011, ÖAD-WTZ

FR12/2016.

>> CoworkersAquilino Lantero, Stefan Noha (postdocs); Filippo

Erli, Maria Dumitrascuta (Ph.D. students); Michael

Mairegger, Andreas Ritsch, Lea Schläfer, Birgit

Steinkellner, Dominik Bucher, Katja Walker, Lisa-Marie

Watzke (diploma students)

Figure 1: The KOR is a key target for developing pharmacotherapies for neuropsychiatric disorders.

(A) Dysfunction of the KOR/dynorphin system is responsible for the development of neuropsychiatric

disorders and their comorbidity. (B) Differential modulation (activation or inhibition) of the

KOR is regarded as a promising strategy for developing therapies for pain, addiction, mood and

neurological disorders. (C) Generation of a new class of KOR ligands as small molecules featuring

a diphenethylamine scaffold, which evolved as G protein KOR biased agonists, partial agonists and

antagonists.


Rainer Schneider and Bernhard Auer

>> Department of Biochemistry

>> Goal: We are studying targeted proteolysis in a wide range of aspects

from the human ubiquitin system to specific directed evolution of

proteases for the development and production of drugs to treat human

diseases.

>> Background: One of our main research fields covers the structure

and functions of the MID1 protein complex, an important player in the

regulation of phosphorylation and translational control. The ubiquitin

ligase MID1 targets the catalytic subunit of Protein Phosphatase 2A

(PP2A) for proteolytic degradation. Lack of human MID1 causes Opitz

syndrome (midline defect with cognitive impairment). Furthermore

MID1 has an impact on mTOR signaling, alterations of which are

involved in several intellectual disability and epilepsy syndromes. As

we are also involved in a study on a novel, potentially mTOR-related

epilepsy syndrome caused by a protease-mutation found in a family

in Tyrol, we are interested to study the impact mTOR exerts on the

local protein homeostasis in hippocampal synaptosomes of mice models

reflecting such mTOR-related syndromes and how this process might be

regulated by specific protease activities.

Additionally, we are engaged in the development of biotechnological

tools namely novel proteases to improve the biotechnological

production of biogenic drugs.

>> Research Highlights and Outlook: With our central research on the

structure and function of the MID1 complex and the study of movement

disorder diseases as well as with our biotechnological/bioinformatic

approaches we achieved several major goals:

a) After we had identified MID1 as an important player in the

development of prostate cancer together with groups from the Medical

University of Innsbruck, Berlin, Bonn and Dundee, we were able to

identify small substance modulators of MID1 which are potential new

drugs that could interfere with cancer and neurodegeneration.

We found a potential anti prostate cancer drug that ablates the

translation enhancing effect of MID1 on AR-mRNA, namely Metformin,

which is a safe drug that is used extensively since 60 years to treat

type 2 diabetes mellitus. Our finding provides an explanation for the

recently found inverse correlation between Metformin-treatment and

cancer incidence.

In further searches for small substances targeting the MID1 complex,

we recently identified resveratrol, the famous polyphenol found in

red wine, as an inhibitor of the MID1-pathway that can trigger the

dephosphorylation of hyperphosphorylated tau as found in Alzheimer´s

disease. This finding was achieved in cooperations with the groups of

Sybille Krauss at the DZNE in Bonn and Susann Schweiger in Mainz (1).

Together with an EU-consortium (ERANET NEURON) including groups

from Milan, Berlin and Mainz we are studying several syndromes that

are associated with altered MID1/mTOR signaling and present with

epilepsy and/or intellectual disabilities. Together with the proteomics

platform from the Medical University of Innsbruck (Lindner group)

we try to elucidate altered expression profiles of hippocampal

synaptosomes from different MID1- , TSC2- and Rett-syndrome mouse

models to decipher the impact of mTOR in these diseases.

Furthermore, in cooperation with the department of Neurology at the

Medical University of Innsbruck we are engaged in several research

projects concerning movement disorder diseases. In a Tyrolian case

of myoclonus epilepsy we were now able to identify the respective

mutated gene, a protease which seems to influence mTOR signaling,

thus connecting another epilepsy syndrome with this pathway.

b) Under the framework of the Austrian Center of Industrial

Biotechnology (ACIB) we are working successfully on several projects

(strategic projects and company projects) in which we are developing

novel biotechnological tools for up- and downstream processing (2,

patents pending).

c) Additionally, we are using bioinformatic approaches to understand

the structure/function/evolution relationships between proteins. In this

respect we are analyzing highly variable viral proteins (Coronaviruses)

and peptides that modulate the immune system like Thymulin (3).

>> Research GrantsFWF-TRP002330, FFG-ACIB(K2) P25.081 (Company

Project), FFG-ACIB P25.111 (Strategic Project), EFACTS-

EU242193, FWF- I 1570-B13 (ERANET NEURON), MFF253

>> CoworkersRainer Schneider (Project leader), Sandra Pfurtscheller,

Kamil Rolski, Petra Engele, Christina Kröß, Alexander

Mödlhammer, Kevin Vince (PhD students), Simon Hofer,

Stefan Felderer, Bernhard Sprenger (diploma students)

Figure 1: MID1 is a modulator of PP2Ac influencing several

major players and pathways

Targeted proteolysis in human diseases and its impact on drug development and production


Cell signaling in chronic CNS disorders

Nicolas Singewald, Alexandra Koschak and Jörg Striessnig

The major research areas of the CMBI project leaders in the Department of

Pharmacology and Toxicology the pathophysiology of neuropsychiatric

disorders (in particular fear, anxiety, autism spectrum disorders and

Parkinson’s Disease), retinal disorders and endocrine disease (such as

primary hyperaldosteronism and diabetes mellitus). Most of this work

is embedded in the FWF-funded Spezialforschungsbereich SFB F44 “Cell

signaling in chronic CNS disorders” (2011-2019), the doctoral programs

Molecular Cell Biology and Oncology (MCBO, 2005-2018), Signal

Processing in Neurons (SPIN), the recently approved doc.funds network

“CavX” and a European Training Network.

Neuropharmacology group (N. Singewald)

>> Goal: Our main aim is to identify novel drug targets that facilitate

anxiety- and fear inhibitory mechanisms, including fear extinction, to

guide improved treatment strategies for different forms of anxiety

disorders, which are the most prevalent of all mental disorders.

>> Background: Effective long-term treatment for fear and anxiety-

related disorders is a continuing challenge. One emerging treatment

strategy is combining exposure-based cognitive behavioral therapy with

extinction-facilitating drugs. Current research identified facilitation of

dopaminergic signaling and/or modulation of epigenetic mechanism,

in particular histone deacetylases and microRNAs, as means to boost

and normalize aberrant fear-inhibitory learning, which is common in

human anxiety disorders.

>> Research Highlights and Outlook: On the basis of these results we

are now gaining detailed insight into which dopamine receptors and

brain region(s) mediate the normalization of impaired fear extinction

learning by using pharmacological, optogenetic and chemogenetic

approaches. One of our prominent findings was that the microRNA

mir-144 is involved in orchestrating the rescue of impaired extinction

learning. We are currently establishing whether this and other

microRNAs can be used as bio-markers/novel therapeutic targets for

the treatment of anxiety disorders. In addition, we aim to improve the

tolerability of exposure based therapy by novel non-sedative anxiolytic

drugs which do not impair extinction learning. Neuropeptide S (NPS)

is one such promising candidate. We currently pursue identification

of NPS-receptor agonists by virtual screening and in-vitro studies in

collaboration with CMBI groups of H. Stuppner, D. Schuster and R. Gust.

>> Department of Pharmacy, Pharmacology and Toxicology

Research summary

>> Research GrantsFWF SFB-F4401, FWF SFB-F4402, FWF SFB-F4410,

FWF P24785, FWF P25014, FWF P25375, FWF

W1101, FWF W1206, FWF P26881, FWF P27809,

FWF I2433, ITN Horizon 2020 “switchboard”, Tiroler

Wissenschaftsförderung (TWF) ZAP740036, Univ. of

Innsbruck (FLD #242170, #194449, #217264, #214976),

County of Tyrol (FLD #225100, #152787), H. Lundbeck

A/S, FWF P27852, FWF P28146, FWF I02215

>> Scientific coworkers (2016/2017)Petronel Tuluc, Thomas Fenzl, Alexandra Pinggera,

Nadja Hofer, Nadine J Ortner, Kathrin Kähler, Hartwig

Seitter, Karl Ebner, Maria Kharitonova, Simone Sartori,

Anupam Sah, Conor Murphy, Verena Maurer, Thomas

Keil, Veronica Fontebasso, Sinead Rooney, Michael

Oberhauser, Lucia Zanetti, Irem Kilicarslan, Anita Siller,

Eva Maria Fritz, Joseph Moreno Rius

Molecular Pharmacology group (J. Striessnig)

>> Goal: This group tries to better understand the physiological and

pathophysiological role of voltage gated Ca2+ channels (VGCCs) in

human disease. Recently, a major focus was on autism spectrum

disorders (ASD) and Parkinson’s Disease (PD).

>> Background: Excessive Ca2+ signalling can be harmful for cell function

and survival. We have recently found that excessive cellular Ca2+ entry

into neurons through voltage-gated Ca2+ channels may also cause CNS

diseases, such as migraine or autism.

>> Research Highlights and Outlook: We have characterized sporadic

mutations in the CACNA1D gene in patients with autism with our

without neurological disorders, such as epilepsy. From six such mutations

in seven patients we now learned that all cause characteristic gating

changes of the channel that allow enhanced Ca2+ entry in neurons.

Although only few patients with these mutations are described, Ca2+

channel blockers may be useful to prevent excessive signalling. We

therefore tested if clinically used Ca2+ channel blockers inhibit these

(so-called Cav1.3 L-type) calcium channels during simulated neuronal

activity (Figure). Our experiments suggest that the required therapeutic

dose would be slightly higher than for blood pressure lowering. This

hypothesis is now tested in a new animal model containing one of

these mutations.

Molecular sensory physiology (A. Koschak)

>> Goal: Mapping the role of L-type calcium channels in retinal diseases.

>> Background: In photoreceptors Cav1.4 L-type calcium channels

(LTCCs) serve as the predominant source for Ca2+ entry to allow sustained

release of glutamate at their synaptic sites. Mutations in the encoding

CACNA1F gene have been associated with a number of human retinal

diseases, such as congenital stationary night blindness type 2 (CSNB2).

>> Research Highlights and Outlook: We investigate mice carrying a

CSNB2 mutation which reproduces the functional phenotype described

in a family with the corresponding mutation. We showed that similar

to human CSNB2 both rod and cone signaling pathways are affected.

We demonstrated a defect in neuronal wiring in diseased mice evident

as formation of aberrant synaptic contacts and show remodeling of

second order neurons. We currently investigate if Cav1.4 might also

be functionally relevant also in bipolar cells by generating cell-type

specific Cav1.4 knock out mice.

Figure: The Figure shows Ca2+ inward current through

Cav1.3 L-type Ca2+ channels (stably expressed in HEK-293

cells) during electrical activity simulating the continuous

activity of a dopamine neuron in the substantia nigra of

the midbrain. We tested if isradipine, a Ca2+ channel blocker

currently clinically used as antihypertensive, can inhibit

these channels at nanomolar concentrations (20 nM, 3 µM).

Inhibition of Cav1.3 channels occurred with IC50 values in the

low nanomolar range that should allow the in vivo inhibition

of these channels by very high therapeutic doses of this drug

in patients.


Pharmacognosy – combining traditional knowledge with innovation

Markus Ganzera and Hermann Stuppner

>> Goal: Based on the traditional use of medicinal plants from around

the globe, modern approaches concerning the identification and bioac-

tivity of therein found natural products, their analysis in crude drugs,

products or biological samples by innovative techniques, and the use of

in-silico activity prediction tools are the main targets of research.

>> Background: It is more likely that natural products show bioactivity,

because their biosynthesis proceeds with sequential binding of the

biosynthetic intermediates to different proteins. Thus, they are

promising leads for drug discovery, and not surprisingly the vast majority

of commercial drugs actually derive from them. Pharmacognosy, which

focuses on the study of medicinal drugs derived from plants, has

evolved from its classical, microscopy based origin to a modern and

interdisciplinary area of research within the last decades. Today the

covered topics range from the isolation and structural characterization

of natural products, to the development of analytical tools for

their qualitative and quantitative assessment, studies investigating

metabolism or pharmacological properties by conventional or

computer based approaches, or ecologically relevant questions. At

the Department of Pharmacy / Pharmacognosy all of these aspects

are covered and numerous publications as well as many successfully

conducted research projects indicate an outstanding position in natural

products research. Experienced staff scientists, motivated PhD students

and a broad range of available equipment (LC-MS, GC-MS, CE-MS, LC-

NMR, SFC-MS, 3D-databases, etc.) are the reason for this situation.

>> Research Highlights and Outlook: One main target of research is the

evaluation of alternative, innovative techniques for natural products

analysis. Supercritical Fluid Chromatography (SFC) showed to be an

interesting option, as for example the first successful separation

of coumarins in Angelica dahurica and Ammi visnaga, or that of six

lactones in Piper methysticum (fig. 1) could be achieved. All methods

impress with extremely fast separations in the range of a few minutes

only. In an FWF funded project, novel stationary phases for Capillary

Electrochromatography (CEC) are evaluated. In cooperation with the

Department for Analytical Chemistry and Radiochemistry, an innovative

zwitterionic monolithic phase was developed and applied for the

>> Department of Pharmacy, Pharmacognosy

Research summary

>> Research GrantsFWF P296710, FWF P293050, FWF P26917, FWF P24168,

FWF T942, FFG Alpine Kosmezeutika P7400-012-048, FFG

VASCage P7400-012-047, BMWF P7400-012-052, EU-FP7

IAPP – NATPROTEC P7400-012-037, EU H2020-MSCA-RISE

- MediHealth P7400-012-049, EUREGIO ZFIPN000550,

EUREGIO ZFIPN000310

>> CoworkersStefan Schwaiger, Sonja Sturm, Birgit Waltenberger

(research associates); Anja Hartmann, Bianka Siewert,

Veronika Temml (postdocs); Nora Engels, Gibitz-Eisath

Nora, Gratl Verena, Stefanie Hofer, Stefan Loos, Fabian

Mayr, Simon Moosmang, Adele Murauer, Benjamin

Mutschlechner, Maria Orfanoudaki, Luca Pompermaier,

Silvia Revoltella (Ph.D. students)

quantitative determination of several phenolic acids in coffee beans.

Two aspects render this study noteworthy: first, the unique chemical

composition / structure of the monolith and second, the fact that CEC

has barely been used for the analysis of small molecules.

Another focus is the discovery of bioactive natural products by

activity guided isolation. Recent examples are investigations on the

proanthocyanidin fraction of Ephedra sinica, which is able to significantly

inhibit XIAP (X-linked inhibitor of apoptosis protein), or the identification

of anti-inflammatory compounds (i.e. benzofuranes, fig. 2) in the roots of

Doronicum austriacum. In particular, 6,12-dihydroxy-(−)-2S-tremetone (1)

showed the highest activity in the performed experiments and reduced

ROS (reactive oxygen species) production in macrophages at 10 µM by

approximately 50%. Comparable results were observed for nitric oxide-

release and iNOS (inducible nitric oxide synthase) expression.

In order to permit a comprehensive insight in our metabolome and

to monitor small differences caused by diseases, lifestyle or nutrition,

highly sophisticated, selective, and sensitive analytical techniques like

(U)HPLC-QToF-MS or NMR spectroscopy in combination with powerful

multivariate statistical tools such as PCA or OPLS-DA are applied. Within

an ongoing FFG funded K-project “VASCage – Gut, Diet, Microbiota

and Vascular Ageing” we work on the establishment and validation

of improved sample preparation protocols for the body fluids

urine, serum and feces (fig. 3). They are evaluated using the above

mentioned analytical and statistical techniques, and permit a conclusive

identification of diverse biomarkers.

Since 2016, we are also coordinating the project “MediHealth – Novel

natural products for healthy ageing from Mediterranean diet and food

plants of other global sources”, which is funded by the Commission

of the European Community (Research and Innovation Staff Exchange

(RISE), Marie Curie Actions). The project is based on a well-balanced

exchange of researchers between 5 universities and 4 companies

from European countries as well as 4 universities from non-European

countries. The main goal of the MediHealth project (http://medihealth.

eu/) is to introduce a novel approach for the discovery of active

agents of food plants from the Mediterranean diet and other global

sources to promote healthy ageing. To achieve this goal, plants from

the Mediterranean diet and edible plants from Africa, Asia and South

America have been carefully selected and subjected to in silico, in vitro,

in vivo and metabolism analysis. Bioactive plant constituents will be

isolated and identified. Pharmacological profiling of bioactive natural

products as well as identification and synthesis of their metabolites will

be carried out. Finally, process optimization studies will be performed

to develop innovative nutraceuticals, dietary supplements or herbal

medicinal products.

