Download - Scilifelab stockholm 2012
Annual report 2012Science for Life Laboratory Stockholm
2 | 2012 Annual report SciLifeLab Stockholm
SciLifeLab Stockholm Annual report 2012 | 1
Science for Life Laboratory Stockholm
Annual report 2012
Acini of the mammary gland of normal human breast with OmniFluorBright (OFB) staining.
SciLifeLab Stockholm Annual report 2012 | 3
Pho
to: P
rof.
Las
zlo
Sze
kely
, KI
SciLifeLab in brief
SciLifeLab’s vision is to be an internationally leading center in large-scale life science research. With the motto Health and Environment the research supported and performed is spanning a broad field, aiming not only for deeper knowledge about human diseases, improved health care, development of diagnostic tools and potential drugs, but also for mapping of microbial activities in sensitive ecosys-tems, engineering for biofuel production and plant biotechnology.
SciLifeLab develops and provides access to ad-vanced instrumentation and technical expertise in large-scale molecular biosciences. The objective is to enable Swedish researchers to carry out extensive and comprehensive analysis of genes, transcripts and proteins in humans, plants and relevant microbes, such as viruses and bacteria, and to cast light on the complex interplay between different
molecular components in living cells, tissues and organs related to human diseases or environmental issues. In order to interpret the massive amount of data produced in many large-scale analyses, expertise in bioinformatics and systems biology is essential and prioritized areas at SciLifeLab.
By combining a “tool box” of advanced instrumen-tation and expertise from a wide range of life science areas, interdisciplinary research involving high-throughput DNA sequencing, analysis of gene expression, protein profiling, cellular profiling, advanced bioinformatics, biostatistics and systems biology, is carried out.
The two nodes in Stockholm and Uppsala will in the middle of 2013 merge into one organization. This report describes the activities of SciLifeLab Stockholm during 2012.
Over the past three years, Science for Life Laboratory (SciLifeLab) has been built up
in Stockholm and Uppsala to serve as a national infrastructure for high-throughput
and technically advanced research in the life sciences, and to provide an attractive
research environment for top-level research groups. SciLifeLab was established in
2010, with support from the Swedish government. It is a collaboration between the
Royal Institute of Technology (KTH), Karolinska Institutet (KI), Stockholm University
(SU) and Uppsala University (UU).
4 | 2012 Annual report SciLifeLab Stockholm
Table of contents
SciLifeLab in brief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
SciLifeLab Stockholm 2012 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Highlights of 2012 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
SciLifeLab in constant progress . . . . . . . . . . . . . . . . . . . . . . . . 8
The organization of SciLifeLab Stockholm 2012 . . . . . . . . . . 9
The platforms offer technology infrastructure
and competence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Highlights from research
The Subcellular Protein Atlas . . . . . . . . . . . . . . . . . . . . . . . . . 13
Targeting DNA repair to find novel
anti-cancer treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Membrane protein biogenesis . . . . . . . . . . . . . . . . . . . . . . . . 15
Reading the genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Na,K-ATPase – an overlooked protein in the brain . . . . . . . 17
Spatial transcriptomics of the brain . . . . . . . . . . . . . . . . . . . . 18
Understanding the molecular basis
of nerve signals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Bioinformatics for network and systems biology . . . . . . . . 22
Collaboration with industry . . . . . . . . . . . . . . . . . . . . . . . . . . 23
The SciLifeLab Stockholm researchers . . . . . . . . . . . . . . . . . 24
SciLifeLab Stockholm – Scientific publications . . . . . . . . . . . 26
The Platform Facilities
Genomics Experimental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Genomics Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Cell Profiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Biobank Profiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Cell Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Advanced Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Clinical Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Tissue Profiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Chemical Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Protein Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Advanced Light Microscopy (ALM) . . . . . . . . . . . . . . . . . . . . 41
Karolinska High Throughput Center (KHTC) . . . . . . . . . . . . 42
Bioinformatics Infrastructure for Life Sciences (BILS) . . . . . 43
The Wallenberg Advanced Bioinformatics
Infrastructure (WABI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Management of SciLifeLab Stockholm . . . . . . . . . . . . . . . . . 46
SciLifeLab Stockholm Annual report 2012 | 5
SciLifeLab Stockholm 2012
The development of SciLifeLab Stockholm has continued at a rapid pace during 2012 and the year has been scientifically productive. The center has noticed an increased interest from researchers to use the state-of-the-art technologies provided by the platform facilities. Hundreds of collaborative and service projects have been completed with users from all major universities in Sweden. To further broaden the resources available, three new platform facilities have been established. The center has also expanded with an additional 170 researchers, reaching 350 persons at the end of 2012. These include almost 40 senior research leaders performing research in a wide range of molecular bioscience areas. SciLifeLab Stockholm will continue to expand during 2013 when an adjacent building will be inaugurated, then encompassing more than 600 researchers and 14,000m2 of space for the technical infrastructure and research within large-scale life science.
Substantial external funding has enabled investments in new instrumentation and recruitment of personnel to several platform facilities. Through generous grants from the Knut and Alice Wallenberg Founda-tion the Genomics facility has been able to triple the sequence capacity during the year and an infrastruc-ture for in-depth bioinformatics support has been established. This kind of support is an important key for success in on-going large-scale studies.
The strengthened research environment is illustrated by the considerable increase in number of publica-tions produced by SciLifeLab Stockholm researchers over the year. During 2012 one article per week has been published in high impact journals such as Nature, Science and PNAS. Read more about some of the research highlights at SciLifeLab Stockholm on page 12 to 22. Several patents have also been filed, and there are lively collaborations with industry on different levels.
In 2012, the Swedish government decided on addi-tional funding to SciLifeLab, with the mission to unify the Stockholm and Uppsala nodes and become an infrastructure with a national responsibility. SciLifeLab will provide large-scale state-of-the-art instrumentation and technical know-how, including in-depth bioinformatics support, to all Swedish researchers in order to strengthen multidisciplinary research throughout the nation.