Figure 1: Separation of six lactones in Piper methysticum

roots by SFC. Murauer, A., Ganzera, M. Planta Med. 2017, 83,

1053-1057, doi: 10.1055/s-0043-100632.

Figure 2: DC separation and structures of bioactive

compounds isolated from the roots of Doronicum

austriacum. Marzocco, S., Adesso, S., Alilou, M., Stupppner,

H., Schwaiger, S. Molecules 2017, 22/6, Nr. 1003, doi: 10.3390/

molecules22061003.

Figure 3: Results of NMR studies indicating that directly

prepared human feces extracts (orange) provide more

reproducible results than those obtained with multi step

procedures (blue). Moosmang, S., Pitscheider, M., Sturm, S.,

Seger, C., Tilg, H., Halabalaki, M., Stuppner H. Clin. Chim.

Acta. In press, doi: 10.1016/j.cca.2017.10.029.


Biomolecular NMR spectroscopy

Martin Tollinger and Christoph Kreutz

>> Goal: The experimental characterization of structure, dynamics and

function of proteins and (ribo)nucleic acids.

>> Background: It has become increasingly clear in the last decade that

the three-dimensional structures of proteins and (ribo)nucleic acids

are generally flexible. Typically, these biomolecules adapt a defined

distribution of structures around the „ground state“ that is obtained

by standard structure determination protocols. Structural flexibility

is required for the biological function of a biomolecule per se. For

example, recognition and binding of bioactive ligands, catalysis of

enzymatic reactions, regulation of enzymatic turnover and processing

of allosteric information all rely on structural flexibility. In our group we

aim at measuring and understanding structural flexibility of proteins

and (ribo)nucleic acids at atomic resolution using NMR spectroscopy.

We determine solution structures by standard NMR techniques and

complement these data by NMR relaxation measurements to provide a

genuine description of how these molecules function. We specifically

focus on the mechanisms of ligand recognition and binding, protein

and RNA folding and stability, and enzymatic catalysis.

>> Research Highlights and Outlook: One focus at our laboratory is

the characterization of functional dynamics of (ribo)nucleic acids.

In this context, we are advancing the current protocols for isotope

(13C, 15N, 2H) labeling of DNA and RNA. This is especially important

for the application of dynamic NMR experiments, such as saturation

transfer and relaxation dispersion experiments, where simple spin

topologies are a mandatory prerequisite. For this task, we combine

chemical synthesis and NMR in a unique way. Recently, a method to

introduce isotope labeling patterns into larger RNAs comprising up

to 80 nucleotides was established in our group. We currently focus

on probing the functional dynamics of catalytically active non-coding

RNAs, such as a group II intron construct or the pistol ribozyme.

This will give unprecedented insights into the structural flexibility

underlying biological function.


Research summary

>> Research GrantsFWF-P26550, FWF-P26849, FWF-P28725, FWF-P30370,

FWF-P31054, FFG-858017, ERDF-ITAT1013, OEAW DOC

fellowship, Alpine Research Center Obergurgl

>> CoworkersL. Ahammer, V. Dietrich, R. Eidelpes, S. Führer, S.

Grutsch, M. Juen, J. Kremser, J. Ludescher, F. Nußbaumer,

R. Plangger, E. Strebitzer (Ph.D. students), K. Erharter, J.

Unterhauser (master students)

Another focus at our laboratory are allergenic proteins such as Bet

v 1, which represents the main cause for allergic responses to birch

pollen. A substantial proportion of individuals who suffer from birch

pollen allergy develop intolerance to different kinds of fruits, nuts and

vegetables due to immunologic cross-reactivity of Bet v 1-specific IgE

antibodies with homologous proteins in these kinds of food. The most

frequent cross-allergies are directed towards apples and hazelnuts. We

have recently determined the three-dimensional structure of the major

apple allergen Mal d 1 and are currently working on allergenic proteins

from hazelnut and peach. In future experiments, we are planning

to establish how naturally occurring isoforms of these proteins with

>95% sequence identity and identical three-dimensional ground state

structures can elicit different immunologic responses.

Figure 1: General work flow. Chemical synthesis is used

to introduce atom-specific stable isotope labels (e.g. 13C,

highlighted in orange) into RNA precursors. After sequence

assembly, solution NMR experiments are carried out to probe

structure and function of the target RNA.

Figure 2: Left: Three-dimensional solution NMR structure of the major apple allergen Mal d 1. This 17.5 kDa protein is responsible for allergic reactions to apples in

>70% of all birch pollen sensitized patients. Center: Fully assigned, 2-dimensional 1H15N NMR spectrum of Mal d 1. Right: Mal d 1 was first identified and isolated from

Golden Delicious and Granny Smith apples.

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Publications Publications

K. Bister, M. Hartl, E. Stefan

Stefan E, Troppmair J, Bister K. Targeting the architecture of deregu-

lated protein complexes in cancer. Adv. Protein. Chem. Struct. Biol. in

press (2018). (Published online 18 August 2017).

Gufler S, Artes B, Bielen H, Krainer I, Eder MK, Falschlunger J, Bollmann

A, Ostermann T, Valovka T, Hartl M, Bister K, Technau U, Hobmayer B.

β-Catenin acts in a position-independent regeneration response in the

simple eumetazoan Hydra. Dev. Biol. 433, 310-323 (2018). (Published

online 3 November 2017).

Hunter E, Bister K (eds). Viruses, Genes, and Cancer - Current Topics

in Microbiology and Immunology, Vol. 407. Springer International

Publishing (2017).

Stefan E, Bister K. MYC and RAF: Key effectors in cellular signaling and

major drivers in human cancer. Curr. Top. Microbiol. Immunol. 407, 117-

151 (2017).

Raffeiner P, Schraffl A, Schwarz T, Röck R, Ledolter K, Hartl M, Konrat

R, Stefan E, Bister K. Calcium-dependent binding of Myc to calmodulin.

Oncotarget 8, 3327-3343 (2017).

Torres-Quesada O, Mayrhofer JE, Stefan E. The many faces of compart-

mentalized PKA signalosomes. Cell Signal. 37, 1-11 (2017).

Torres-Quesada O, Röck R, Stefan E. Systematic quantification of cAMP-

controlled PKA interactions. Horm. Metab. Res. 49, 240-249 (2017).

Bruystens JG, Wu J, Fortezzo A, Del Rio J, Nielsen C, Blumenthal DK,

Röck R, Stefan E, Taylor SS. Structure of a PKA RIα Recurrent Acrodys-

ostosis Mutant Explains Defective cAMP-Dependent Activation. J. Mol.

Biol. 428, 4890-4904 (2016).

Bachmann VA, Mayrhofer JE, Ilouz R, Tschaikner PM, Raffeiner P, Röck

R, Courcelles M, Apelt F, Lu T, Baillie GS, Thibault P, Aanstad P, Stelzl U,

Taylor SS, Stefan E. Gpr161 anchoring of PKA consolidates GPCR and

cAMP signaling. Proc. Natl. Acad. Sci. USA 113, 7786-7791 (2016).

Rinaldi L, Delle Donne R, Sepe M, Porpora M, Garbi C, Chiuso F, Gallo

A, Parisi S, Russo L, Bachmann V, Huber RG, Stefan E, Russo T, Feliciello

A. praja2 regulates KSR1 stability and mitogenic signaling. Cell Death

Dis. 7: e2230 (2016).

Ijaz M, Bonengel S, Zupančič O, Yaqoob M, Hartl M, Hussain S, Huck CW,

Bernkop-Schnürch A. Development of oral self nano-emulsifying delivery

system(s) of lanreotide with improved stability against presystemic thiol-

disulfide exchange reactions. Expert Opin. Drug Deliv. 13, 923-929 (2016).

Hartl M. The quest for targets executing MYC-dependent cell transfor-

mation. Front. Oncol. 6, 132 (2016).

Patents

Stefan E, Röck R, Raffeiner P, Bachmann V. Quantification of an interac-

tion between a Ras protein and a Raf protein. European Patent Office,

EP16191530.1 (2016).

Stefan E, Mayrhofer J. Full-length kinase conformation reporter. Euro-

pean Patent Office, EP16165865.3 (2016).

G. Bonn, C. Huck

Bec K, Grabska J, Ozaki Y, Huck CW. Influence of non-fundamental

modes on mid-infrared spectra anharmonic DFT study of aliphatic

ethers. J. Phys. Chem. A 121, 1412-1424 (2017).

Henn R, Kirchler CG, Grossgut ME, Huck CW. Comparison of sensitivity

to artificial spectral errors and multivariate LOD in NIR spectroscopy –

Determining the performance of miniaturizations on melamine in milk

powder. Talanta 166, 109-118 (2017).

Huck, CW. Selected latest applications of molecular spectroscopy in

natural product analysis. Phytochemistry Letters 20, 491-498 (2017).

Kirchler CG, Pezzei CK, Bec KB, Henn R, Ishigaki M, Ozaki Y, Huck CW.

Critical Evaluation of NIR and ATR-IR Spectroscopic Quantifications of

Rosmarinic Acid in Rosmarini folium Supported by Quantum Chemical

Calculations. Planta Med. 83/12/13, 1076-1084 (2017).

Murauer A, Bakry R, Schottenberger H, Huck CW, Ganzera, M. An in-

novative monolithic zwitterionic stationary phase for the separation of

phenolic acids in coffee bean extracts by capillary electrochromatogra-

phy. Anal. Chim. Acta 963, 136-142 (2017).

Jabeen F, Najam-ul-Haq M, Rainer M, Huck CW, Bonn GK. In-Tip

Lanthanum Oxide Monolith for the Enrichment of Phosphorylated

Biomolecules. Anal. Chem. 89/19, 10232-10238 (2017).

Pezzei CK, Schönbichler SA, Kirchler CG, Schmelzer J, Hussain S, Huck-

Pezzei VA, Popp M, Krolitzek J, Bonn GK, Huck CW. Application of

benchtop and portable near-infrared spectrometers for predicting the

optimum harvest time of Verbena officinalis. Talanta 169, 70-76 (2017).

Teshome DA, Rainer M, Noel JC, Schüßler G, Fuchs D, Bliem HR, Bonn

GK. Chemical compositions of traditional alcoholic beverages and con-

sumers’ characteristics, Ethiopia. African Journal of Food Science 11/7,

234-245 (2017).

K. Breuker

Vušurović J, Schneeberger EM, Breuker K. Interactions of protonated

guanidine and guanidine derivatives with multiply deprotonated RNA

probed by electrospray ionization and collisionally activated dissocia-

tion. ChemistryOpen 6, 739-750 (2017).

Kremser J, Strebitzer E, Plangger R, Juen MA, Nußbaumer F, Glasner H,

Breuker K, Kreutz C. Chemical synthesis and NMR spectroscopy of long

stable isotope labelled RNA. Chem. Commun. (Camb) 53, 12938-12941

(2017).

Skinner OS, McAnally MO, Van Duyne RP, Schatz GC, Breuker K, Comp-

ton PD, Kelleher NL. Native electron capture dissociation maps to Iron-

binding channels in horse spleen Ferritin. Anal. Chem. 89, 10711-10716

(2017).

Glasner H, Riml C, Micura R, Breuker K. Label-free, direct localization

and relative quantitation of the RNA nucleobase methylations m6A,

m5C, m3U, and m5U by top-down mass spectrometry. Nucleic Acids Res.

45, 8014-8025 (2017).

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Schneeberger EM, Breuker K. Native top-down mass spectrometry of

TAR RNA in complex with a wild-Type tat peptide for binding site map-

ping. Angew. Chem. 129, 1274-1278 (2017); Angew. Chem. Int. Ed. Engl.

56, 1254-1258 (2017).

Schennach M, Schneeberger EM, Breuker K. Unfolding and folding of

the three-helix bundle protein KIX in the absence of solvent. J. Am. Soc.

Mass Spectrom. 27, 1079-1088 (2016).

Cabedo Martinez AI, Weinhäupl K, Lee WK, Wolff NA, Storch B, Żerko

S, Konrat R, Koźmiński W, Breuker K, Thévenod F, Coudevylle N. Bio-

chemical and structural characterization of the interaction between

the Siderocalin NGAL/LCN2 and the N-terminal domain of its endocytic

receptor SLC22A17. J. Biol. Chem. 291, 2917-2930 (2016).

Hoernes TP, Clementi N, Faserl K, Glasner H, Breuker K, Lindner H,

Hüttenhofer A, Erlacher M. Nucleotide modifications within bacterial

messenger RNAs regulate their translation and are able to rewire the

genetic code. Nucleic Acids Res. 44, 852-862 (2016).

Flamm AG, Le Roux AL, Mateos B, Díaz-Lobo M, Storch B, Breuker K,

Konrat R, Pons M, Coudevylle N. N-lauroylation during the expression

of recombinant N-myristoylated proteins. Implications and solutions.

Chembiochem. 17, 82-89 (2016).

R. Dallinger

Pedrini-Martha V, Schnegg R, Baurand PE, de Vaufleury A, Dallinger R.

The physiological role and toxicological significance of the non-metal-

selective Cadmium/Copper-Metallothionein isoform differ between

embryonic and adult helicid snails. Comp.Biochem.Physiol. C: Toxicol-

ogy & Pharmacology 199, 38-47 (2017).

Baumann C, Beil A, Jurt S, Niederwanger M, Palacios Ò, Capdevila M,

Atrian S, Dallinger R, Zerbe O. Structural Adaptation of a Protein to

Increased Metal Stress: NMR Structure of a Marine Snail Metallothio-

nein with an Additional Domain. Angew. Chem. Int. Ed. 56, 4617-4622

(2017).

Benito D, Niederwanger M, Izagirre U, Dallinger R, Soto M. Successive

onset of molecular, cellular and tissue-specific responses in midgut gland

of Littorina littorea exposed to sub-lethal cadmium concentrations. Int.

J. Mol. Sci. 18, 1815; doi: 10.3390/ijms18081815, pp. 1-26 (2017).

Niederwanger M, Dvorak M, Schnegg R, Pedrini-Martha V, Bacher K,

Bidoli M, Dallinger R. Challenging the metallothionein (MT) gene of

Biomphalaria glabrata: unexpected response patterns due to cadmium

exposure and temperature stress. Int. J. Mol. Sci. 18, 1747; doi: 10.3390/

ijms18081747, pp. 1-15 (2017).

Niederwanger M, Calatayud S, Zerbe O, Atrian S, Albalat R, Capdevila

M, Palacios Ò, Dallinger R. Biomphalaria glabrata metallothionein:

lacking metal specificity of the protein and missing gene upregulation

suggest metal sequestration by exchangeiInstead of through selective

binding. Int. J. Mol. Sci. 2017, 18, 1457; doi: 10.3390/ijms18071457, pp.

1-15 (2017).

Palacios Ò, Jiménez-Marti E, Niederwanger M, Gil-Moreno S, Zerbe O,

Atrian S, Dallinger R, Capdevila M. Analysis of metal-binding features

of the wild type and two domain-truncated mutant variants of Litto-

rina littorea Metallothionein reveals its Cd-specific character. Int. J. Mol.

Sci. 2017, 18, 1452; doi:10.3390/ijms18071452, pp. 1-16 (2017).

Schmielau L, Dvorak M, Niederwanger M, Dobieszewski N, Pedrini-

Martha V, Ladurner P, Rodríguez-Guerra Pedregal J, Maréchal JD, Dal-

linger R. Differential response to Cadmium exposure by expression of

a two and a three-domain metallothionein isoform in the land winkle

Pomatias elegans: valuating the marine heritage of a land snail. Sci.

Tot. Envion., submitted.

S. Denifl

Huber SE, Smialek MA, Tanzer K, Denifl S. Dissociative electron attach-

ment to the radiosensitizing chemotherapeutic agent hydroxyurea. J.

Chem. Phys. 144, 224309 (2016).

Itälä E, Tanzer K, Granroth S, Kooser K, Denifl S, Kukk E. Fragmentation

patterns of 4(5)-nitroimidazole and 1-methyl-5-nitroimidazole - The

effect of the methylation. J. Mass Spectrom. 52, 770–776 (2017).

Neustetter M, Mahmoodi-Darian M, Denifl S. Study of electron ioniza-

tion and fragmentation of non-hydrated and hydrated tetrahydrofuran

clusters. J. Am. Soc. Mass Spectrom. 28, 866–872 (2017).

Ribar A, Fink K, Li Z, Ptasinska S, Carmichael I, Feketeová L, Denifl S.

Stripping off hydrogens in imidazole triggered by the attachment of a

single electron. Phys. Chem. Chem. Phys. 19, 6406-6415 (2017).

Ribar A, Fink K, Probst M, Huber SE, Feketeová L, Denifl S. Isomer Selec-

tivity in Low-Energy Electron Attachment to Nitroimidazoles. Chemistry

23, 12892-12899 (2017).

Schürmann R, Tanzer K, Dabkowska I, Denifl S, Bald I. Stability of the

Parent Anion of the Potential Radiosensitizer 8-Bromoadenine Formed

by Low-Energy (<3 eV) Electron Attachment. J Phys Chem B: Condensed

Matter, Materials, Surfaces, Interfaces & Biophysical 121, 5730–5734

(2017).

F. Edenhofer

Edenhofer F, Dobeš J, Vobořil M, Brabec T, Dobešová M, Čepková A,

Klein L, Rajewsky K, Filipp D. A novel conditional Aire allele enables

cell-specific ablation of the immune tolerance regulator Aire. Eur. J.

Immunol., Epub ahead of print (2017).

Forero A, Rivero O, Wäldchen S, Ku HP, Kiser DP, Gärtner Y, Penning-

ton LS, Waider J, Gaspar P, Jansch C, Edenhofer F, Resink TJ, Blum R,

Sauer M, Lesch KP. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT

Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain.

Front. Cell. Neurosci. 11, 307 (2017).

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Kwok CK, Ueda Y, Kadari A, Günther K, Heron A, Schnitzler AC, Rook

M, Edenhofer F. Scalable stirred suspension culture for the generation

of billions of human induced pluripotent stem cells using single-use

bioreactors. J. Tiss. Eng. Regen. Med., in press (2017).

Appelt-Menzel A, Cubukova A, Günther K, Edenhofer F, Piontek J,

Krause G, Stüber T, Walles H, Neuhaus W, Metzger M. Establishment

of a Human Blood-Brain Barrier Co-culture Model Mimicking the

Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells.

Stem Cell Reports 8(4), 894-906 (2017).

Wörsdörfer P, Bosen F, Gebhardt M, Russ N, Zimmermann K, Komla

Kessie D, Sekaran T, Egert A, Ergün S, Schorle H, Pfeifer A, Edenhofer

F, Willecke K. Abrogation of Gap Junctional Communication in ES Cells

Results in a Disruption of Primitive Endoderm Formation in Embryoid

Bodies. Stem Cells 35(4), 859-871 (2017).

Wörsdörfer P, Mekala SR, Bauer J, Edenhofer F, Kuerten S, Ergün S.

The vascular adventitia: An endogenous, omnipresent source of stem

cells in the body. Pharmacol. Ther. 171, 13-29 (2016).

Günther K, Menzel AA, Kwok CK, Walles H, Metzger M, Edenhofer F. Rapid

Monolayer Neural Induction of induced Pluripotent Stem Cells Yields Stably

Proliferating Neural Stem Cells. J. Stem Cell Res. Ther. 6, 341(2016).

Safina D, Schlitt F, Romeo R, Pflanzner T, Pietrzik CU, Narayanaswami

V, Edenhofer F, Faissner A. Low-density lipoprotein receptor-related

protein 1 is a novel modulator of radial glia stem cell proliferation,

survival, and differentiation. Glia. 64(8), 1363-80 (2016).

Schulze M, Hoja S, Winner B, Winkler J, Edenhofer F, Riemenschneider

MJ. Model testing of PluriTest® with next-generation sequencing data.

Stem Cells Dev. 25(7), 569-71 (2016).

Münst B, Thier M, Winnemöller D, Helfen M, Thummer RP, Edenhofer

F. Nanog induces suppression of senescence via down-regulation of

p27KIP1 expression. J. Cell. Sci. 129(5), 912-20 (2016).

Scognamiglio R, Cabezas-Wallscheid N, Thier MC, Altamura S, Reyes

A, Prendergast ÁM, Baumgärtner D, Carnevalli LS, Atzberger A, Haas

S, von Paleske L, Boroviak T, Wörsdörfer P, Essers MA, Kloz U, Eisen-

man RN, Edenhofer F, Bertone P, Huber W, van der Hoeven F, Smith

A, Trumpp A. Myc Depletion Induces a Pluripotent Dormant State

Mimicking Diapause. Cell 164(4), 668–680 (2016).

B. Grubeck-Loebenstein

Weinberger B. Vaccines for the elderly: Current use and future chal-

lenges. Immun. Ageing, in press (accepted Dec 1, 2017).

Giacconi R, Costarelli L, Piacenza F, Basso A, Bürkle A, Moreno-Villanueva

M, Grune T, Weber D, Stuetz W, Gonos ES, Schön C, Grubeck-Loebenstein

B, Sikora E, Toussaint O, Debacq-Chainiaux F, Franceschi C, Hervonen

A, Slagboom E, Ciccarone F, Zampieri M, Caiafa P, Jansen E, Dollé MET,

Breusing N, Mocchegiani E, Malavolta M. Zinc-induced metallothionein

in centenarian offspring from a large European population: The MARK-

AGE project. J. Gerontol. A Biol. Sci. Med. Sci., Epub ahead of print (2017).

Weinberger B, Keller M, Putzer C, Breitenberger D, Koller B, Fiegl S,

Moreno-Villanueva M, Bernhardt J, Franceschi C, Voutetakis K, Gonos

ES, Hurme M, Sikora E, Toussaint O, Debacq-Chainiaux F, Grune T,

Breusing N, Bürkle A, Grubeck-Loebenstein B. Protection against Teta-

nus and Diphtheria in Europe: The impact of age, gender and country

of origin based on data from the MARK-AGE Study. Exp. Gerontol.,

pii: S0531-5565(17)30516-8 (2017).

Weinberger B, Keller M, Grubeck-Loebenstein B. Long-term mainte-

nance of diphtheria-specific antibodies after booster vaccination is

hampered by latent infection with Cytomegalovirus. Immun. Ageing

14, 16 (2017).

Pangrazzi L, Naismith E, Meryk A, Keller M, Jenewein B, Trieb K,

Grubeck-Loebenstein B. Increased IL-15 production and accumulation

of highly differentiated CD8+ effector/memory T cells in the bone mar-

row of persons with Cytomegalovirus. Front. Immunol. 8, 715 (2017).

Pangrazzi L, Meryk A, Naismith E, Koziel R, Lair J, Krismer M, Trieb K,

Grubeck-Loebenstein B. “Inflamm-aging” influences immune cell sur-

vival factors in human bone marrow. Eur. J. Immunol. 47, 481-492 (2017).

Weinberger B. Immunosenescence: The importance of considering age

in health and disease. Clin. Exp. Immunol. 187, 1-3 (2017).

Weinberger B. Adult vaccination against tetanus and diphtheria: The

European perspective. Clin. Exp. Immunol. 187, 93-99 (2017).

Stuetz W, Weber D, Dollé MET, Jansen E, Grubeck-Loebenstein B, Fiegl

S, Toussaint O, Bernhardt J, Gonos ES, Franceschi C, Sikora E, Moreno-

Villanueva M, Breusing N, Grune T, Bürkle A. Plasma carotenoids,

tocopherols, and retinol in the age-stratified (35-74 years) general

population: Cross-sectional study in six European countries. Nutrients

8, 614 (2016).

Zlamy M, Almanzar G, Parson W, Schmidt C, Leierer J, Weinberger B,

Jeller V, Unsinn K, Eyrich M, Würzner R, Prelog M. Efforts of the hu-

man immune system to maintain the peripheral CD8+ T cell compart-

ment after childhood thymectomy. Immunity & Ageing 13, 3 (2016).

Pinti M, Appay V, Campisi J, Frasca D, Fülöp T, Sauce D, Larbi A,

Weinberger B, Cossarizza A. Aging of the immune system: Focus on

inflammation and vaccination. Eur. J. Immunol. 46, 2286-2301 (2016).

Grasse M, Meryk A, Schirmer M, Grubeck-Loebenstein B, Weinberger

B. Booster vaccination against tetanus and diphtheria: Insufficient

protection against diphtheria in young and elderly adults. Immun.

Ageing 13, 26 (2016).

Ciccarone F, Malavolta M, Calabrese R, Guastafierro T, Bacalini MG,

Reale A, Franceschi C, Capri M, Hervonen A, Hurme M, Grubeck-

Loebenstein B, Koller B, Bernhardt J, Schön C, Slagboom PE, Toussaint

O, Sikora E, Gonos ES, Breusing N, Grune T, Jansen E, Dollé M,

Moreno-Villanueva M, Sindlinger T, Bürkle A, Zampieri M, Caiafa P.

Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a

large European population enrolled in the MARK-AGE study. Aging

Cell 15, 755-765 (2016).

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Weinberger B, Joos C, Reed SG, Coler R, Grubeck-Loebenstein B. The

stimulatory effect of the TLR4-mediated adjuvant glucopyranosyl lipid

A is well preserved in old age. Biogerontology 17, 177-187 (2016).

Grubeck-Loebenstein B, Pangrazzi L. Role of the bone marrow for

adaptive immunity in old age. In: Handbook of Immunosenescence, 2nd

edition, Fulop T, Franceschi C, Hirokawa K, Pawelec G (eds), Springer,

in press

Weinberger B. Effects of ageing on the vaccination response. In: The

Ageing Immune System and Health. Bueno V, Lord J, Jackson T (eds),

Springer International Publishing Switzerland 2017, pp 69-86. ISBN 978-

3-319-43365-3

R. Gust

Kaserer T, Obermoser V, Weninger A, Gust R, Schuster D. Evaluation

of selected 3D virtual screening tools for the prospective identification

of peroxisome proliferator-activated receptor (PPAR)γ partial agonists.

European Journal of Medicinal Chemistry 124, 49-62 (2016).

Obermoser V, Urban ME, Murgueitio MS, Wolber G, Gust R. New

telmisartan-derived PPAR γ agonists: impact of the 3D-binding mode

on the pharmacological profile. European Journal of Medicinal

Chemistry 124, 138-152 (2016).

Kinthada P, Gust R. Synthesis and characterization, nuclease activity

studies and anticancer activity of Au(III)isostatinthiosemicarbazone

complexes as potential anticancer drugs. World Journal of Pharmacy

and Pharmaceutical Science 8, 727-739 (2016).

Liu W, Gust R. Update on metal N-heterocyclic carbene complexes as

potential anti-tumor metallodrugs. Coordination Chemical Reviews

329, 191-213 (2016).

Obermoser V, Mauersberger R, Schuster D, Czifersky M, Lipova M,

Siegl M, Kintscher U, Gust R. Importance of 5/6-aryl substitution on

the pharmacological profile of 4´-((2-propyl-1H-benzo[d]imidazol-1-yl)

methyl)-[1,1´-biphenyl]-2-carboxylic acid derived PPARγ agonists.

European Journal of Medicinal Chemistry 126, 590-603 (2017).

Maia P I da S, Carneiro Z A, Lopes C D, Oliveira C G, Silva J S, de Albu-

querque S, Hagenbach A, Gust R, Deflon V M, Abram U. Organometal-

lic gold(III) complexes with hybrid SNS-donating thiosemicarbazone

ligands: cytotoxicity and anti-trypanosoma cruzi activity. Dalton

Transaction 46, 2559-2571 (2017).

B. Hobmayer, P. Ladurner

Wudarski J, Simanov D, de Mulder K, Ustyantsev K, Grelling M, Grud-

niewska M, Beltman F, Glazenburg L, Demircan T, Wunderer J, Qi W,

Vizoso DB, Weissert PM, Olivieri D, Mouton S, Guryev V, Aboobaker A,

Scharer L, Ladurner P, Berezikov E. Efficient transgenesis and annotated

genome sequence of the regenerative flatworm model Macrostomum

lignano. Nature Comm. 8, 2120 (2017).

Lengerer B, Wunderer J, Pjeta R, Carta G, Kao D, Aboobaker A, Beisel

C, Berezikov E, Salvenmoser W, Ladurner P. Organ specific gene expres-

sion in the regenerating tail of Macrostomum lignano. Dev. Biol. 433,

448-460 (2017).

Demeuldre M, Hennebert E, Bonneel M, Lengerer B, Van Dyck S, Wat-

tiez R, Ladurner P, Flammang P. Mechanical adaptability of sea cucum-

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Aufschnaiter R, Wedlich-Söldner R, Zhang X, Hobmayer B. Apical and

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tion. Biol. Open 6, 1137-1148 (2017).

Dobner J, Ress C, Rufinatscha K, Salzmann K, Salvenmoser W, Folie

S, Wieser V, Moser P, Weiss G, Goebel G, Tilg H, Kaser S. Fat-enriched

rather than high-fructose diets promote whitening of adipose tissue in

a sex-dependent manner. J. Nutrit. Biochem. 49, 22-29 (2017).

Egger B, Bachmann L, Fromm B. Atp8 is in the ground pattern of flat-

worm mitochondrial genomes. BMC Genomics 18, 414 (2017).

Farkas J, Salaberria I, Styrishave B, Staňková R, Ciesielski TM, Olsen AJ,

Posch W, Flaten TP, Krøkje Å, Salvenmoser W, Jenssen BM. Exposure

of juvenile turbot (Scophthalmus maximus) to silver nanoparticles and

17α-ethinylestradiol mixtures: Implications for contaminant uptake and

plasma steroid hormone levels. Envir. Pollution A 220, 328-336 (2017).

Gammoudi M, Garbouj M, Egger B, Tekaya S. Updated inventory and

distribution of free-living flatworms from Tunisian waters. Zootaxa

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Krasnokutski SA, Goulart M, Gordon EB, Ritsch A, Jäger C, Rastogi M,

Salvenmoser W, Henning T, Scheier P. Low-temperature condensation

of carbon. Astrophys. J. 847, 89 (2017).

Robertson HE, Lapraz F, Egger B, Telford MJ, Schiffer PH. The mito-

chondrial genomes of the acoelomorph worms Paratomella rubra,

Isodiametra pulchra and Archaphanostoma ylvae. Scientific Reports 7,

1847 (2017).

Rodrigues M, Ostermann T, Kremeser L, Lindner H, Beisel C, Berezikov

E, Hobmayer B, Ladurner P. Profiling of adhesive-related genes in the

freshwater cnidarian Hydra magnipapillata by transcriptomics and

proteomics. Biofouling 32, 1115-1129 (2016).

Lengerer B, Flammang P, Salvenmoser W, Ladurner P. Adhesive Organ

regeneration in Macrostomum lignano. BMC Dev. Biol. 16, 20 (2016).

Plusquin M, De Mulder K, Van Belleghem F, DeGheselle O, Pirotte N,

Willems M, Cuypers A, Salvenmoser W, Ladurner P, Artois T, Smeets

K. Toxic effects of cadmium on flatworm stem cell dynamics: A tran-

scriptomic and ultrastructural elucidation of underlying mechanisms.

Environ. Toxicol. 31, 1217-1228 (2016).

Rivera-Ingraham GA, Nommick A, Blondeau-Bidet E, Ladurner P, Lignot

JH. Salinity stress from the perspective of the energy-redox axis: Lessons

from a marine intertidal flatworm. Redox Biol. 10, 53-64 (2016).

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mayer B, Ladurner P. The cellular basis of bioadhesion of the freshwater

polyp Hydra. BMC Zoology 1, 3 (2016).

Seybold A, Salvenmoser W, Hobmayer B. Sequential development of

apical-basal and planar polarity in aggregating epitheliomuscular cells

in Hydra. Dev. Biol. 412, 148-159 (2016).

Gammoudi M, Salvenmoser W, Harrath AH, Tekaya S, Egger B. Ultra-

structure of spermatogenesis and mature spermatozoa in the flatworm

Prosthiostomum siphunculus (Polycladida, Cotylea). Cell Biol. Internat.

40, 277-288 (2016).

Gammoudi M, Salvenmoser W, Tekaya S, Egger B. Ultrastructure of

the ovary and oogenesis in the flatworm Prosthiostomum siphunculus

(Polycladida, Cotylea). Cell Biol. Internat. 40, 1174-1186 (2016).

Kari W, Zeng F, Zitzelsberger L, Will JP, Rothbächer U. Embryo micro-

injection and electroporation in the chordate Ciona intestinalis. JOVE

116, e54313 (2016).

Ott E, Wendik B, Srivastava M, Pacho F, Töchterle S, Salvenmoser W,

Meyer D. Pronephric tubule morphogenesis in zebrafish depends on

Mnx mediated repression of irx1b within the intermediate mesoderm.