The year of 2012 has been an exciting and
rewarding year for SciLifeLab Stockholm.
Development of SciLifeLab Stockholm from the start in 2010. The center has expanded with new Platform Facilities and research groups each year. In 2013 the nodes in Stockholm and Uppsala will merge into one organization and become a national infrastructure for large-scale biosciences.
6 | 2012 Annual report SciLifeLab Stockholm
• Several new bioinformatics algorithms were developed
and published, including FunCoup 2 .0 and BOCTOPUS
• Novel methods for quantitative proteomics using mass
spectrometry were developed
• A step towards more efficient spruce breeding programs
was taken by using the next generation sequencing
facility at SciLifeLab coupled with advanced bioinformatics
and molecular biology methods
• Dramatic resistance to colorectal cancer formation was
confirmed in mouse models
• An additional 4000 m2 of space was inaugurated and
another 170 researchers moved in to reach a total of 350
persons
For details regarding some of the scientific highlights, please go to pages 12 to 22.
• The Swedish government announced increased funding to
SciLifeLab and the start of a new organization in 2013
• The Knut and Alice Wallenberg Foundation awarded
grants to strengthen the Genomics facility and to start up
the Wallenberg Advanced Bioinformatics Infrastructure
(WABI)
• Three new platform facilities were established; Advanced
proteomics, Chemical biology and Protein production
• AstraZeneca started up the Translational Science Centre
at SciLifeLab Stockholm and announced a first round of
funding for research projects
• The Human Protein Atlas announced in September 2012
the mapping of 70% of the human protein-coding genes
• Three SciLifeLab Stockholm researchers were awarded 53
MSEK from the Knut and Alice Wallenberg Foundation for
research about viruses and bacteria, the brain and its
diseases and for understanding and developing new
cancer drugs . Two of its Center Directors (von Heijne and
Uhlen) received Wallenberg Scholar Awards
Highlights of 2012
Pho
to: H
åkan
Lin
dg
ren
Here follows some examples of organizational
and scientific highlights during the year.
8 | 2012 Annual report SciLifeLab Stockholm
SciLifeLab in constant progress
From 2013 SciLifeLab will receive substantially increased funding from the Swedish government and become a national infrastructure for large-scale bioscience. A new organization will start in the middle of 2013 when the two nodes in Stockholm and Uppsala will merge into one organization with a common board.
SciLifeLab’s vision to take part in strengthening health care, through new technologies and products, has resulted in the start up of two new areas in the center. The first one is a platform for Drug Develop-ment that will bring activities already ongoing, such as small molecule library and RNAi cell screening, under one roof and expand and complement these activities with expertise in drug development. Second, to further strengthen the collaboration and integration with the health care sector, SciLifeLab Stockholm will expand its activities with a clinical genomics facility to perform next generation sequenc-ing on patient samples with fast processing time.
During 2013 SciLifeLab Stockholm will grow with approximately 30 new research groups, encompass-ing more than 600 persons at the end of the year.
The aim is also to accommodate national and international research groups with strategically important expertise to join SciLifeLab. Fellowships will allow young research leaders to work in the interdisciplinary environment of SciLifeLab for a shorter or longer period and contribute to an even more dynamic research environment.
The links to other Swedish universities will be further strengthened during the years to come, as SciLifeLab will have a national responsibility to provide access to advanced technologies and exper-tise in bioscience. Several areas of expertise in life science at other universities will also be formally linked to SciLifeLab. The National Reference Committee, with representatives from all major Swedish universities, will continue to give strategic advice on the development of SciLifeLab and monitor the accessibility and output from the platform facilities. In order to provide access to technologies and expertise and to support knowledge exchange and the spread of new technologies, space for guests has been made available both in offices and laboratories and a program of courses, workshops and seminars will be provided.
SciLifeLab aims to be an internationally leading center for providing
and developing state-of-the-art technology and expertise in large-scale
molecular biosciences and to produce first-class interdisciplinary research.
SciLifeLab Stockholm Annual report 2012 | 9
The organization of SciLifeLab Stockholm 2012
SciLifeLab Stockholm is a collaboration between the Royal Institute of Technology (KTH), Karolinska Institutet (KI) and Stockholm University (SU). The SciLifeLab Board has the responsibility for decisions regarding the budget and strategic development of the center. The board consists of six members, two from each university. An international Scientific Advisory Board and the National Reference Committee give advice to the board.
In the end of 2012, a new operative management structure at SciLifeLab Stockholm was introduced comprising three Center Directors and three Scientific Directors, each representing one of the universities. The Center Directors are responsible for implementing the board’s decisions about the center budget and activities. Moreover, a Site Director is responsible for the day-to-day operations.
The center included seven platforms during 2012 and a number of platform facilities. The platforms represent areas of research where a combination of technologies
is generally used. The platform facilities are units each representing a certain technology and which can offer services to internal and external research groups. A number of senior researchers are appointed as Platform Directors with responsibility for the scientific develop-ment of the platforms. The day-to-day activities of the platform facilities are headed by Facility Managers.
The Affiliated Faculty of SciLifeLab Stockholm is a network of representatives from all departments, research centers and other organizations in the Stockholm region with an interest in the activities at SciLifeLab Stockholm.
In order to coordinate activities between the Stockholm and Uppsala node and plan for a common organization in 2013 a coordination committee was initiated in 2012. This committee consists of one representative from each of the four universities (KTH, SU, KI and UU).
The research leaders of SciLifeLab Stockholm are presented on page 24–25. More information about the Platform facilities and the services available can be found on page 10 and 28–45 and at www.scilifelab.se.