Dev. Biol. 411, 101-114 (2016).

Zobl S, Salvenmoser W, Schwerte T, Gebeshuber I, Schreiner M. Morpho

peleides butterfly wing imprints as structural colour stamp. Bioinsp.

Biomim. 11, 016006 (2016).

Oda-Ishii I, Kubo A, Kari W, Suzuki N, Rothbächer U, Satou Y. A ma-

ternal system initiating the zygotic developmental program through

combinatorial repression in the ascidian embryo. PLoS Genetics 12,

e1006045 (2016).

Egger B. Making heads or tails of tapeworms. Trends Parasit. 32, 511-

512 (2016).

Juliano C, Hobmayer B. Animal evolution: New perspectives from early

emerging metazoans. BioEssays 38, 216-219 (2016).

P. Jansen-Dürr

Meitzler JL, Makhlouf HR, Antony S, Wu Y, Butcher D, Jiang G, Juhasz A,

Lu J, Dahan I, Jansen-Dürr P, Pircher H, Shah AM, Roy K, Doroshow JH.

Decoding NADPH oxidase 4 expression in human tumors. Redox Biol.

13, 182-195 (2017).

Kofler B, Borena W, Manzl C, Dudas J, Wegscheider AS, Jansen-Dürr P,

Schartinger V, Riechelmann H. Sensitivity of tumor surface brushings

to detect human papilloma virus DNA in head and neck cancer. Oral

Oncol. 67,103-108 (2017).

Agorastos T, Chatzistamatiou K, Moysiadis T, Kaufmann AM, Skenderi

A, Lekka I, Koch I, Soutschek E, Boecher O, Kilintzis V, Angelidou S,

Katsiki E, Hagemann I, Boschetti Gruetzmacher E, Tsertanidou A, Ange-

lis L, Maglaveras N, Jansen-Duerr P. Human papillomavirus E7 protein

detection as a method of triage to colposcopy of HPV positive women,

in comparison to genotyping and cytology. Final results of the PIPAVIR

study. Int. J. Cancer 141(3), 519-530 (2017).

Chatzistamatiou K, Moysiadis T, Angelis E, Kaufmann A, Skenderi A,

Jansen-Duerr P, Lekka I, Kilintzis V, Angelidou S, Katsiki E, Hagemann I,

Tsertanidou A, Koch I, Boecher O, Soutschek E, Maglaveras N, Agoras-

tos T. Diagnostic accuracy of high-risk HPV DNA genotyping for primary

cervical cancer screening and triage of HPV-positive women, compared

to cytology: preliminary results of the PIPAVIR study. Arch. Gynecol.

Obstet. 295(5),1247-1257 (2017).

Petit M, Koziel R, Etemad S, Pircher H, Jansen-Dürr P. Depletion of

oxaloacetate decarboxylase FAHD1 inhibits mitochondrial electron

transport and induces cellular senescence in human endothelial cells.

Exp. Gerontol. 92, 7-12 (2017).

Khan A, Dellago H, Terlecki-Zaniewicz L, Karbiener M, Weilner S,

Hildner F, Steininger V, Gabriel C, Mück C, Jansen-Dürr P, Hacobian A,

Scheideler M, Grillari-Voglauer R, Schosserer M, Grillari J. SNEVhPrp19/

hPso4 Regulates Adipogenesis of Human Adipose Stromal Cells. Stem

Cell Reports 8(1), 21-29 (2017).

Weilner S, Schraml E, Wieser M, Messner P, Schneider K, Wassermann

K, Micutkova L, Fortschegger K, Maier AB, Westendorp R, Resch H,

Wolbank S, Redl H, Jansen-Durr P, Pietschmann P, Grillari-Voglauer R,

and Grillari J. Secreted microvesicular miR-31 inhibits osteogenic differ-

entiation of mesenchymal stem cells. Aging Cell 15 (4), 744-54 (2016).

Weiher H, Pircher H, Jansen-Durr P, Hegenbarth S, Knolle P, Grunau S,

Vapola M, Hiltunen JK, Zwacka RM, Schmelzer E, Reumann K, and Will

H. A monoclonal antibody raised against bacterially expressed MPV17

sequences shows peroxisomal, endosomal and lysosomal localisation in

U2OS cells. BMC Res. Notes 9, 128 (2016).

Prior KK, Wittig I, Leisegang MS, Groenendyk J, Weissmann N, Michalak

M, Jansen-Durr P, Shah AM, and Brandes RP. The Endoplasmic Reticu-

lum Chaperone Calnexin Is a NADPH Oxidase NOX4 Interacting Protein.

J. Biol. Chem. 291(13), 7045-59 (2016).

Nlandu-Khodo S, Dissard R, Hasler U, Schafer M, Pircher H, Jansen-Durr

P, Krause KH, Martin PY, and de Seigneux S. NADPH oxidase 4 deficiency

increases tubular cell death during acute ischemic reperfusion injury.

Sci. Rep. 6, 38598 (2016).

Holl M, Koziel R, Schafer G, Pircher H, Pauck A, Hermann M, Klocker

H, Jansen-Durr P, and Sampson N. ROS signaling by NADPH oxidase 5

modulates the proliferation and survival of prostate carcinoma cells.

Mol. Carcinog. 55 (1), 27-39 (2016).


Cavinato M, Koziel R, Romani N, Weinmullner R, Jenewein B, Hermann

M, Dubrac S, Ratzinger G, Grillari J, Schmuth M, and Jansen-Durr P.

UVB-Induced Senescence of Human Dermal Fibroblasts Involves Impair-

ment of Proteasome and Enhanced Autophagic Activity. J. Gerontol. A

Biol. Sci. Med. Sci. 72 (5), 632-639 (2016).

Bu H, Baraldo G, Lepperdinger G, and Jansen-Durr P. mir-24 activity

propagates stress-induced senescence by down regulating DNA topoi-

somerase 1. Exp. Gerontol. 75, 48-52 (2016).

Cavinato M, Waltenberger B, Baraldo G, Grade CVC, Stuppner H,

Jansen-Dürr P. Plant extracts and natural compounds used against UVB-

induced photoaging. Biogerontology 18(4), 499-516 (2017).

Bu H, Wedel S, Cavinato M, Jansen-Dürr P. MicroRNA Regulation of

Oxidative Stress-Induced Cellular Senescence. Oxid. Med. Cell. Longev.

2017:2398696 (2017).

Egea J, Fabregat I, Frapart YM, Ghezzi P, Görlach A, Jansen-Dürr P,

Daiber A. European contribution to the study of ROS: A summary of

the findings and prospects for the future from the COST action BM1203

(EU-ROS). Redox Biol. 13, 94-162 (2017).

Cavinato M, Jansen-Dürr P. Molecular mechanisms of UVB-induced

senescence of dermal fibroblasts and its relevance for photoaging of

the human skin. Exp. Gerontol. 94, 78-82 (2017).

Erusalimsky JD, Grillari J, Grune T, Jansen-Duerr P, Lippi G, Sinclair AJ,

Tegnér J, Viña J, Durrance-Bagale A, Miñambres R, Viegas M, Rodríguez-

Mañas L. FRAILOMIC Consortium. In Search of ‘Omics’-Based Biomark-

ers to Predict Risk of Frailty and Its Consequences in Older Individuals:

The FRAILOMIC Initiative. Gerontology 62(2), 182-90 (2016).

Lippi G, Jansen-Duerr P, Viña J, Durrance-Bagale A, Abugessaisa I, Go-

mez-Cabrero D, Tegnér J, Grillari J, Erusalimsky J, Sinclair A, Rodriguez-

Manãs L. FRAILOMIC consortium.Laboratory biomarkers and frailty:

presentation of the FRAILOMIC initiative. Clin. Chem. Lab. Med. 53(10),

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I. Kranner

Karadar M, Neuner G, Kranner I, Holzinger A, Buchner O. Solar irra-

diation levels during simulated long and short-term heat waves sig-

nificantly influence heat survival, pigment and ascorbate composition,

and free radical scavenging activity in alpine Vaccinium gaultherioides.

Physiol. Plantarum doi: 10.1111/ppl.12686 (2017).

Fernández-Marín B, Míguez F, Méndez-Fernández L, Agut A, Becer-

ril JM, García-Plazaola JI, Kranner I, Colville L. Seed carotenoid and

tocochromanol composition of wild Fabaceae species is shaped by

phylogeny and ecological factors. Front. Plant Sci. 8, 1428 (2017).

Calvi GP, Anjos AMG, Kranner I, Pritchard HW, Ferraz IDK. Exceptional

flooding tolerance in the totipotent recalcitrant seeds of Eugenia stipi-

tata. Seed Sci. Res. 27, 121-130 (2017).

Ganthaler A, Stöggl W, Mayr S, Kranner I, Schüler S, Wischnitzki E, Sehr

EM, Fluch S, Trujillo-Moya C. Association genetics of phenolic needle

compounds in Norway spruce with variable susceptibility to needle

bladder rust. Plant Mol. Biol. 94, 229-251 (2017).

Aigner S, Holzinger A, Karsten U, Kranner I. The freshwater red alga

Batrachospermum turfosum (Florideophyceae) can acclimate to a wide

range of light and temperature conditions. Eur. J. Phycol. 52, 238-249

(2017).

Gerna D, Roach T, Stöggl W, Wagner J, Vaccino P, Limonta M, Kranner

I. Changes in low-molecular-weight thiol-disulphide redox couples are

part of bread wheat seed germination and early seedling growth. Free

Radical Res. 51, 568-581 (2017).

Calvi GP, Aud FF, Ferraz IDK, Pritchard HW, Kranner I. Analyses of several

seed viability markers in individual recalcitrant seeds of Eugenia stipi-

tata McVaugh with totipotent germination. Plant Biol. 19, 6-13 (2017).

Buchner O, Roach T, Gertzen J, Schenk S, Karadar M, Stöggl W, Miller

R, Bertel C, Neuner G, Kranner I. Drought affects the heat-hardening

capacity of alpine plants as indicated by changes in xanthophyll cycle

pigments, singlet oxygen scavenging, α-tocopherol and plant hor-

mones. Environ. Exp. Bot. 133, 159-175 (2017).

García-Plazaola JI, Portillo-Estrada M, Fernández-Marín B, Kannaste

A, Niinemets U. Emissions of carotenoid cleavage products upon heat

shock and mechanical wounding from a foliose lichen. Environ. Exp.

Bot. 133, 87-97 (2017).

Roach T, Baur T, Stöggl W, Krieger-Liszkay A. Chlamydomonas re-

inhardtii responding to high light: a role for 2-propenal (acrolein).

Physiol. Plant. 161, 75-87 (2017).

Roach T, Na CS. LHCSR3 affects de-coupling and re-coupling of LHCII to

PSII during state transitions in Chlamydomonas reinhardtii. Sci. Rep. 7,

43145 (2017).

Galland M, He D, Lounifi I, Arc E, Clement G, Balzergue S, Huguet S,

Cueff G, Godin B, Collet B, Granier F, Morin H, Tran J, Valot B, Rajjou L.

An integrated “Multi-Omics” Comparison of embryo and endosperm

tissue-specific features and their impact on rice seed quality. Front.

Plant Sci. 8, 1984 (2017).

García-Plazaola JI, Fernández-Marín B, Ferrio JP, Alday JG, Hoch G,

Landais D, Milcu A, Tissue DT, Voltas J, Gessler A, Roy J, de Dios VR.

Endogenous circadian rhythms in pigment composition induce changes

in photochemical efficiency in plant canopies. Plant Cell Environ. 40,

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Míguez F, Fernández-Marín B, Becerril JM, García-Plazaola JI. Diver-

sity of winter photoinhibitory responses: a case study in co-occurring

lichens, mosses, herbs and woody plants from subalpine environments.

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Candotto Carniel F, Gerdol M, Montagner A, Banchi E, De Moro G,

Manfrin C, Muggia L, Pallavicini A, Tretiach M. New features of desicca-

tion tolerance in the lichen photobiont Trebouxia gelatinosa revealed

by a transcriptomic approach. Plant Mol. Biol. 91, 319-339 (2016).

Eckert EM, Di Cesare A, Stenzel B, Fontaneto D, Corno G. Daphnia as a

refuge for an antibiotic resistance gene in an experimental freshwater

community. Sci. Total Environ. 571, 77-81 (2016).

Peguero-Pina JJ, Sisó S, Fernández-Marín B, Flexas J, Galmés J,

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functional plasticity decreases the water consumption without further

consequences for carbon uptake in Quercus coccifera L. under Mediter-

ranean conditions. Tree Physiol. 36, 356-367 (2016).

B. Kräutler, T. Müller

Kräutler B. Breakdown of Chlorophyll in Higher Plants - Phyllobilins as

Abundant, Yet Hardly Visible Signs of Ripening, Senescence and Cell

Death (Review). Angew. Chem. Int. Ed. 55, 4882-4907 (2016).

Der Chlorophyll-Abbau in höheren Pflanzen – Phyllobiline als weit-

verbreitete, aber kaum sichtbare Zeichen von Reifung, Seneszenz und

Zelltod. Angew. Chem. 128, 4964-4990 (2016).

Netsomboon K, Feßler A, Erletz L, Prüfert F, Ruetz M, Kieninger C,

Kräutler B, Bernkop-Schnürch A. Vitamin B12 and derivatives-in vitro

permeation studies across Caco-2 cell monolayers and freshly excised

rat intestinal mucosa. Int. J. Pharm. 497, 129-135 (2016).

Li C, Kräutler B. Zn-complex of a natural yellow chlorophyll catabolite.

J. Porph. Phthalocyanines 20, 388-396 (2016).K Gruber, Kräutler B.

Coenzyme B12 Repurposed for Photo-regulation of Gene Expression.

Angew. Chem. Int. Ed. 55, 5638-5640 (2016).

Coenzym B12 – Umfunktioniert für die Photo-Regulation der Genex-

pression. Angew. Chem. 128, 5728-5730 (2016).

Helliwell KE, Lawrence AD, Holzer A, Kudahl UJ, Sasso S, Kräutler B,

Scanlan DJ, Warren MJ, Smith AG. Cyanobacteria and eukaryotic algae

use different chemical variants of vitamin B12. Current Biol. 26, 999-1008

(2016).

Li C, Wurst K, Feng Y, Kräutler B. Synthesis, spectroscopic and crystal-

lographic analysis of the Zn-complex of a di-(β,β”-sulfoleno) pyrin

– Model for Zn-complexes of bilirubin and of phylloxanthobilins.

Monatsh. Chem. 147, 1031-1036 (2016).

Banala S, Wurst K, Kräutler B. Panchromatic π-Extended Porphyrins

from Conjugation with Quinones. ChemPlusChem. 81, 477-488 (2016).

Scherl M, Müller T, Kreutz CR, Huber RG, Zass E, Liedl KR, Kräutler B.

Chlorophyll Catabolites in Fall Leaves of the Wych Elm Tree Present a

Novel Glycosylation Motif.Chem. Eur. J. 22, 9498-9503 (2016).

Widner FJ, Lawrence AD, Deery E, Heldt D, Frank S, Gruber K, Wurst K,

Warren MJ, Kräutler B.Total Synthesis, Structure and Biological Activity

of Adenosylrhodibalamin – the Nonnatural Rhodium Homologue of

Coenzyme B12. Angew. Chem. Int. Ed. 55, 11281-11289 (2016).

Totalsynthese, Struktur und biologische Aktivität von Adenosylrhod-

ibalamin, dem nichtnatürlichen Rhodiumhomologen von Coenzym B12.

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Erhart T, Mittelberger C, Vergeiner C, Scherzer G, Holzner B, Robatscher

P, Oberhuber M, Kräutler B.Chlorophyll Catabolites in Senescent Leaves

of the Plum Tree (Prunus domestica). Chem. & Biodiversity 13, 1441-

1453 (2016).

Guzzo MB, Nguyen HT, Pham TH, Wyszczelska-Rokiel M, Jakubowski

H, Wolff KA, Ogwang S, Timpona JL, Gogula S, Jacobs MR, Ruetz M,

Kräutler B, Jacobsen DW, Zhang GF, Nguyen L. Methylfolate Trap Pro-

motes Bacterial Thymineless Death by Sulfa Drugs. PLOS Pathogens 12,

e1005949, (2016).

C Li, K Wurst, S Jockusch, K Gruber, M Podewitz, KR Liedl, B.Kräutler.

Chlorophyll-Derived Yellow Phyllobilins of Higher Plants are Medium-

Responsive, Chiral Photoswitches. Angew. Chem. Int. Ed. 55, 15760-

15765, (2016).