Fredrik Sterky Assoc. Prof. Site Director
Martina Selander Personnel and administration
Mikaela Friedman Dr., Scientific communication and External relations
Mathias Uhlén Prof. (KTH)Center Director
Gunnar von Heijne Prof. (SU)Vice Center Director
Jan Andersson Prof. (KI)Vice Center Director
Pho
to: U
lf S
irb
orn
10 | 2012 Annual report SciLifeLab Stockholm
The Genomics platform is the most established platform and carried out several hundreds of research projects during 2012. It offers massively parallel DNA sequencing and bioinformatics support for projects in plants, humans, microorganisms and cell lines. With the latest instrumentation, an entire human genome can be sequenced in 27 hours. During 2013, the new technology and expertise will enable a new facility “Clinical genomics” to emerge. Next generation sequencing on patient samples will be performed in collaboration with the treating physicians and hospital geneticists.
The MS proteomics platform as well as the Function-al biology and Bioimaging platforms are also carry-ing out large numbers of projects. Other platforms, such as Affinity proteomics and Functional genomics require more detailed experimental planning and are customized for each user. In many cases, SciLifeLab Stockholm can provide unique competence and resources. One example is the Affinity Proteomics platform that uses the unique resource of affinity reagents from the Human Protein Atlas (HPA) project allowing high-throughput biomarker discov-ery screening in large cohorts of clinical samples. This platform also provides means to validate antibodies and/or cell lines in a subcellular fashion using the HPA reagents and confocal microscopy.
The Platform facilities are presented in more detail on page 28 to 45.More information about the Platform facilities is available at www.scilifelab.se.
SciLifeLab has competences in a wide range of areas that are organized in platforms, which offer state-of-the-art technologies and expertise to the research community. During 2012 the center included seven platforms; Genomics, Affinity Proteomics, Mass Spectrometry (MS) Proteomics, Functional Biology, Bioimaging, Functional Genomics and Bioinformat-ics & Systems Biology. The platforms are divided into smaller units, platform facilities that handle one or a few different technologies within the field.
Each platform facility is headed by a facility manager with responsibility for the daily work, personnel and budget. The strategic development and overall budget for the platform is managed by a platform director. In several cases, the platform facilities in Stockholm are jointly run with a similar facility at the Uppsala node. This allows efficient handling of large numbers of projects and samples. In other areas, the technologies and expertise are unique to each site.
During 2012, the number of projects carried out in the facilities has increased considerably with users from all Swedish universities. The projects cover a broad range of molecular bioscience research and considerable parts of the research being performed is focusing on an increased molecular level/mechanis-tic understanding of human diseases, plants, and microbes, finding new biomarkers for disease and development of new treatments.
The platforms offer technology infrastructure and competence
Pho
to: D
r. J
an M
uld
er, K
I
SciLifeLab Stockholm Annual report 2012 | 11
Section of a mouse olfactory bulb. Amphiphysin is a protein associated with the cytoplasmic surface of synaptic vesicles. Autoantibodies against this protein have been associated with stiff-man syndrome. Antibodies against amphiphysin (green) stain many neurons in the mouse brain including the olfactory bulb.
12 | 2012 Annual report SciLifeLab Stockholm
Immunofluorescent staining of human MCF-7 metastatic breast adenocarcinoma cells, using an antibody HPA049798 towards Zinc finger CCCH domain-containing protein 14, shows positivity in nucleus but not nucleoli.
SciLifeLab Stockholm Annual report 2012 | 13
Highlights from research
All cells of higher organisms such as humans or animals
are organized into compartments with specialized
functions. These so called organelles are defined by
their own chemical characteristics and molecular
composition. For example an organelle called mito-
chondrion has the function to provide energy for the
cell, whereas the cytoskeleton serves to maintain
cellular shape, movement and functions as a railroad
for intracellular transport. Thus, knowing the exact
subcellular location of a given protein is of great
importance as it indicates the protein function and
leads to a better understanding of how and why
proteins interact in networks and signaling pathways.
Ever since the human genome was first characterized much efforts has been put into the identification and characterization of the gene products – the proteins. A key to unlock a more complete understanding of the information embedded in the human genome and the complex machinery of living cells is to know the subcellular localization for every protein. As part of the Human Protein Atlas project our research is therefore focused on determining the subcellular localization of all human proteins by the use of specific antibodies and high-resolution microscopy.
During 2012, the Subcellular Protein Atlas program at SciLifeLab Stockholm has expanded in different directions, as reported in several publications. The panel of human cells has increased to fifteen cell lines of different origin from which the most suitable is
selected based on gene transcript expression levels (1). Furthermore, a pipeline for validation of antibody binding and protein subcellular location using siRNA (2) and automated classification of staining patterns (3) has been developed. Beyond this, we have demonstrated the added value of using a complementary technique such as live cell imaging of tagged proteins to allow a complete investigation of the subcellular human proteome (4).
Currently, the Subcellular Protein Atlas contains ~100,000 images corresponding to the localization of over 12,000 proteins. The aim of the presented atlas is to make subcellular information for all human proteins publicly available, with the ultimate aim to facilitate functional studies of proteins.
References1. Danielsson, F. et al (2013) “RNA Deep Sequencing as a Tool for
Selection of Cell Lines for Systematic Subcellular Localization of All Human Proteins” J Proteome Res. 12 (1): 299-307.
2. Stadler, C. et al (2012) “Systematic validation of antibody binding and protein subcellular localization using siRNA and confocal microscopy” J Proteomics 75 (7): 2236-51.
3. Li, J. et al (2012) “Estimating Microtubule Distributions from 2D Immunofluorescence Microscopy Images Reveals Differences among Human Cultured Cell Lines” PLoS One. 7 (11): e50292.
4. Stadler, C. et al (2013) “Immunofluorescence and fluorescent- protein tagging show high correlation for protein localization in mammalian cells” Nat Methods, in press.
Contact
Emma Lundberg
E-mail: [email protected]
The Subcellular Protein Atlas
Pho
to: M
arti
n H
jelm
are,
KTH
14 | 2012 Annual report SciLifeLab Stockholm
Highlights from research
Cancers are characterized by genetic mutations and an
overall high load of DNA damage, which can be
exploited for novel therapies. Our laboratory focuses
on a multidisciplinary approach to understand basic
properties of DNA repair at a molecular level, and
identify and validate novel protein targets within the
DNA repair pathway (1, 2). Using an open innovation
approach, in close collaboration with academic groups
and clinicians, we develop small molecule inhibitors to
novel targets that are tested in early proof of concept
trials in patients.