Von Chlorophyll abstammende gelbe Phyllobiline höherer Pflanzen

als umgebungsgesteuerte, chirale Photoschalter. Angew. Chem. 128,

15992-15997 (2016).

Miller NA, Wiley TE, Spears KG, Ruetz M, Kieninger C, Kräutler B,

Sension RJ. Toward the Design of Photoresponsive Conditional Antivi-

tamins B12: A Transient Absorption Study of an Arylcobalamin and an

Alkynylcobalamin. J. Am. Chem. Soc. 138, 14250-14256 (2016).

Mireku SA, Ruetz MM, Zhou T, Korkhov VM, Kräutler B, Locher

KP.Conformational Change of a Tryptophane Residue in BtuF Facilitätes

Binding and Transport of Cobinamide by the Bacterial Vitamin B12

Transporter BtuCD-F. Scient Reports 7, 41575 (2017).

Mittelberger C, Yalcinkaya H, Pichler C, Gasser J, Scherzer G, Erhart T,

Schumacher S, Holzner B, Janik K, Robatscher P, Müller T, Kräutler B,

Oberhuber M. Pathogen-Induced Leaf Chlorosis: Products of Chloro-

phyllBreakdown Found in Degreened Leaves of Phytoplasma-Infect-

edApple (Malus × domestica Borkh.) and Apricot (Prunus armeniaca L.)

Trees Relate to the Pheophorbide a Oxygenase/Phyllobilin Pathway. J.

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Ruetz M, Shanmuganathan A, Gherasim C, Karasik A, Salchner R,

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B12 Inhibition of Human B12-Processing Enzyme CblC - Crystal Structure

of Abortive Ternary Complex with Cosubstrate Glutathione. Angew.

Chem. Int. Ed. 56, 7387-7392 (2017).

Inhibierung des humanen B12-verarbeitenden Enzyms CblC durch An-

tivitamine B12 – Kristallstruktur des inaktiven ternären Komplexes mit

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Li Z, Shanmuganathan A, Ruetz M, Yamada K, Lesniak NA, Kräutler

B, Brunold TC, Koutmos M Banerjee R. Glutathionyl-Cobalamin is an

Intermediate in Thiol Oxidation Catalyzed by the B12 Trafficking Protein

CblC. J. Biol. Chem. 292, 9733-974 (2017).

Brenig CN, Ruetz M, Kieninger C, Wurst K, Kräutler B. Alpha- and

beta-Diastereoisomers of Phenylcobalamin from Cobalt-Arylation with

Diphenyliodonium Chloride. Chemistry – Europ. J. 23, 9726-9731 (2017).

Banala S, Fokong S, Brand Ch, Andreou Ch, Kräutler B, Rueping M,

Kiessling F. Quinone-Fused Porphyrins as Contrast Agents for Photoa-

coustic Imaging. Chem. Sci. 8, 6176-6181 (2017).

Widner FJ, Gstrein F, Kräutler B. Partial Synthesis of Coenzyme B12 from

Cobyric Acid. Helv. Chim. Acta 100, e1700170 (2017).

Bloch JS, Ruetz M, Kräutler B, Locher KP.Structure of the human trans-

cobalamin beta domain in four distinct states. PloS One 12(9): e0184932

(2017).

Mutti E, Hunger M, Fedosov S, Nexo E, Kräutler B. Organometallic

DNA-B12-Conjugates as Potential Oligonucleotide Vectors - Synthesis,

Structural and Binding Studies with Human Cobalamin-Transport Pro-

teins. Chembiochem. 18, 2280-2291 (2017).

Moser S, Scherzer G, Kräutler B. On the Nature of Isomeric Nonfluores-

cent Chlorophyll Catabolites in Leaves and Fruit - A Study with a Ubiq-

uitous Phylloleucobilin and its Main Isomerization Product. Chemistry

and Biodiversity 14, e1700368 (2017).

Kuprian E, Munkler C, Resnyak A, Zimmermann S, Tuong TD, Gierlinger

N, Müller T, Livingston III DP, Neuner G. Complex bud architecture and

cell-specific chemical patterns enable supercooling of Picea abies bud

primordia. Plant Cell Environ. 40, 3101–3112 (2017).

K. Liedl, D. Schuster

Vuorinen A, Engeli RT, Leugger S, Kreutz CR, Schuster D, Odermatt

A, Matuszczak B. Phenylbenzenesulfonates and-sulfonamides as

17β-hydroxysteroid dehydrogenase type 2 inhibitors: Synthesis and

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Vuorinen A, Engeli RT, Leugger S, Bachmann F, Akram M, Atanasov AG,

Waltenberger B, Temml V, Stuppner H, Krenn L. Potential Antiosteopo-

rotic Natural Product Lead Compounds That Inhibit 17β-Hydroxysteroid

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Vitzthum D, Schauperl M, Liedl KR, Huppertz H. High-pressure synthesis

and crystal structure of In3B5O12. Zeitschrift für Naturforschung B

72(1), 69-76 (2017).

Temml V, Garscha U, Romp E, Schubert G, Gerstmeier J, Kutil Z, Ma-

tuszczak B, Waltenberger B, Stuppner H, Werz O. Discovery of the first

dual inhibitor of the 5-lipoxygenase-activating protein and soluble

epoxide hydrolase using pharmacophore-based virtual screening. Sci.

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Stemeseder T, Freier R, Wildner S, Fuchs JE, Briza P, Lang R, Batanero

E, Lidholm J, Liedl KR, Campo P. Crystal structure of Pla l 1 reveals both

structural similarity and allergenic divergence within the Ole e 1–like

protein family. J. Allergy Cli. Immunol. 140(1), 277-80 (2017).

Schmitt MK, Podewitz M, Liedl KR, Huppertz H. High-Pressure Synthesis

and Characterization of the Ammonium Yttrium Borate (NH4) YB8O14.

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Schauperl M, Podewitz M, Ortner TS, Waibl F, Thoeny A, Loerting T, Liedl

KR. Balance between hydration enthalpy and entropy is important for

ice binding surfaces in Antifreeze Proteins. Sci. Rep. 7(1), 11901 (2017).

Schauperl M, Czodrowski P, Fuchs JE, Huber RG, Waldner BJ, Podewitz

M, Kramer C, Liedl KR. Binding Pose Flip Explained via Enthalpic and

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Rossi D, Rui M, Di Giacomo M, Schepmann D, Wuensch B, Monteleone

S, Liedl KR, Collina S. Gaining in pan-affinity towards sigma 1 and sigma

2 receptors. SAR studies on arylalkylamines. Bioorg. Med. Chem. 25(1),

11-9 (2017).

Peduto A, Scuotto M, Krauth V, Roviezzo F, Rossi A, Temml V, Esposito V,

Stuppner H, Schuster D, D’Agostino B. Optimization of benzoquinone

and hydroquinone derivatives as potent inhibitors of human 5-lipoxy-

genase. Eur. J. Med. Chem. 127, 715-26 (2017).

Obermoser V, Mauersberger R, Schuster D, Czifersky M, Lipova M,

Siegl M, Kintscher U, Gust R. Importance of 5/6-aryl substitution on the

pharmacological profile of 4ʹ-((2-propyl-1H-benzo [d] imidazol-1-yl)

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Monteleone S, Lieb A, Pinggera A, Negro G, Fuchs JE, Hofer F, Striessnig

J, Tuluc P, Liedl KR. Mechanisms Responsible for ω-Pore Currents in Ca v

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Monteleone S, Fuchs JE, Liedl KR. Molecular Connectivity Predefines

Polypharmacology: Aliphatic Rings, Chirality, and sp3 Centers Enhance

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Hoffmann A, Richter M, von Grafenstein S, Walther E, Xu Z, Schumann

L, Grienke U, Mair CE, Kramer C, Rollinger JM. Discovery and Character-

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Neuraminidases. Front. Microbiol. 8, 205 (2017).

Hochleitner J, Akram M, Ueberall M, Davis RA, Waltenberger B,

Stuppner H, Sturm S, Ueberall F, Gostner JM, Schuster D. A combinato-

rial approach for the discovery of cytochrome P450 2D6 inhibitors from

nature. Sci. Rep. 7(1), 8071 (2017).

Hitzenberger M, Schuster D, Hofer TS. The Binding Mode of the Sonic

Hedgehog Inhibitor Robotnikinin, a combined Docking and QM/MM

MD Study. Front. Chem. 5, 76 (2017).

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| Hanáková Z, Hošek J, Kutil Zf, Temml V, Landa Pe, Vanek Ts, Schuster

D, Dall’Acqua S, Cvacka J, Polansky Oe. Anti-inflammatory Activity of

Natural Geranylated Flavonoids: Cyclooxygenase and Lipoxygenase

Inhibitory Properties and Proteomic Analysis. J. Nat. Prod. 80(4), 999-

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Conformational Flexibility Differentiates Naturally Occurring Bet v 1

Isoforms. Int. J. Mol. Sci. 18(6), 1192 (2017).

Garscha U, Romp E, Pace S, Rossi A, Temml V, Schuster D, König S, Gerst-

meier J, Liening S, Werner M. Pharmacological profile and efficiency in

vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating

protein and soluble epoxide hydrolase. Sci. Rep. 7(1), 9398 (2017).

Engeli RT, Rohrer SR, Vuorinen A, Herdlinger S, Kaserer T, Leugger S,

Schuster D, Odermatt A. Interference of Paraben Compounds with

Estrogen Metabolism by Inhibition of 17β-Hydroxysteroid Dehydroge-

nases. Int. J. Mol. Sci. 18(9), 2007 (2017).

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ficity from Proteomics-De rived Peptide Substrate Data. Curr. Protein.

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Dreier D, Latkolik S, Rycek L, Schnürch M, Dymáková A, Atanasov AG,

Ladurner A, Heiss EH, Stuppner H, Schuster D. Linked magnolol dimer

as a selective PPARγ agonist–Structure-based rational design, synthesis,

and bioactivity evaluation. Sci. Rep. 7(1), 13002 (2017).

Bruns J, Podewitz M, Schauperl M, Joachim B, Liedl KR, Huppertz H.

CaB2S4O16: A Borosulfate Exhibiting a New Structure Type with Phyl-

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Bernard J, Köck E-M, Huber RG, Liedl KR, Call L, Schlögl R, Grothe H,

Loerting T. Carbonic acid monoethyl ester as a pure solid and its confor-

mational isomerism in the gas-phase. Rsc Adv. 7(36), 22222-33 (2017).

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cations in short-chain dehydrogenase/reductase research. J. Steroid

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Beck KR, Bächler M, Vuorinen A, Wagner S, Akram M, Griesser

U, Temml V, Klusonova P, Yamaguchi H, Schuster D. Inhibition of

11β-hydroxysteroid dehydrogenase 2 by the fungicides itraconazole

and posaconazole. Biochem. Pharmacol. 130, 93-103 (2017).

Akram M, Waratchareeyakul W, Haupenthal J, Hartmann RW, Schuster

D. Pharmacophore modeling and in silico/in vitro screening for human

cytochrome P450 11B1 & cytochrome P450 11B2 inhibitors. Front.

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Ahammer L, Grutsch S, Kamenik AS, Liedl KR, Tollinger M. Structure of

the Major Apple Allergen Mal d 1. J. Agric. Food Chem. 65(8), 1606-12

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M. Miconidin Acetate and Primin as Potent 5-Lipoxygenase Inhibitors

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Wang Y, Gkeka P, Fuchs JE, Liedl KR, Cournia Z. DPPC-cholesterol

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Waltenberger B, Atanasov AG, Heiss EH, Bernhard D, Rollinger JM,

Breuss JM, Schuster D, Bauer R, Kopp B, Franz C. Drugs from nature

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Heinz K, Arnhard K, Laufer G, Grimm M. Leoligin, the major lignan

from Edelweiss, inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase

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Kramer C, Mochalski P, Unterkofler K, Agapiou A, Ruzsanyi V, Liedl KR.

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Kaserer T, Rigo R, Schuster P, Alcaro S, Sissi C, Schuster D. Optimized virtual

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Journal of chemical information and modeling 56(3), 484-500 (2016).

Kaserer T, Obermoser V, Weninger A, Gust R, Schuster D. Evaluation

of selected 3D virtual screening tools for the prospective identification

of peroxisome proliferator-activated receptor (PPAR) γ partial agonists.

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Kaserer T, Lantero A, Schmidhammer H, Spetea M, Schuster D. µ Opi-

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Beck KR, Sommer TJ, Schuster D, Odermatt A. Evaluation of tetrabro-

mobisphenol A effects on human glucocorticoid and androgen recep-

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Bachmann VA, Mayrhofer JE, Ilouz R, Tschaikner P, Raffeiner P, Röck R,

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Schweiger S, Matthes F, Posey K, Kickstein E, Weber S, Hettich MM,

Pfurtscheller S, Ehninger D, Schneider R, Krauß S. Resveratrol induces

dephosphorylation of Tau by interfering with the MID1-PP2A complex.

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Schindler S, Missbichler B, Walther C, Sponring M, Cserjan-Puschmann

M, Auer B, Schneider R, Dürauer A. Npro fusion technology: On-column

complementation to improve efficiency in biopharmaceutical produc-

tion. Protein Expr. Purif. 120, 42-50 (2016).

Lemmermeyer T, Lamp B, Schneider R, Ziebuhr J, Tekes G, Thiel H-J.

Characterization of monoclonal antibodies against feline coronavirus

accessory protein 7b. Vet. Microbiol. 184, 11-19 (2016).

J. Striessnig, N. Singewald, A. Koschak

Adori C, Barde S, Vas S, Ebner K, Su J, Svensson C, Mathé AA, Singewald

N, Reinscheid RR, Uhlén M, Kultima K, Bagdy G, Hökfelt T. Exploring

the role of neuropeptide S in the regulation of arousal: a functional

anatomical study. Brain Struct. Funct. 221, 3521-3546 (2016).

Mesirca P, Bidaud I, Briec F, Evain S, Torrente AG, Le Quang K, Mangoni

ME. G protein-gated IKACh channels as therapeutic targets for treat-

ment of sick sinus syndrome and heart block. Proc. Natl. Acad. Sci. USA

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Puschban Z, Sah A, Grutsch I, Singewald N, Dechant G. Reduced Anx-

iety-Like Behavior and Altered Hippocampal Morphology in Female

p75NTR(exon IV-/-) Mice. Front. Behav. Neurosci. 10, 103 (2016).

Sartori SB, Maurer V, Murphy C, Schmuckermair C, Muigg P, Neu-

mann ID, Whittle N, Singewald N. Combined neuropeptide S and

D-cycloserine augmentation prevents the return of fear in extinction

impaired rodents: advantage of dual vs. single drug approaches. Int. J.

Neuropsychopharmacol. 19, 1-11 (2016).

Schaufler J, Ronovsky M, Savalli G, Cabatic M, Sartori SB, Singewald N,

Pollak DD. Fluoxetine normalizes disrupted light-induced entrainment

fragmented ultradian rhythms and altered hippocampal clock gene

expression in an animal model of high trait anxiety- and depression-

related behavior. Ann. Med. 48, 17-27 (2016).

Stanika R, Campiglio M, Pinggera A, Lee A, Striessnig J, Flucher BE,

Obermair GJ. Splice variants of the Cav1.3 L-type calcium channel regu-

late dendritic spine morphology. Sci. Rep. 6, 34528 (2016).

Sultana N, Dienes B, Benedetti A, Tuluc P, Szentesi P, Sztretye M, Rainer

J, Hess MW, Schwarzer C, Obermair GJ, Csernoch L, Flucher BE. Restrict-

ing calcium currents is required for correct fiber type specification in

skeletal muscle. Development 143, 1547-1559 (2016).

Torrente AG, Mesirca P, Neco P, Rizzetto R, Dubel S, Barrere C, Sinneg-

ger-Brauns M, Striessnig J, Richard S, Nargeot J, Gomez AM, Mangoni

ME. L-type Cav1.3 Channels Regulate Ryanodine receptor-dependent

calcium release during sino-atrial node pacemaker activity. Cardiovasc.

Res. 109, 451-61 (2016).

Tuluc P, Benedetti B, Coste de Bagneaux P, Grabner M, Flucher BE. Two

distinct voltage-sensing domains control voltage sensitivity and kinetics

of current activation in CaV1.1 calcium channels. J. Gen. Physiol. 147,

437 (2016).

Tuluc P, Yarov-Yarovoy V, Benedetti B, Flucher BE. Molecular Interac-

tions in the Voltage Sensor Controlling Gating Properties of CaV

Calcium Channels. Structure 24, 261-271 (2016).