Cancer remains the most common cause of death for individuals aged below 80 in industrialized countries and novel more effective treatments for cancer are urgently needed. Traditional radio- and chemo-therapy work by causing an unbearable load of DNA damage in cancer cells, which effectively eradicate the cancer, but also cause harmful side effects. Our aim is to selectively introduce DNA damage in tumors without harming non-malignant cells. We previously demonstrated that cancers caused by mutations in BRCA1 or BRCA2 genes rely on PARP for survival and that PARP inhibitors can selectively kill off the cancers (3). This is now tested in numerous clinical trials. Based on this new concept of synthetic lethality, we are identifying genes that are required for survival only in the mutated cancer cells.
One characteristic of most cancers is a high level of oxidative damage, which helps in generating mutations
required for cancer development. However, to avoid lethal DNA damage cancer cells appear dependent on new proteins to survive; such as nucleotide hydrolases. By specifically targeting nucleotide hydrolases we have identified a new strategy to attack cancer. We have developed small molecule inhibitors against these proteins, which kill cancer cells without harming normal growing cells. Our most effective inhibitors will be further optimized, tested in in vivo tumor models and passed on to clinical trials with the aim of treating cancer patients.
By working in a multidisciplinary fashion we are able to combine expertise from several disciplines such as biochemistry, medicinal chemistry, molecular biology, clinical oncology and pharmacology. In addition, we are fortunate to have a number of collaborations, both national and international, across a range of disciplines to complement our in-house expertise.
References1. Groth, P. et al (2012) “Homologous recombination repairs
secondary replication induced DNA double-strand breaks after ionizing radiation” Nucleic Acids Res. 40 (14): 6585-94.
2. Elvers, I. et al (2012) “CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation” Nucleic Acids Res. 40 (17): 8440-8.
3. Bryant, H.E. et al (2005) “Specific killing of BRCA2-deficient tumors with inhibitors of poly(ADP-ribose)polymerase” Nature, 434 (7035): 913-7.
Contact
Thomas Helleday
E-mail: [email protected]
Targeting DNA repair to find novel anti-cancer treatments
SciLifeLab Stockholm Annual report 2012 | 15
Highlights from research
All cells are surrounded by a lipid membrane that
separates them from the outside world and protect
their content. Cell membranes are stuffed full of
proteins. Membrane proteins are central players in all
types of cells, from bacteria to man. They make it
possible for cells to take up nutrients from the environ-
ment, to excrete waste products, and to receive and
transmit various kinds of signals from other cells. Being
the gatekeepers of the cell, membrane proteins are also
favorite drug targets; it is estimated that more than half
of all drugs currently on the market bind to and change
the activity of membrane proteins.
Much effort is currently spent across the world to determine high-resolution structures of membrane proteins in order to understand their function on the molecular level. But in order to fully understand membrane proteins, structures are not enough. We also need to figure out how membrane proteins are manu-factured in the cell, how they are inserted into the membrane, and how they fold into the final structure. This is important not only from a basic science perspec-tive, but also to understand how mutations in medically important membrane proteins can cause proteins to misfold and thereby destroy their function.
Our research is focused on these early stages in the life of membrane proteins. In particular, we have recently been able to discover some “tricks” that nature has invented in order to make membrane proteins with membrane-embedded parts that by themselves cannot
enter a membrane (1). This has been a conundrum, but we now understand the basic principles. Another advance is the development of a new method that allows us to measure forces acting on membrane proteins during their insertion into the membrane (2). This has not been possible before, and opens up a new window for probing the molecular mechanisms that underlie membrane protein folding in the cell. References1. Öjemalm, K. et al (2012) “Orientational preferences of neighboring
helices can drive ER insertion of a marginally hydrophobic transmembrane helix” Molecular Cell 45 (4): 529-40.
2. 1Ismail, N. et al (2012) “A bi-phasic pulling force acts on transmem-brane helices during translocon-mediated membrane integration” Nature Structural and Molecular Biology 19 (10): 1018-22.
1Editor’s Choice, Science 19 October 2012
Contact
Gunnar von Heijne
E-mail: [email protected]
Membrane protein biogenesisTargeting DNA repair to find novel anti-cancer treatments
A typical membrane protein. This particular protein, called EmrE, helps bacteria extrude toxic compounds such as antibiotics through their membrane.
16 | 2012 Annual report SciLifeLab Stockholm
Highlights from research
After the human genome was sequenced in 2000, it was
hoped that the knowledge of the entire sequence of
human DNA could rapidly be translated to medical benefits
such as novel drugs, and predictive tools that would
identify individuals at risk of disease. However, this turned
out to be harder than expected, one of the reasons being
that only the 1% of the genome that codes for proteins
could be read. The remaining 99% contains information
about when and where these proteins are made, and is to
us like a book written in a foreign language – we know the
letters but cannot understand why a human genome
makes a human or the mouse genome a mouse. Why some
individuals have higher risk to develop common diseases
such as heart disease or cancer is even less well understood.
The Taipale group addresses this problem by studying the
human proteins that read the gene regulatory code:
transcription factors (TFs).
The human genome encodes approximately 1000 TFs, and they bind specifically to short 5 to 20 base pair sequences of DNA, and control production of other proteins. Through the use of a highly automated laboratory, we have identified DNA sequences that bind to over 400 such proteins, representing approximately half of all human TFs. We have also developed compu-tational tools that can use such information to identify gene variants that are linked to disease. We have analysed one particular single nucleotide variant in a region associated with increased risk for developing colorectal and prostate cancers. Although
this variant increases cancer risk only by 20 per cent, it is very common and therefore accounts for more inherited cancer than any other currently known genetic variant or mutation. We removed the gene region containing the risk variant from the mouse genome and found that as a result the mice were healthy, but displayed a small decrease in the expres-sion of a nearby cancer gene, called MYC. However, when these mice were tested for the ability to form tumors after activation of an oncogenic signal that causes colorectal cancer in humans, they showed dramatic resistance to tumor formation. The removed gene region thus appears to act as an important gene switch promoting cancer, and without it tumors develop much more rarely. This study highlights that growth of normal cells and cancer cells is driven by different gene switches, suggesting that further work to find ways to control the activity of such disease-specific switches could lead to novel, highly specific approaches for therapeutic intervention.