Whittle N, Maurer V, Murphy C, Rainer J, Bindreither D, Hauschild M,

Scharinger A, Oberhauser M, Keil T, Brehm C, Valovka T, Striessnig J,

Singewald N. Enhancing dopaminergic signaling and histone acetyla-

tion promotes long-term rescue of deficient fear extinction. Transl.

Psychiatry 6, e974 (2016).

Wille A, Amort T, Singewald N, Sartori SB, Lusser A. Dysregulation of se-

lect ATP-dependent chromatin remodeling factors in high trait anxiety.

Behav. Brain Res. 311, 141-146 (2016).

Härtner L, Keil TWM, Kreuzer M, Fritz EM, Wenning GK, Stefanova N,

Fenzl T. Distinct Parameters in the EEG of the PLP α-SYN Mouse Model

for Multiple System Atrophy Reinforce FaceValidity. Front. Behav. Neu-

rosci. 10, 252 (2017).

Martínez-Rivera A, Hao J, Tropea TF, Giordano TP, Kosovsky M, Rice RC,

Lee A, Huganir RL, Striessnig J, Addy NA, Han S, Rajadhyaksha AM. En-

hancing VTA Cav13 L-type Ca2+ channel activity promotes cocaine and

mood-related behaviors via overlapping AMPA receptor mechanisms in

the nucleus accumbens. Mol. Psychiatry 22, 1735-1745 (2017).

Mastrolia V, Flucher SM, Obermair GJ, Drach M, Hofer H, Renström E,

Schwartz A, Striessnig J, Flucher BE, Tuluc P. Loss of α2δ-1 Calcium Chan-

nel Subunit Function Increases the Susceptibility for Diabetes. Diabetes

66, 867-907 (2017).

Monteleone Stefania, Lieb Andreas, Pinggera Alexandra, Negro Giulia,

Fuchs Julian E, Hofer Florian, Striessnig Jörg, Tuluc Petronel, Liedl Klaus

R. Mechanisms Responsible for ω-Pore Currents in Cav Calcium Channel

Voltage-Sensing Domains. Biophys. J. 113, 1485-1495 (2017).

Ortner NJ, Bock G, Dougalis A, Kharitonova M, Duda J, Hess S, Tuluc T,

Pomberger T, Stefanova N, Pitterl F, Ciossek T, Oberacher H, Draheim

HJ, Kloppenburg P, Liss B, Striessnig J. Lower Affinity of Isradipine for

L-Type Ca2+ Channels during Substantia Nigra Dopamine Neuron-like

Activity: Implications for Neuroprotection in Parkinson’s Disease. J.

Neurosci. 37, 6761-6777 (2017).

Pinggera A, Mackenroth L, Rump A, Schallner J, Beleggia F, Wollnik B,

Striessnig J. New Gain-of-Function Mutation Shows CACNA1D as Recur-

rently Mutated Gene in Autism Spectrum Disorders and Epilepsy. Hum.

Mol. Genet. 26, 2923-2932 (2017).

Tan GC, Negro G, Pinggera A, Tizen Laim NMS, Rose I, Ceral J, Ryska

A, Chin LK, Kamaruddin NA, Mohd Mokhtar N, A Jamal AR, Sukor N,

Solar M, Striessnig J, Brown MJ, Azizan EA. Aldosterone-Producing

Adenomas: Histopathology-Genotype Correlation and Identification of

a Novel CACNA1D Mutation. Hypertension 70, 129-136 (2017).

Toyoda F, Mesirca P, Dubel S, Ding W-G, Striessnig J, Mangoni ME,

Matsuura H. CaV13 L-type Ca2+ channel contributes to the heartbeat

by generating a dihydropyridine-sensitive persistent Na+ current. Sci.

Rep. 7, 7869 (2017).

Alexander SP, Striessnig J, Kelly E, Marrion NV, Peters JA, Faccenda

E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP

Collaborators. THE CONCISE GUIDE TO PHARMACOLOGY 2017/18:

Voltage-gated ion channels. Br. J. Pharmacol. 174 (Suppl 1) S160-S194

(2017).

Alexander SP, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD,

Pawson AJ, Sharman JL, Southan C, Buneman OP, Cidlowski JA, Christo-

poulos A, Davenport AP, Fabbro D, Spedding M, Striessnig J, Davies JA;

CGTP Collaborators.THE CONCISE GUIDE TO PHARMACOLOGY 2017/18:

Overview. Br. J. Pharmacol. 174 (Suppl 1) S1-S16 (2017).

Ortner NJ, Striessnig J. L-type calcium channels as drug targets in CNS

disorders. Channels (Austin) 10, 7-13 (2016).

Pinggera A, Striessnig J. Cav 1.3 (CACNA1D) L-type Ca2+ channel dys-

function in CNS disorders. J. Physiol. 594, 5839-5849 (2016).

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Striessnig J. Voltage-gated calcium channels - from basic mechanisms to

disease. J. Physiol. 594, 5817-5821 (2016).

Sartori BS, Singewald N. Neue pharmakologische Strategien zur Aug-

mentation von Extinktionslernen in der Angsttherapie. Neuroforum

23, 197-211 (2017).

Sartori BS, Singewald N. New pharmacological strategies for augment-

ing extinction learning in anxiety disorders. Neuroforum 23, A145-A156

(2017).

Seitter H, Koschak A. Relevance of tissue specific subunit expression in

channelopathies. Neuropharmacology 17, 30302-7 (2017).

Ebner K, Singewald N. Individual differences in stress susceptibility and

stress inhibitory mechanisms. Current Opinion in Behavioral Sciences

14, 54-64 (2017).

Murphy CP, Singewald N. Potential of microRNAs as novel targets in

the alleviation of pathological fear. Genes Brain Behav, doi: 10.1111/

gbb.12427. [Epub ahead of print]

Striessnig, Jörg: Editorial Board - Channels, 01.01.2007 lfd.

Singewald, Nicolas: Editor - Amino Acids, 01.01.1999 lfd.

H. Stuppner, M. Ganzera

Dreier D, Latkolik S, Rycek L, Schnürch M, Dymáková A, Atanasov AG,

Ladurner A, Heiss EH, Stuppner H, Schuster D, Mihovilovic MD, Dirsch

VM. Linked magnolol dimer as a selective PPARγ agonist – Structure-

based rational design, synthesis, and bioactivity evaluation. Sci. Rep. 7,

13002 (2017).

Gvazava L, Gorgaslidze N, Ganzera M, Skhirtladze A. A new lupane

triterpene glycoside from Euphorbia boissierana Prokh. Trends in Phy-

tochemical Research 1, 149-152 (2017).

Haller J, Schwaiger S, Stuppner H, Gafner F, Ganzera M. Isolation of

Three Triterpene Saponins, Including Two New Oleanane Derivatives,

from Soldanella alpina and Hydrophilic Interaction Liquid Chromatog-

raphy-Evaporative Light Scattering Detection of these Three Saponins

in Four Soldenella Species. Phytochemical Anal. 28, 567-574 (2017).

Hartmann A, Murauer A, Ganzera M. Quantitative analysis of mycospo-

rine-like amino acids in marine algae by capillary electrophoresis with

diode-array detection. J. Pharm. Biomed. Anal. 138, 153-157 (2017).

Hochleitner J, Akram M, Ueberall M, Davis RA, Waltenberger B,

Stuppner H, Sturm S, Ueberall F, Gostner JM, Schuster D. A combinato-

rial approach for the discovery of cytochrome P450 2D6 inhibitors from

nature. Sci. Rep. 7, 8071 (2017).

Kemertelidze E, Skhirthladze M, Ganzera M. Furostanol and triterpene

saponins from the roots of Digitalis ciliata. Chemistry of Natural Com-

pounds 53, 492-496 (2017).

Khan SY, Awad EM, Oszwald A, Mayr M, Yin X, Waltenberger B,

Stuppner H, Lipovac M, Pavel U, Breuss JM. Premature senescence of

endothelial cells upon chronic exposure to TNFα can be prevented by

N-acetyl cysteine and plumericin. Sci. Rep. 7, 39501 (2017).

Mailainer C, Schachner D, Sangiovanni E, Atanasov AG, Schwaiger S,

Stuppner H, Heiss EH, Dirsch VM. Eurycomalactone Inhibits Expression

of Endothelial Adhesion Molecules at a Post-Transcriptional Level. J.

Nat. Prod. 80, 3186-3193 (2017).

Marzocco S, Adesso S, Alilou M, Stuppner H, Schwaiger S. Anti-Inflam-

matory and Anti-Oxidant Potential of the Root Extract and Constituents

of Doronicum austriacum. Molecules 22, 1003 (2017).

Murauer A, Bakry R, Schottenberger H, Huck CW, Ganzera M. An in-

novative monolithic zwitterionic stationary phase for the separation of

phenolic acids in coffee bean extracts by capillary electrochromatogra-

phy. Anal. Chim. Acta 963, 136-142 (2017).

Murauer A, Ganzera M. Quantitative Determination of Lactones in

Piper methysticum (Kava-Kava) by Supercritical Fluid Chromatography.

Planta Med. 83, 1053-1057 (2017).

Nebieridze VG, Skhirtladze AV, Kemertelidze EP, Ganzera M. Nucleo-

sides from Tribulus terrestris. Chemistry of Natural Compounds 53,

1010-1011 (2017).

Nicolaus C, Junghanns S, Hartmann A, Murillo R, Ganzera M, Merfort I.

In vitro studies to evaluate the wound healing properties of Calendula

officinalis extracts. J. Etnopharmacol. 196, 94-103 (2017).

Pataczek L, Cheilari A, Zikeli S, Sturm S, Stuppner H, Gruber S. Cen-

taurium erythraea Cultivation Method for Optimal Yield and Product

Quality. Journal of Herbs, Spices & Medicinal Plants 23, 193-215 (2017).

Peduto A, Scuotto M, Krauth V, Roviezzo F, Rossi A, Temml V, Esposito V,

Stuppner H, Schuster D, D´Agostino B., Schiraldi C, De Rosa M, Werz O,

Filosa R. Optimization of benzoquinone and hydroquinone derivatives

as potent inhibitors of human 5-lipoxygenase. Eur. J. Med. Chem. 127,

715-726 (2017).

Schäfer S, Schwaiger S, Stuppner H. Aristolic Acid Derivates from the

Bark of Antidesma ghaesembilla. Planta Med. 83, 1097-1102 (2017).

Siewert B, Langerman M, Hontani Y, Kennis JTM, Van Rixel VHS, Lim-

burg B, Siegler MA, Saez Talens V, Kieltyka RE, Bonnet S. Turning on

the red phosphorescence of a [Ru(tpy)(bpy)(Cl)]Cl complex by amide

substitution: self-aggregation, toxicity, and cellular localization of an

emissive ruthenium-based amphiphile. Chemical Commun. 53, 11126-

11129 (2017).

Skhirtladze A, Nebieridze V, Benidze M, Kemertelidze E, Ganzera M.

Furostanol glycosides from the roots of Tribulus terrestris L. Bulletin of

the Georgian National Academy of Sciences 11, 122-126 (2017).

Skhirtladze AV, Kopaliani TA, Nebieridze VG; Kemertelidze EP, Ganzera

M. New steroidal glycosides from pericarp of Digitalis ferruginea.

Chemistry of Natural Compounds 53, 1083-1087 (2017).

Taibon J, Sturm S, Strasser H, Stuppner H. Combination of a QuEChERS-

based extraction protocol with a fast and selective UHPLC-QTOF-MS

assay for the detection and quantification of Metarhizium brunneum

metabolites from honey samples. SOJ Pharmacy & Pharmaceutical Sci-

ences 4, 1-5 (2017).

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Temml V, Garscha U, Romp E, Schubert G, Gerstmeier J, Kutil Z, Ma-

tuszczak B, Waltenberger B, Stuppner H, Werz O, Schuster D. Discovery

of the first dual inhibitor of the 5-lipoxygenase-activating protein and

soluble epoxide hydrolase using pharmacophore-based virtual screen-

ing. Sci. Rep. 7, 42751 (2017).

Vrabl P, Schinagl CW, Artmann DJ, Krüger A, Ganzera M, Pötsch A,

Burgstaller W. The Dynamics of Plasma Membrane, Metabolism and

Respiration (PM-M-R) in Penicillium ochrochloron CBS 123824 in

Response to Different Nutrient Limitations—A Multi-level Approach

to Study Organic Acid Excretion in Filamentous Fungi. Frontiers in

Microbiol. 8, 2475 (2017).

Vuorinen A, Engeli RT, Leugger S, Bachmann F, Akram M, Atanasov AG,

Waltenberger B, Temml V, Stuppner H, Krenn L, Ateba SB, Njamen D,

Davis RA, Odermatt A, Schuster D. Potential Antiosteoporotic Natural

Product Lead Compounds That Inhibit 17β-Hydroxysteroid Dehydroge-

nase Type 2. J. Nat. Prod. 80, 965-974 (2017).

Alsabil K, Suor-Cherer S, Koeberle A, Viault G, Lavaud A, Temml V,

Waltenberger B, Schuster D, Litaudon M, Lorkowski S, de Vaumas R,

Helesbeux JJ, Guilet D, Stuppner H, Werz O, Seraphin D, Richomme P.

Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1

Inhibitors. Planta Med. 82, 1110-1116 (2016).

Antal DS, Pinzaru I, Borcan F, Marti TD, Ledeti I, Coricovac D, Schwaiger

S, Stuppner H, Dehelean CA, Ollivier E, Soica C. Inclusion Complexes of

the Aurone Sulfuretin and the Chalcone Butein from Cotinus coggygria

Wood in Two Cyclodextrin Types: First data on physico-chemical proper-

ties. Revista De Chimie 67, 1104-1109 (2016).

Becker K, Hartmann A, Ganzera M, Fuchs D, Gostner JM. Immuno-

modulatory Effects of the Mycosporine-Like Amino Acids Shinorine and

Porphyra-334. Mar. Drugs 14, 119 (2016).

Cheilari A, Sturm S, Intelmann D, Seger C, Stuppner H. Head-to-Head

Comparison of Ultra-High-Performance Liquid Chromatography with

Diode Array Detection versus Quantitative Nuclear Magnetic Resonance

for the Quantitative Analysis of the Silymarin Complex in Silybum mari-

anum Fruit Extracts. J. Agric. Food Chem. 64, 1618-1626 (2016).

Hartmann A, Holzinger A, Ganzera M, Karsten U. Prasiolin, a new

UV-sunscreen compound in the terrestrial green macroalga Prasiola

calophylla (Carmichael ex Greville) Kützing (Trebouxiophyceae, Chlo-

rophyta). Planta 243, 161-169 (2016).

Heiss EH, Liu R, Waltenberger B, Khan S, Schachner D, Kollmann P, Zim-

mermann K, Cabaravdic M, Uhrin P, Stuppner H, Breuss JM, Atanasov

AG, Dirsch VM. Plumericin inhibits proliferation of vascular smooth

muscle cells by blocking STAT3 signaling via S-glutathionylation. Sci.

Rep. 6, 20771 (2016).

Papadakis ES, Robson N, Yeomans A, Bailey S, Laversin S, Beer S, Sayan

A, Ashton-Key M, Schwaiger S, Stuppner H, Troppmair J, Packham

G, Cutress R. A combination of trastuzumab and BAG-1 inhibition

synergistically targets HER2 positive breast cancer cells. Oncotarget 7,

18851-18864 (2016).

Papadakis ES, Barker CR, Syed H, Reeves T, Schwaiger S, Stuppner H,

Troppmair J, Blaydes JP, Cutress RI. The Bag-1 inhibitor, Thio-2, reverses

an atypical 3D morphology driven by Bag-1L overexpression in a MCF-

10A model of ductal carcinoma in situ. Oncogenesis 5, e215 (2016).

Pfeifer I, Murauer A, Ganzera M. Determination of coumarins in the

roots of Angelica dahurica by supercritical fluid chromatography. J.

Pharm. Biomed. Anal. 129, 246-251 (2016).

Schäfer S, Salcher S, Seiter M, Ranninger C, Moest M, Obexer P, Huber

CG, Ausserlechner MJ, Schwaiger S, Stuppner H. Characterization of

the XIAP-Inhibiting Proanthocyanidin Fraction of the Aerial Parts of

Ephedra sinica. Planta Med. 82, 973-985 (2016).

Schaible AM, Filosa R, Krauth V, Temml V, Pace S, Garscha U, Liening S,

Weinigel C, Rummler S, Schieferdecker S, Nett M, Peduto A, Collarile

S, Scuotto M, Roviezzo F, Spaziano G, De Rosa M, Stuppner H, Schuster

D, D´Agostino B, Werz O. The 5-lipoxygenase inhibitor RF-22c potently

suppresses leukotriene biosynthesis in cellulo and blocks bronchocon-

striction and inflammation in vivo. Biochem. Pharmacol. 112, 60-71

(2016).

Scharinger B, Messner B, Türkcan A, Schuster D, Vuorinen A, Pitterl F,

Heinz K, Arnhard K, Laufer G, Grimm M, Stuppner H, Oberacher H,

Eller P, Ritsch A, Bernhard D. Leoligin, the major lignan from edelweiss,

inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase and reduces choles-

terol levels in ApoE −/− mice. J. Mol. Cell. Cardiol. 99, 35-46 (2016).

Skhirtladze A, Kemertelidze E, Nebieridze V, Ganzera M. Phenyletha-

noid Glycosides from the Roots of Digitalis ciliata Trautv. Helvetica

Chimica Acta 99, 241-245 (2016).

Waltenberger B, Garscha U, Temml V, Liers J, Werz O, Schuster D,

Stuppner H. Discovery of Potent Soluble Epoxide Hydrolase (sEH) Inhibi-

tors by Pharmacophore-Based Virtual Screening. Journal of Chemical

Information and Modeling 56, 747-762 (2016).

Wang L, Ladurner A, Latkolik S, Schwaiger S, Linder T, Hosek J, Palme V,

Schilcher N, Polansky O, Heiss EH, Stangl H, Mihovilovic MD, Stuppner

H, Dirsch VM, Atanasov AG. Leoligin, the Major Lignan from Edelweiss

(Leontopodium nivale subsp. alpinum), Promotes Cholesterol Efflux

from THP-1 Macrophages. J. Nat. Prod. 79, 1651-1657 (2016).

Winderl B, Schwaiger S, Ganzera M. Fast and improved separation of

major coumarins in Ammi visnaga (L.) Lam. by Supercritical Fluid Chro-

matography. J. Sep. Sci. 39, 4042-4048 (2016).

Zatelli GA, Temml V, Kutil Z, Landa P, Vanke T, Schuster D, Falkenberg

M. Miconidin Acetate and Primin as Potent 5-Lipoxygenase Inhibitors

from Brazilian Eugenia hiemalis (Myrtaceae). Planta Medica Letters 3,

e17-e19 (2016).

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M. Tollinger, C. Kreutz

Juen MA, Wunderlich CH, Nussbaumer F, Tollinger M, Kontaxis G, Kon-

rat R, Hansen DF, Kreutz CK. Excited states of nucleic acids probed by

proton relaxation dispersion NMR Spectroscopy. Angew. Chem. Int. Ed.

Engl. 55, 12008-12012 (2016).

Moschen T, Grutsch S, Juen, MA, Wunderlich CH, Kreutz C, Tollinger M.

Measurement of ligand-target residence times by 1H relaxation disper-

sion NMR spectroscopy. J. Med. Chem. 59, 10788-10793 (2016).

Zhou H, Kimsey IJ, Nikolova EN, Sathyamoorthy B, Grazioli G, McSally

J, Bai T, Wunderlich CH, Kreutz C, Andricioaei I, Al-Hashimi HM. M(1)A

and m(1)G disrupt A-RNA structure through the intrinsic instability of

Hoogsteen base pairs. Nat. Struct. Mol. Biol. 23, 803-810 (2016).

Grutsch S, Brüschweiler S, Tollinger M. NMR methods to study dynamic

allostery. PLoS Comput. Biol. 12, e1004620 (2016).

Machado Y, Freier R, Scheiblhofer S, Thalhamer T, Mayr M, Briza P,

Grutsch S, Ahammer L, Fuchs J, Wallnöfer H, Isakovic A, Kohlbauer V,

Hinterholzer A, Steiner M, Danzer M, Horejs-Hoeck J, Ferreira F, Liedl

KR, Tollinger M, Lackner P, Johnson CM, Brandstetter H, Thalhamer

J, Weiss R. Fold-stability during endolysosomal acidification is a key

factor for allergenicity and immunogenicity of the major birch pollen

allergen. J. Allergy Clin. Immunol. 137, 1525-1534 (2016).

Duchardt-Ferner E, Juen M, Kreutz C, Wöhnert J. NMR resonance as-

signments for the tetramethylrhodamine binding RNA aptamer 3 in

complex with the ligand 5-carboxy-tetramethylrhodamine. Biomol.

NMR Assign. 11, 29-34 (2016).

Ahammer L, Grutsch S, Tollinger M. NMR resonance assignments of the

major apple allergen Mal d 1. Biomol. NMR Assign. 10, 287-290 (2016).

Ren A, Vusurovic N, Gebetsberger J, Gao P, Juen M, Kreutz C, Micura

R, Patel DJ. Pistol ribozyme adopts a pseudoknot fold facilitating site-

specific in-line cleavage. Nat. Chem. Biol. 12, 702-708 (2016).

Scherl M, Müller T, Kreutz C, Huber RG, Zass E, Liedl KR, Kräutler B.

Chlorophyll catabolites in fall leaves of the wych elm tree present a

novel glycosylation motif. Chemistry 22, 9498-9503 (2016).

Longhini AP, LeBlanc RM, Becette O, Salguero C, Wunderlich CH, John-

son BA, D’Souza VM, Kreutz C, Dayie TK. Chemo-enzymatic synthesis of

site-specific isotopically labeled nucleotides for use in NMR resonance

assignment, dynamics and structural characterizations. Nucleic Acids

Res. 44, e52 (2016).

Ahammer L, Grutsch S, Kamenik AS, Liedl KR, Tollinger M. Structure of

the major apple allergen Mal d 1. J. Agric. Food Chem. 65, 1606-1612

(2017).

Nussbaumer F, Juen M, Gasser C, Kremser J, Mueller T, Tollinger M,

Kreutz CK. Synthesis and incorporation of 13C-labeled DNA building

blocks to probe structural dynamics of DNA by NMR. Nucleic Acids Res.

45, 9178-9192 (2017).

Kremser J, Strebitzer E, Plangger R, Juen MA, Nußbaumer F, Glasner H,

Breuker K, Kreutz C. Chemical synthesis and NMR spectroscopy of long

stable isotope labelled RNA. Chem. Commun. 53, 12938-12941 (2017).

Rennella E, Sara T, Juen M, Wunderlich C, Imbert L, Solyom Z, Favier A,

Ayala I, Weinhaeupl K, Schanda P, Konrat R, Kreutz C, Brutscher B. RNA

binding and chaperone activity of E. coli cold-shock protein CspA. Nucl.

Acids Res. 45, 4255-4268 (2017).

Grutsch S, Fuchs JE, Ahammer L, Kamenik AS, Liedl KR, Tollinger M.

Conformational flexibility differentiates naturally occurring Bet v 1

isoforms. Int. J. Mol. Sci. 18, 1192 (2017).

Ahammer L, Grutsch S, Wallner M, Ferreira F, Tollinger M. NMR reso-

nance assignments of a hypoallergenic isoform of the major birch pol-

len allergen Bet v 1. Biomol. NMR Assign. 11, 231-234 (2017).

Neuner S, Kreutz C, Micura R. The synthesis of 15N7-Hoogsteen face-

labeled adenosine amidite for solid phase RNA synthesis. Monatsh.

Chem. 148, 149-155 (2017).

Wolter AC, Weickhmann AK, Nasiri AH, Hantke K, Ohlenschläger O,

Wunderlich CH, Kreutz C, Duchardt-Ferner E, Wöhnert J. A Stably Pro-

tonated Adenine Nucleotide with a Highly Shifted pKa Value Stabilizes

the Tertiary Structure of a GTP-Binding RNA Aptamer. Angew. Chem.

Int. Ed. Engl. 56, 401-404 (2017).

Tants JN, Fesser S, Kern T, Stehle R, Geerlof A, Wunderlich CH, Juen MA,

Hartlmüller C, Böttcher R, Kunzelmann S, Lange O, Kreutz C, Förste-

mann K, Sattler M. Molecular basis for asymmetry sensing of siRNAs by

the Drosophila Loqs-PD/Dcr-2 complex in RNA interference. Nucl. Acids

Res. 45, 12536-12550 (2017).

Vuorinen A, Engeli RT, Leugger S, Kreutz C, Schuster D, Odermatt

A, Matuszczak B. Phenylbenzenesulfonates and -sulfonamides as

17β-hydroxysteroid dehydrogenase type 2 inhibitors: Synthesis and

SAR-analysis. Bioorg. Med. Chem. Lett. 27, 2982-2985 (2017).

Führer S, Ahammer L, Ausserbichler A, Scheffzek K, Dunzendorfer-Matt

T, Tollinger M. NMR resonance assignments of the EVH1 domain of

Neurofibromin’s recruitment factor Spred1. Biomol. NMR Assign. 11,

305-308 (2017).

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CMBI - careers of young researchers

CMBI news

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t | Daniela Schuster was awarded one of the first two Ingeborg Hochmair

Professorships by the University of Innsbruck. This temporary professor-

ship is awarded to highly successful, young female scientists to increase

the number of female professors in faculties, where female scientists

are underrepresented. This position should also help the awardees to be

appointed full professors at other institutions. In 2018, Daniela Schuster

follows a call as Professor for Pharmaceutical and Medicinal Chemistry at

the Paracelsus Medical Private University of Salzburg. Together with her

team, she will build up teaching courses and infrastructure for the newly

established pharmacy study and continue her research on in silico acti-

vity profiling, especially in the field of environmental chemical toxicity.

Jerome Mertens joined the Institute of Molecular

Biology in 2017 starting his tenure track, and is

currently building his research group at the De-

partment for Genomics, Stem Cell Biology and

Regenerative Medicine. Dr. Mertens is also con-

ducting his research as a staff scientist at the Salk

Institute for Biological Studies in La Jolla, CA, USA.

His work combines human neural cell reprogram-

ming technologies such as the direct neuronal conversion (iN) with next-

generation sequencing strategies, bioinformatics, neuronal cell biology

and functional neuroscience. With a focus on age-related neurodege-

nerative diseases and neuropsychiatric disorders, his goal is to unravel

the impact of epigenetic cellular states on neuronal pathology, and to

direct the interphase between aging and disease. In 2017, he has been

awarded the prestigious K99 Pathway to Independence award from the

National Institute for Aging.

94 95 CMBI news

CMBI - careers of young researchers

CMBI news

CM

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cho

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hip

s | David Granig (Simone B. Sartori and Nicolas

Singewald Group, Institute of Pharmacy,

Department of Pharmacology and Toxicology):

Discovery and characterization of non-

peptidergic neuropeptide S receptor agonists as

potential novel anxiolytics

In collaboration with the Dept. of Pharmacognosy

(Prof. Stuppner, Dr. Schwaiger) four derivatives of our previously

identified potential neuropeptide S receptor (NPSR) agonist were

synthesized in house, virtually screened (Prof. Daniela Schuster,

Dept. Pharmaceutical Chemistry) and characterized in-vitro using

a refined cell-based Ca2+-mobilization assay. The parent compound

and its two dimethyl- and diethyl-derivatives demonstrate specific

agonistic properties at the NPSR with moderate efficacy. Since these

two derivatives are suggested to display BBB penetrance, they

represent leads for the development of small NPSR agonists which are

expected to display similar unique characteristics as the parent NPS,

namely to induce anxiolytic effects without any signs of sedation. The

collaborations are ongoing in terms of refining the pharmacophore

model, the synthesis of derivatives and in vivo testing for potential

therapeutic effects.

Anna Hausruckinger (Frank Edenhofer Group,

Department of Molecular Biology): CaV expression

in neurons derived from human iPS cells

Voltage-gated calcium channels (CaVs) are

involved in the regulation of various neuronal

functions in the central nervous system, such as

neurotransmitter secretion, postsynaptic signal

integration and neuronal plasticity. Current research mainly depends

on the analyses of heterologous expression systems (such as HEK cells)

or primary animal neurons that are far from being ideal to correlate

with the physiology of human neurons. Induced pluripotent stem (iPS)

cells represent a promising alternative source of human neurons. The

overall aim of the project is to elaborate on an expression analysis

of CaVs subunits in neurons derived from human iPS cells. Moreover,

we investigate to which extent the modulation of CaV functionality

by subunit overexpression will impact on the maturation and

synaptogenesis of in vitro differentiated neurons.

In 2013, the CMBI initiated an annual call for a young investigator

scholarship. Aim of this scholarship is to support a young career

(Master/PhD level) and to strengthen collaboration within the CMBI

by selecting a candidate, who is engaged in a high-profile research

project connecting two or more CMBI member groups. The scholar and

his project are supported by allocating prize money for expendable

materials and consumables.

Previous CMBI Scholars:

2013: R. Spitzer

(Christoph Kreutz Group, Department of Organic Chemistry)

2014: Johanna E. Mayrhofer

(Eduard Stefan Group, Department of Biochemistry)

2015: Julian Wimmer (Ilse Kranner, Department of Botany)

2016: Florian Enzler (Eduard Stefan, Department of Biochemistry)

The current CMBI Scholars for 2017:

96 97 Awards and honors for CMBI scientists Awards and honors for CMBI scientists

Awards and honors for CMBI scientists

Linda Ahammer, Department of Organic Chemistry:

"Young Investigator Award" at the 27th ICMRBS in Kyoto, Japan,

August 2016.

Erwann Arc, Department of Botany:

Best lecture of an early career scientist, 21th meeting of the ATSPB,

Berchtesgaden, 2016

Giorgia Baraldo, Research Department for Biomedical Aging

Research:

Grant D. Swarovski AG, “Plant-derived compounds for inhibition of

NOX4 to counteract vascular aging”

Giovanni Calderisi, Department of Organic Chemistry:

Student Travel Award of the American Society for Mass

Spectrometry for presentation of a poster at the 65th ASMS

conference, Indianapolis, IN, USA (2017)

Andreas Friedl, Department of Pharmacognosy:

Meda Preis für Phytopharmaka-Forschung 2016

Sebastian Führer, Department of Organic Chemistry:

GÖCH-Förderungspreis für die besten Diplomarbeiten (Gesellschaft

Österreichischer Chemiker), Austria, 2017 Innsbruck 2017.

Marco Grasse, Research Department for Biomedical Aging Research:

Grant D. Swarovski AG 2017, “Effects of GM-CSF application

during tetanus/diphtheria vaccination on the antigen-specific T cell

response in vivo”

Katharina Günther, Department of Molecular Biology:

Poster Prize, 9th ÖGMBT Annual Meeting & 8th Life Science Meeting,

"Molecular and cellular mechanisms of human diseases". Innsbruck, 2017

Nadja Hofer, Department of Pharmacology and Toxicology:

Würdigungspreis Bundesministerium für Wissenschaft, Forschung

und Wirtschaft (2016)

Ilse Kranner, Department of Botany

President of the ATSPB (Austrian Society of Plant Biology) and

national delegate on the FESPB (Federation of European Societies

of Plant Biology) Council

Johannes Kremser, Department of Organic Chemistry:

"Suraj Manrao Poster Award" at the 20th ISMAR in Quebec City,

Canada, July 2017.

Birgit Lengerer, Department of Zoology

Best Poster Award (3rd Place), Life Science PhD Meeting Innsbruck 2017

Carina Miggitsch, Research Department for Biomedical

Aging Research:

Best Short Talk Award, Life Science PhD Meeting Innsbruck 2017

Simon Moosmang, Department of Pharmacognosy:

Young Talent Poster Award, First Place - Best Poster, VASCage

Meeting, 2017

Sandro Neuner, Department of Organic Chemistry

Best Paper Award 2017, Monatshefte für Chemie/Chemical Monthly,

Springer

Michael Neustetter, Department of Ion Physics and Applied Physics:

Award of Excellence of the Austrian Federal Ministry of Science and

Research (2017).

Nadine Ortner, Department of Pharmacology and Toxicology:

Principality of Liechtenstein Prize (2017)


Jubiläumsfonds der Universität Innsbruck und der Medizinischen

Universität Innsbruck zur Förderung wissenschaftlicher

Kooperationsprojekte (2017)


ALUMNI-I-MED Talk Prize, Life Science PhD Meeting (2017)

Luca Pangrazzi, Research Department for Biomedical

Aging Research:

Grant D. Swarovski AG 2016, “Characterization of niche providing

cells in the bone marrow”

awar

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Erwann Arc

Marco Grasse Luca Pangrazzi

Ilse Kranner

Sebastian Führer, 17. Österreichische Chemietage,

Univ. Salzburg (2017), Foto: Göch

The successful scientific activities of the CMBI are reflected in numerous

awards and honors received from several members during the reporting

period.