References1. Kivioja, T. et al (2012) “Counting absolute number of molecules
using unique molecular identifiers” Nature Methods 9 (1): 72-4.2. Sur, I. et al (2012) “Mice Lacking a Myc Enhancer Element that
Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors” Science 338 (6112): 1360-3.
3. Jolma, A. et al (2013) “DNA-binding specificities of human transcription factors” Cell 152: 327-39.
Contact
Jussi Taipale
E-mail: [email protected]
Reading the Genome
SciLifeLab Stockholm Annual report 2012 | 17
Highlights from research
The sodium pump is a very important protein in the
mammalian cell. While pumping sodium and potassium
ions it consumes 30% of all energy in the body and 60%
of the energy in the brain. Surprisingly, the full picture
of how this protein functions in the human brain is not
clear. Researchers at SciLifeLab are studying the sodium
pump in neurons to understand its role in health and
disease. How it is regulated to preserve energy. How it
acts as a signaling protein. How identified disease
mutations influence its function.
Recent studies have shown that the sodium pump, Na,K-ATPase, not only pumps ions but also has an important role as a signal transducer (1). We have shown that binding of cardiotonic steroids to Na,K-ATPase trigger frequency modulated Ca2+ oscilla-tions with downstream anti-apoptotic effects.
The functional significance of neuronal expression of two different isoforms of Na,K-ATPase, a1 and a3, has been studied by intracellular Na+ imaging. The a3 isoform, which has a higher Na+ affinity than a1, was identified to have a specific role in restoration of intracellular Na+ after the transient influx that occurs during synaptic activity (2).
Applying super resolution microscopy (STED, PALM, SIM) we revealed for the first time the discrete localization of the neuron specific a3 isoform to the neck of dendritic spines (3) and also the spatial interrelationship to dopamine D1R receptors (4).
Super localization microscopy of quantum dot labeled Na,K-ATPase showed that mobility and temporal confinements of the sodium pump in the plasma membrane is a key component for the energy efficient regulation of Na+.
References1. Li, J. et al (2010) “Ouabain protects against adverse developmental
programming of the kidney” Nature Communications, 1: 42.2. Azarias, G. et al (2013) “A specific and essential role for Na,K-
ATPase a3 in neurons co-expressing a1 and a3” J Biol Chem. 288 (4): 2734-43.
3. Blom, H. et al (2011) “Spatial distribution of Na+-K+-ATPase in dendritic spines dissected by nanoscale superresolution STED microscopy” Bmc Neuroscience 12:16.
4. Blom, H. et al (2012) “Nearest neighbor analysis of dopamine D1 receptors and Na(+) -K(+) -ATPases in dendritic spines dissected by STED microscopy” Microsc Rese Tech. 75 (2): 220-8.
Contact
Hjalmar Brismar
E-mail: [email protected]
Na,K-ATPase – an overlooked protein in the brain
Na,K-ATPase a3 is enriched in dendritic spines in hippocampal neurons. Super resolution microscopy of Na,K-ATPase a3 in dendritic spines of a hippocampal neuron. Lower panel show an overlaid confocal micrograph of PSD95 (red) on the super resolution image (grey).
18 | 2012 Annual report SciLifeLab Stockholm
Highlights from research
The human body comprises over 100 trillion cells and is
organized into more than 200 different organs and
tissues. The development and organization of complex
organs, such as the brain, are far from understood and
there is a need to dissect the expression of genes using
quantitative methods. The organs are in themselves a
mixture of differentiated cells to enable all body
functions such as nutrient transport, defense etc.
Consequently, cell function is context dependent, and
the context provided by tissue structure is being
disentangled at the transcriptional level within the
spatial transcriptomics project.
The new advances in high-throughput genomics have reshaped the biological research landscape and in addition to complete characterization of genomes we are also able to study the full tran-scriptome in a digital and quantitative fashion. The bioinformatics tools to visualize and integrate these comprehensive sets of data have also been significantly improved during recent years. Findings by deep RNA sequencing have demon-strated that a majority of the human genes are active in a cell and that a large fraction (75%) of the human protein-coding genes are expressed in most tissues. The transcriptional machinery can therefore be described to be promiscuous at a global level but remains dynamically complex, demonstrated by burst transcription, where brief pulses of transcription are separated by periods of transcriptional silence.
We have recently devised a simple strategy that enables global gene expression analysis in histological tissue sections, yielding transcriptomic information with two-dimensional spatial resolution. This enables the identification of individual transcriptomes of single cells while maintaining the positional information of those cells in the tissue. The RNA sequencing data is visual-ized in the computer together with the tissue section, for instance to display the expression pattern of a gene of interest across the tissue. It is also easy to mark different areas of the tissue section on the computer screen and obtain information on differentially expressed genes between any selected areas of interest.
We are currently creating spatial transcriptional maps of the brain, arguably the most complex organ in the body, with at least hundreds of different distinct neuronal subtypes that are interconnected in precise patterns. Our aim is to improve understanding of neurological and psychiatric diseases, as our current knowledge is still limited, contributing to the difficulty in developing therapies for many of these diseases. Psychiatric and neurological diseases cause much suffering of affected patients and their families and enormous costs to society.