Katharina Günther

98 99

Isabella Pfeifer, Department of Pharmacognosy:

Meda Preis für Phytopharmaka-Forschung 2017

Michael Schauperl, Department of General, Inorganic and

Theoretical Chemistry:

Dr. Otto Seibert Science Award, 11/2017

Michael Schauperl, Department of General, Inorganic and


Science Award 2017 of the Tyrolean Economic Chamber, 11/2017

Daniela Schuster, Department of Pharmaceutical Chemistry:

Ingeborg Hochmair Professorship 2016

Daniela Schuster, Department of Pharmaceutical Chemistry:

Poster award (2nd rank) at Pharma 2030

Torsten Schwerte, Department of Zoology:

Edmund Optics Educational Award Winner in Europe (2017)

Anita Siller, Department of Pharmacology and Toxicology:

Studienförderpreis des Deutschen Freundeskreises der

Universitäten in Innsbruck e. V. (2016)


Best Poster Award, 9th ÖGMBT Annual Meeting (2017)


Best Poster Award, 8th Life Science Meeting (2a017)


Würdigungspreis des Bundesministeriums für Wissenschaft,

Wirtschaft und Forschung (2017)

Hermann Stuppner, Department of Pharmacognosy:

Wissenschaftspreis für außergewöhnliche Forschungsleistung der

Stiftung Südtiroler Sparkasse, 2017

Hermann Stuppner, Department of Pharmacognosy:

Bruker Award, 2017

Birgit Waldner, Department of General, Inorganic and


Poster award of the Molecular Modeling Workshop Erlangen

Alexander Weiss, Research Department for Biomedical Aging

Research:

Grant D. Swarovski AG, “Struktur- und Aktivitätsbestimmung des

menschlichen Stoffwechselenzyms FAHD2a”

Julia Wunderer, Department of Zoology

Best Poster Award (1st Place), Life Science PhD Meeting Innsbruck 2017

Julia Wunderer, Department of Zoology

Best Short Talk Award (1st Place), 6th Annual CMBI Meeting 2016

Awards and honors for CMBI scientists

CMBI - meetings

CMBI - meetings and seminar series

LIFE SCIENCE PHD MEETING

This meeting was held in the Center for Chemistry and Biomedicine in

Innsbruck on April 18-19, 2017. It brings together the annual meetings

of the different FWF-funded excellence doctoral programs and, most

importantly is organized by PhD students. The participating programs

were MCBO, SPIN, and HOROS but all PhD students of both universities

were invited. The student organizers also brought in excellent plenary

speakers: Catherina Becker (University of Edinburgh, UK), Jörg Köhl

(University of Lübeck, DE) and Arnoud Sonnenberg (The Netherlands

Cancer Institute, Amsterdam, NL). Of course, CMBI many CMBI PhD

students and postdocs alo participated and ppresented their recent re-

search findings. Some of them won prizes, such as Nadine Ornter (Phar-

macology, Pharmacy) for an excellent oral presentation (together with

jury member Prof. Raimund Margreiter).

23RD SCIENTIFIC SYMPOSIUM

OF THE AUSTRIAN PHARMACOLOGICAL SOCIETY APHAR

CMBI members are also part of the Austrian Pharmacological Society

APHAR and were in charge of organizing the annual APHAR meeting in

Innsbruck on September 28–29, 2017. In addition to regulatory aspects

of the European Medicines Agency (plenary lecture by Thomas Salmon-

sen, London & Medicinal Products Agency, Uppsala, SWE) John A. Ci-

dlowski (Natl Inst. of Environmental Health Services, USA) and Michel

Bouvier (Univ. de Montréal, CAN) also presented recent work not only

interesting for pharmacologists but also for the CMBI community.

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Hermann Stuppner

Hermann Stuppner

Michael Schauperl

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CMBI - meetings and seminar seriesCMBI - meetings and seminar series

6TH ANNUAL CMBI MEETING INNSBRUCK 2016

On March 3rd and 4th, the CMBI held its 6th annual joint meeting in

Gnadenwald focusing on drugs and biotechnology, proteomics and me-

tabolomics, protein structure, signaling, disease and stress mechanisms.

About 120 – mostly young – researchers from CMBI member labs gath-

ered in order to share their newest Life Science findings in more than 70

oral and poster presentations and to initiate discussion and interaction.

Three impressive, high-profile plenary speakers, Christian Griesinger

(MPI Göttingen), Remco Sprangers (MPI Tübingen), Almut Schulze (Uni

Würzburg), and an inspiring Introduction Lecture held by the newly ap-

pointed faculty member Frank Edenhofer complemented the program.

As in previous years, three prizes were selected with the help of the

plenary speakers for the best young scientists’ conference presenta-

tions. Two poster prizes were awarded to Marina Frener (Department

for Organic Chemistry) and Armin Wilfinger (Department of Molecular

Biology). The award for the best short talk was given to Julia Wunderer

(Department of Zoology).

9TH ÖGMBT ANNUAL MEETING 2017 &

8TH LIFE SCIENCE MEETING INNSBRUCK

This largest regular life science meeting in western Austria took place

in Innsbruck from September 25–27, 2017. It also serves as a key annual

meeting of the biomedical and biological research community of the

two Innsbruck universities. The CMBI groups also actively participated

with interesting oral and poster presentations thereby increasing the

critical mass of the event. All enjoyed the interdisciplainary conversa-

tions with scientists from all over Austria. Excellent invited speakers also

particpated with the lively discusisons at the posters. Invited speakers

were Andrea Ballabio, TIGEM, IT; Thomas Carell, LMU, DE; Christine Falk,

MHH, DE; Micheala Frye, University of Cambridge, UK; Florian Greten,

FCI, DE; Silvio Gutkind, UCSD, US; Karl Lohner, KFU Graz, AT; Alexander

Mankin, UIC, US; Richard Marais, University of Manchester, UK; Alexan-

der Meissner, Harvard University, US; Maria M. Mota, iMM Lisboa, PT;

Matthias Peter, ETH Zürich, CH; Steven Taylor, University of Manchester,

UK; Andreas Trumpp, DKFZ, DE; Georg Winter, CeMM, AT; Nieng Yan,

Tsinghua University, CN. Students and young scientists from several FWF-

funded excellence consortia participated at this meeting, including the

doctoral programs SPPIN, HOROS and MCBO as well as the neuroscience

research consortium SFB-F44. CMBI investigators actively participate in

all these programs.

102 103 CMBI - meetings and seminar series

External speakers at previous CMBI meetings

In addition to the many exciting short talks and poster presentations from

members of the CMBI and the Biocenter, guest lectures from invited top

scientists contributed to the lively discussions. Like in previous meetings,

the speakers also served as advisory experts for our research activities and

as referees for the poster awards for young scientists.

6th CMBI Meeting Innsbruck, Innsbruck, Tyrol, March 3th - 4th, 2016

>> Christian Griesinger

Max Planck Institute for Biophysical Chemistry Göttingen, Germany

>> Frank Edenhofer, University of Innsbruck, Austria

>> Remco Sprangers, Max Planck Campus Tübingen, Germany

>> Almut Schulze, University of Wuerzburg, Germany

7th Life Science Meeting Innsbruck, Innsbruck, Tyrol, Feb. 27th, 2015

>> Peter Hinterdorfer, University of Linz, Austria

>> Eduard Stefan, University of Innsbruck, Austria

>> Peter Ladurner, University of Innsbruck, Austria

>> Gunter Meister, University of Regensburg, Germany

>> Gerald Obermair, Medical University of Innsbruck, Austria

>> Natascha Kleiter, Medical University of Innsbruck, Austria

>> Pascal Meier, ICR London, UK

>> Marlies Meisl, University of Chicago, USA

>> Martin Puhr, Medical University of Innsbruck, Austria

>> Bill Earnshaw, University of Edinburgh, UK

6th Life Science Meeting Innsbruck, Innsbruck, Tyrol, Sept. 24th - 25th, 2014

>> Robert T. Batey, University of Colorado Boulder, USA

>> Veronika Sexl, University of Veterinary Medicine, Vienna, Austria

>> Florian Kronenberg, Medical University of Innsbruck, Austria

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CMBI - meetings


5th Life Science Meeting Innsbruck, Innsbruck, Tyrol, Sept. 25th - 27th, 2013

>> Asifa Akhtar

Max Planck Institute of Immunobiology and Epigenetics, Germany

>> Michel Desjardins, Universite de Montreal, Canada

>> Carl-Philipp Heisenberg, IST Austria

>> Karolin Luger, Colorado State University, USA

>> Frauke Melchior, ZMBH Heidelberg University, Germany

>> Nikolaus Pfanner, University of Freiburg, Germany

>> Britta Qualmann, Friedrich-Schiller-University Jena, Germany

>> Elena Rugarli, University of Cologne, Germany

>> Susan S. Taylor, University of California San Diego, USA

4th Life Science Meeting Innsbruck, Igls, Tyrol, Sept. 27th - 28th, 2012

>> Christine Foyer

Centre for Plant Sciences, University of Leeds, United Kingdom

>> Ari Helenius, Institute of Biochemistry, ETH Zürich, Switzerland

>> Anne-Claude Gavin

Structural and Computational Biology, EMBL Heidelberg, Germany

3rd Life Science Meeting Innsbruck, Igls, Tyrol, Sept. 23th - 24th, 2011

>> Ilme Schlichting

Department of Biomolecular Mechanisms, Max Planck Institute for Medical

Research, Heidelberg, Germany

>> Adrian R. Ferré-D’Amaré

Laboratory of RNA Biophysics and Cellular Physiology, Biochemistry and

Biophysics Center, National Heart, Lung and Blood Institute, Bethesda, USA

>> Daniel Minor

Cardiovascular Research Institute, Departments of Biochemistry & Biophysics,

and Cellular & Molecular Pharmacology California Institute for Quantitative

Biomedical Research, University of California, San Francisco, USA

2nd Life Science Meeting Innsbruck, Igls, Tyrol, Sept. 24th - 25th, 2010

>> Maria Sibilia

Institute for Cancer Research, Medical University of Vienna, Austria

>> Adriano Aguzzi

Institute of Neuropathology, University Hospital of Zürich, Switzerland

>> Rik Korswagen

Hubrecht Institute, Utrecht, Netherlands

1st Life Science Meeting Innsbruck, Igls, Tyrol, Sept. 18th - 19th, 2009

>> Dirk Trauner

Department of Chemistry and Biochemistry, LMU Munich, Germany

>> Didier Stainier, University of California, San Francisco, USA

>> Wolfgang Baumeister

Max-Planck-Institute of Biochemistry, Martinsried, Germany

104 105

5th Annual CMBI-Meeting Igls, Tyrol, Sept. 26th - 27th, 2008

>> Peter Hegemann

Institute for Biology, Experimental Biophysics, Humboldt University Berlin,

Germany

>> Stefan Schulte-Merker

Hubrecht Laboratory, Netherlands Institute for Developmental Biology

Utrecht, Netherlands

4th Annual CMBI-Meeting Igls, Tyrol, Sept. 28th - 29th, 2007

>> Ulf R. Rapp

Medical Radiation & Cell Research, Univ. of Würzburg, Germany

>> Gregory J. Kaczorowski

Merck Research Laboratories, Rahway, New Jersey, USA

>> Thomas W. Holstein

Institute of Zoology, University of Heidelberg, Germany

3rd Annual CMBI-Meeting Vill, Tyrol, Sept. 29th - 30th, 2006

>> Naweed I. Syed, Anatomy and Physiology, University of Calgary, Canada

>> Erwin F. Wagner

Research Institute of Molecular Pathology, Vienna, Austria

>> Walter Schaffner

Institute of Molecular Biology, University of Zurich, Switzerland

2nd Annual CMBI-Meeting Vill, Tyrol, Sept. 30th - Oct. 1st, 2005

>> Wolfram Saenger

Inst. of Chemistry & Crystallography, Free University Berlin, D

>> Peter Herrlich, Institute of Molecular Biotechnology, Jena, Germany

>> Elisabeth Knust, Institute of Genetics, University of Düsseldorf, Germany

1st Annual CMBI-Meeting Vill, Tyrol, Oct. 1st - 2nd, 2004

>> Robert Huber

Nobel Laureate in Chemistry, MPI of Biochemistry, Martinsried, D

>> Reinhard Fässler

Max-Planck-Institute of Biochemistry, Martinsried, Germany

>> Daniela Pietrobon

Dept. of Biomedical Sciences, University of Padova, Italy

CMBI - seminar seriesCMBI - meetingsCMBI - Meetings and Seminar Series

sem

inar

s | The CMBI seminars are a very important integrative and multidisciplinary ac-

tivity of the CMBI and are also part of the PhD programs established within

the CMBI. So far, it hosted 111 lectures from renowned scientists from the US,

Canada, Australia, Sweden, Denmark, France, Italy, UK, Ireland, Netherlands,

Germany, Belgium, Switzerland, and Austria. It also provides a forum for ex-

cellent scientists from the Innsbruck Universities. Seminar speakers of the last

three years are listed here:

2017Rasmus Linser, Ph.D.

Department for Chemistry, Ludwig-Maximilians-University of Munich,

Germany

Michel Bouvier, Ph.D.

F.C.A.H.S., FRSC Université de Montréal, Institute of Research in

Immunology and Cancer, Montréal, Canada

Oliver Rocks, Ph.D.

Max Delbrück Center for Molecular Medicine, Berlin, Germany

David Gillespie, Ph.D.

Institute of Biomedical Technologies, Centre for Biomedical Research

of the Canary Islands

Nathan Lüdtke, Ph.D.

University of Zurich, Department of Chemistry, Zurich, Switzerland

David Henshall, Ph.D.

Professor of Molecular Physiology and Neuroscience, Royal College of

Surgeons in Ireland, Dublin, Ireland

Helmut Schwarz, Ph.D.

Institute of Chemistry, Technical University of Berlin, Germany

Hans Schöler, Ph.D.

Max-Planck Institute for Molecular Biomedicine, Münster, Germany

Andrea Pauli, Ph.D.

IMP - Research Institute of Molecular Pathology, Vienna, Austria

Monika Hassel, Ph.D.

Morphology and Evolution of Invertebrates, Philipps-University of

Marburg, Germany

2016Stephan A. Sieber, Ph.D.

Department of Chemistry, Technical University of Munich, Germany

Dirk Trauner, Ph.D.

Department for Chemistry and Biochemistry, Ludwig-Maximilians-

University of Munich, Germany

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CMBI - meetings and seminar seriesCMBI - meetings and seminar series

106

CMBI - seminar series


Jeffrey Liu, Ph.D.

Max Planck Institute of Biochemistry, Martinsried, Germany

Alois Fürstner , Ph.D.

Organometallic Chemistry, Max-Planck-Institute, Mühlheim, Germany

Dominique Massotte, Ph.D.

Institut des Neurosciences Cellulaires et Intégratives, Strasbourg,

France

Michael Heise, Ph.D.

South Westphalia University of Applied Sciences, Iserlohn, Germany

Norbert Bischofberger, Ph.D.

Gilead Sciences, California, USA

Gerald Schwank, Ph.D.

Institute for Molecular Health Sciences, ETH Zurich, Switzerland

Rudi Vennekens, Ph.D.

Laboratory of Ion Channel Research Biology, KU Leuven, NL

Frank Edenhofer, Ph.D.

Institute of Molecular Biology, University of Innsbruck, A

Jutta Schüller, Ph.D.

Taconic Biosciences, Cologne, G

Roland Sigel, Ph.D.

Department of Chemistry, University of Zurich, CH

2015Stefan Hörtensteiner, Ph.D.

Institute of Plant Biology, University of Zurich, CH

Georg S. Baillie, Ph.D.

Molecular Pharmacology, Institute of Cardiovascular and Medical

Sciences, University of Glasgow, UK

Daniel Gerlich, Ph.D.

IMP, Vienna, AT

Elena Conti, Ph.D.

Director, MPI, Munich, Germany

Alexander Stark, Ph.D.

IMP, Vienna, AT

Markus Ralser, Ph.D.

CSBC, University of Cambridge, UK

Matthias Hentze, MD

EMBL, Heidelberg, Germany

Roger Schibli, Ph.D.

Institute for Pharmaceutical Sciences, ETH Zurich, Switzerland

sem

inar

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Centrum für

Molekulare Biowissenschaften Innsbruck

Universität Innsbruck

Office: Innrain 80-82a

A-6020 Innsbruck

Tel: +43 512 507-57501

Fax: +43 512 507-57599

[email protected]

www.uibk.ac.at/cmbi

contact |

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