ReferencesPatent PCT/EP2012/056823
Contact
Joakim Lundeberg
E-mail: [email protected]
Spatial transcriptomics of the brain
SciLifeLab Stockholm Annual report 2012 | 19
Data analysis. The data from the spatial transcriptomics experiment is visualized in the spatial transcriptomics viewer software. Virtual analysis of the tissue section is enabled and the user can select and analyze the gene expression in a cell or an area of interest. The user can also look at differential expression between selected regions, or perform an automated virtual analysis for identification of cell types based on predefined expression profiles.
20 | 2012 Annual report SciLifeLab Stockholm
Highlights from research
Ion channels that open and close in response to
electrical signals are membrane proteins that constitute
the fundamental building blocks responsible for e.g.
our nerve signaling and heartbeats. These channels
sense differences in voltage across a cellular membrane
with four special voltage sensor parts (domains) whose
structure changes. It has previously not been possible to
determine how these changes occur. During the last
year, we were able to solve this problem with a new
combination of experiments, bioinformatics and
simulations, which now enables us to track a complete
cycle of a voltage sensor activation in response to
voltage in full atomic detail.
Since it is difficult or impossible to determine a crystal structure with a voltage applied, the only structures available this far have corresponded to the open state of the Kv1.2-2.1 potassium channel. However, in collaboration with Linköping University we have been able to design electrophysiology experiments that capture information from interme-diate states only visited briefly during channel opening or closing. This provides a wealth of new indirect structural information, and in combination with molecular modeling and molecular simulation it enabled us to predict a range of five different atomic-detail models corresponding to states ranging from fully activated to resting voltage-sensor domains (1). This results in a virtual movie of the complete cycle of structural changes of the ion channel, and makes it possible to explain how the gating occurs. For each
intermediate stage, one more charge in a specific part of the protein is moved across a hydrophobic region in the core of the ion channel, which effectively moves it from one side of the membrane to the other (2). We have also been able to use combined experiments and simulations to show that a specific residue (F233) in this region is responsible for making the closing process of potassium channels very slow (3). This likely explains a key property of our nerve system, where all nerve impulses are created by fast (sodium) channels first opening to depolarize the membrane, followed by the slower potassium channel opening to restore the equilibrium – if the latter closed instantly the nerve system would not work.
References1. Henrion, U. et al (2012) “Tracking a complete voltage-sensor cycle
with metal-ion bridges” Proc. Natl. Acad. Sci. 109 (22): 8552-57.2. Lindahl, E. (2012) “Unraveling the strokes of ion channel molecular
machines in computers” Proc. Natl. Acad. Sci. 109 (52): 21186-87.3. Schwaiger, C.S. et al (2012) “The conserved phenylalanine in the
k(+) channel voltage-sensor domain creates a barrier with unidirectional effects” Biophys J. 104: 75-84.
Contact
Erik Lindahl
E-mail: [email protected]
Understanding the molecular basis of nerve signalsTracking the activation cycle of a voltage-gated ion channel
SciLifeLab Stockholm Annual report 2012 | 21
Deactivation of voltage sensor from a voltage-gated ion channel. As the voltage changes, the sensor moves through intermediate states to a resting state where it will push on the pore domain (not shown) to close the channel.
22 | 2012 Annual report SciLifeLab Stockholm
Highlights from research
As more and more high-throughput biological data is
generated, there is a growing need to understand how
genes and proteins are organized in networks. We have
developed a bioinformatics framework for mapping
diverse types of data into a single network of functional
couplings. Such network maps are a tremendous
resource for identifying the functional partners of
genes and proteins, and to analyze relations between
groups of genes. To this end, we have developed
bioinformatics tools to assess the statistical significance
of network crosstalk between gene groups. We are also
elucidating gene regulatory networks by perturbation
experiments and improved bioinformatics methodology.
Network biolog y. FunCoup is a data integration project for producing global comprehensive gene/protein networks of functional couplings. Release 2.0 was built using 9 different types of high-throughput data from 11 different species (1). FunCoup achieves its high coverage by orthology-based transfer of functional coupling between species. The FunCoup website http://FunCoup.sbc.su.se provides unique facilities for analyzing network context of query genes and the conservation of subnetworks in multiple species.
Functional analysis. The FunCoup networks can be used for pathway annotation of gene lists using ”Network Crosstalk Enrichment Analysis”. This measures enrichment of network crosstalk between an experi-mentally derived gene list and known pathways. We have shown that this approach yields
a 5-fold increase in sensitivity compared to tradition-al gene enrichment analysis, which does not use a network (2). Moreover, we have developed an efficient and highly accurate bioinformatics method that improves gene list analysis by clustering the genes into distinct functional groups (3).
Systems biolog y. Dynamic transcriptional gene regulatory networks can be inferred by perturbing some genes, e.g. with RNA interference, and measur-ing the effect this has on other genes. Several model-ing techniques exist for such inferences, but a major problem has been estimating the sparsity of the network, leading to very poor accuracy. To resolve this, we have developed a method that, given suffi-ciently informative data, predicts the optimal sparsity and produces correct regulatory networks (4). Together with SciLifeLab facilities, we are elucidat-ing gene regulatory networks relevant to cancer.
References1. Andrey, A. et al (2012) “Comparative interactomics with Funcoup
2.0” Nucleic Acids Research 40: D821-D828.2. McCormack, T. et al (2013) “Statistical Assessment of Crosstalk
Enrichment between Gene Groups in Biological Networks” PLoS ONE 8: e54945.
3. Frings, O. et al (2013) “MGclus: network clustering employing shared neighbors” Molecular BioSystems (in press).
4. Tjärnberg, A. (2013) “Optimal sparsity criteria for network inference” J. Computational Biology (in press)
Contact
Erik Sonnhammer
E-mail: [email protected]
Bioinformatics for network and systems biology
SciLifeLab Stockholm Annual report 2012 | 23
research program has also been established for collaborations between AstraZeneca and SciLifeLab associated groups.
Example of collaboration: GE Healthcare
The GE Healthcare DemoLab is a facility equipped with GE Healthcare’s instrumentation and reagents for life science research. This complements the instrumentation and competence provided by SciLife-Lab and facilitates collaboration between industry and academia. The instrumentation includes ÄKTA for purification and analysis of biomolecules, Biacore and MicroCal technology for biomolecular interaction analysis and the imaging systems Image Quant and Typhoon, and IN Cell Analyzer. During 2012, GE DemoLab has been carrying out a large number of projects together with research groups in the Stockholm-Uppsala region.
Based on the advanced technologies and instrumen-tation available, SciLifeLab Stockholm aims to be involved in the development of new techniques and instrumentation in collaboration with industry and to be a reliable and competent partner for develop-ment and testing of new technology. Several such collaborations are ongoing at SciLifeLab Stockholm.
Another interesting possibility for industrial collabo-ration is to get smaller companies to use the resources at SciLifeLab as means for increasing their interna-tional competitiveness. This will be based on a full-cost policy, but might still be attractive for some companies.
Finally, SciLifeLab Stockholm is an attractive partner for pharmaceutical industry in larger scientific studies. One interesting possibility here is to use the infrastructure built up in SciLifeLab along with Sweden’s unique clinical materials and skills to promote Sweden as a location for research on the major international pharmaceutical companies.
Example of collaboration: AstraZeneca
In June 2012, AstraZeneca started up the Translational Science Centre in collaboration with Karolinska Institutet. The center is situated at SciLifeLab Stockholm and will be focusing on finding biomarkers for different chronic diseases, such as cancer, rheumatoid arthritis, cardiovascular disease and dementia. A joint collaborative open
Collaboration with industry
GE Healthcare DemoLab.
Pho
to: S
taff
an E
liass
on
Collaborations between academia and industry are becoming increasingly important
and SciLifeLab Stockholm is working actively to find new forms of collaboration with
national and international industry partners. These collaborations have large
potential for societal gains in a wide range of applications. Examples range from a
faster route to convert new knowledge into products or therapies in medicine and
health care to new ways to produce biofuels.
24 | 2012 Annual report SciLifeLab Stockholm
The SciLifeLab Stockholm researchers
Adnane AchourAssoc. Prof., KIStructural and Biophysical Immunol-ogy.
Afshin AhmadianAssoc. Prof., KTHExperimental genomics.
Anders AnderssonAssoc. Prof., KTHMetagenomic analysis of microbial communities.
Björn AnderssonProf., KIGenomic analysis.
Lars ArvestadDr., SUComputational studies in evolution and genomics.
Helena BerglundAssoc. Prof., KIFacility Manager Protein Production.
Thomas HelledayProf., KITranslational cancer medicine and chemical biology.
Berk HessAssoc. Prof., SUComputational biophysics.
Lukasz HuminieckiAssoc. Prof., SUComputational biology statistics, bioinformat-ics and software development.
Annika Jenmalm Jensen Dr., KIFacility manager Chemical Biology. Director of Chemical Biology Consortium Sweden (CBCS).
Juha KereProf., KIMolecular genetics and biology of complex phenotypes.
Lukas KällAssoc. Prof., KTHStatistical biotechnol-ogy.
Mats NilssonProf., SUMolecular diagnostics.
Peter NilssonProf., KTHSite Director of Human Protein Atlas at SciLifeLab.
Jacob OdebergProf., KTH/KIClinically applied proteomics.
Bengt PerssonProf., KI/LiUDirector of BILS (Bioinformatics Infrastructure for Life Sciences). Protein families and structural properties.
Peter SavolainenAssoc. Prof., KTHEvolutionary studies of dogs based on DNA sequence analysis.
Jochen SchwenkAssoc. Prof., KTHFacility manager Biobank profiling. Biomarker discovery using antibody-based analysis of biobank samples.
SciLifeLab Stockholm Annual report 2012 | 25
Hjalmar BrismarProf., KTH/KIDevelopment of methods based on superresolution microscopy with applications in studies of membrane proteins and their integrative functions.
Jens CarlssonDr., SUComputational structural and chemical biology.
Arne ElofssonProf., SUStudies of protein structure, folding and evolution using mainly computational methods.
Olof EmanuelssonAsst. Prof., KTHBioinformatics of gene expression and protein localization.
Lars EngstrandProf., KIClinical bacteriology.
Gunnar von HeijneProf., SUVice Center Director. Experimental and bioinformatics studies of membrane proteins.
Jens LagergrenProf., KTHEvolution, probabilistic modeling, RNA editing, micro RNA, machine learning, and algorithm design.
Janne LehtiöAssoc. Prof., KIFacility manager Clinical Proteomics and Director of Karolinska University Hospital proteomics facility. In-depth analysis of proteome, mass spectrometry.
Erik LindahlProf., SU/KTHBiophysics. Modeling, simulation and electrophysiology studies of voltage- and ligand-gated ion channels. Leading the GROMACS interna-tional molecular simulation project.
Emma LundbergAssoc. Prof., KTHFacility manager Cell Profiling. Protein profiling of cells using antibody-based imaging.
Joakim LundebergProf., KTHDevelopment and application of novel methods for massively parallel DNA sequencing.
Jan MulderDr., KIFacility manager Tissue Profiling. Antibody-based mapping of regional and cellular protein distributions in the mammalian nervous system.
Erik SonnhammerProf., SUDirector of Stockholm Bioinformatics Centre. Prediction of protein function and interaction networks.
Jussi TaipaleProf., KIDirector of KHTC. Studies of the molecular mechanisms behind the develop-ment of cancer, including gene expression.
Mathias UhlénProf., KTHCenter Director. Leading the international effort to create a Human Protein Atlas.
Anna WedellProf., KIMedical genetics and discovery of novel monogenic diseases.
Roman ZubarevProf., KIMass-spectrometry based proteomics for biomedical research.
Björn ÖnfeltAssoc. Prof., KTHImmune cell diagnostics.
26 | 2012 Annual report SciLifeLab Stockholm
Contreras et al (2012), Nature 481 (7382): 525-9.Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain.
Darki et al (2012), Biol Psychiatry 72 (8): 671-6.Three Dyslexia Susceptibility Genes, DYX1C1, DCDC2, and KIAA0319, Affect Temporo-Parietal White Matter Structure.
Dengjel et al (2012), Mol Cell Proteomics 11 (3): M111 014035.Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens.
Ekdahl et al (2012), Genome Res 22 (8): 1477-87.A-to-I editing of microRNAs in the mammalian brain increases during development.
Elvers et al (2012), Nucleic Acids Res 40 (17): 8440-8.CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation.
Eriksson et al (2012), Blood Cancer J 2: e81.The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia.
Forslund et al (2012), Methods Mol Biol 856: 187-216.Evolution of protein domain architectures.
Fraser et al (2012), Clin Cancer Res 18 (4): 1015-27.PTEN deletion in prostate cancer cells does not associate with loss of RAD51 function: implications for radiotherapy and chemotherapy.
Groth et al (2012), Nucleic Acids Res 40 (14): 6585-94.Homologous recombination repairs secondary replication induced DNA double-strand breaks after ionizing radiation.
Gubanova et al (2012), Clin Cancer Res 18 (5): 1257-67.Downregulation of SMG-1 in HPV-positive head and neck squamous cell carcinoma due to promoter hypermethylation correlates with improved survival.
Guy et al (2012), Proc Natl Acad Sci U S A 109 (52): E3627-8.Genomic diversity of the 2011 European outbreaks of Escherichia coli O104: H4.
Aavikko et al (2012), Am J Hum Genet 91 (3): 520-6.Loss of SUFU Function in Familial Multiple Meningioma.
Abrahamsson et al (2012), J Allergy Clin Immunol 129 (2): 434-40.Low diversity of the gut microbiota in infants with atopic eczema.
Ahmad et al (2012), Mol Cell Proteomics 11 (3): M111 013680.Systematic analysis of protein pools, isoforms, and modifications affecting turnover and subcellular localization.
Alexeyenko et al (2012), Nucleic Acids Res 40: D821-8.Comparative interactomics with Funcoup 2.0.
Arabi et al (2012), Nat Commun 3: 976.Proteomic screen reveals Fbw7 as a modulator of the NF-kappaB pathway.
Bäcklund et al (2012), Ann Rheum Dis (in press).C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells.
Buus et al (2012), Mol Cell Proteomics 11 (12): 1790-800.High-resolution Mapping of Linear Antibody Epitopes Using Ultrahigh-density Peptide Microarrays.
Carlsson et al (2012), Methods Mol Biol 857: 313-30.Investigating protein variants using structural calculation techniques.
Chauhan et al (2012), Cancer Cell 22 (3): 345-58.A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance.
Chingin et al (2012), Anal Chem 84 (15): 6856-62. Separation of Polypeptides by Isoelectric Point Focusing in Electrospray-Friendly Solution Using a Multiple-Junction Capillary Fractionator.
SciLifeLab Stockholm – Scientific publications
During 2012, SciLifeLab Stockholm researchers have
produced more than 170 scientific publications. The list
below presents all peer-reviewed scientific publications
in journals with an impact factor of six or higher.
SciLifeLab Stockholm Annual report 2012 | 27
Hansson et al (2012), Lab Chip 12 (22): 4644-50.Inertial microfluidics in parallel channels for high-throughput applications.
Henrion et al (2012), Proc Natl Acad Sci U S A 109 (22): 8552-7.Tracking a complete voltage-sensor cycle with metal-ion bridges.
Hirvikoski et al (2012), J Clin Endocrinol Metab 97 (6): 1881-3.Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint.
Imai et al (2013), Methods Mol Biol 939: 115-40.Localization prediction and structure-based in silico analysis of bacte-rial proteins: with emphasis on outer membrane proteins.
Ismail et al (2012), Nat Struct Mol Biol 19 (10): 1018-22.A biphasic pulling force acts on transmembrane helices during translocon-mediated membrane integration.
Jones et al (2012), Oncogene (in press).Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress.
Kampf et al (2012), BMC Med 10: 103.A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas.
Kivioja et al (2012), Nat Methods 9 (1): 72-4.Counting absolute numbers of molecules using unique molecular identifiers.
Kjellqvist et al (2012), Mol Cell Proteomics 12 (2): 407-25.A combined proteomic and transcriptomic approach shows diverging molecular mechanisms in thoracic aortic aneurysm development in patients with tricuspid- and bicuspid aortic valve.
Lamminmaki et al (2012), J Neurosci 32 (3): 966-71.Human ROBO1 regulates interaural interaction in auditory pathways.
Larance et al (2012), Mol Cell Proteomics 11 (3): M111 014407.Characterization of MRFAP1 turnover and interactions downstream of the NEDD8 pathway.
Liebmann et al (2012), J Neurosci 32 (50): 17998-8008.A Noncanonical Postsynaptic Transport Route for a GPCR Belonging to the Serotonin Receptor Family.
Lindahl (2012), Proc Natl Acad Sci U S A 109 (52): 21186-7.Unraveling the strokes of ion channel molecular machines in computers.
Logue et al (2012), ISME J 6 (6): 1127-36.Freshwater bacterioplankton richness in oligotrophic lakes depends on nutrient availability rather than on species-area relationships.
Nikulenkov et al (2012), Cell Death Differ 19 (12): 1992-2002.Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis.
Nookaew et al (2012), Nucleic Acids Res 40 (20): 10084-97.A comprehensive comparison of RNA-Seq-based transcriptome analysis from reads to differential gene expression and cross-compar-ison with microarrays: a case study in Saccharomyces cerevisiae.
Öjemalm et al (2012), Mol Cell 45 (4): 529-40.Orientational preferences of neighboring helices can drive ER insertion of a marginally hydrophobic transmembrane helix.
Öjemalm et al (2012), J Cell Sci (in press).Positional editing of transmembrane domains during ion channel assembly.
Perisic et al (2012), Kidney Int 82 (10): 1071-83.Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics.
Punta et al (2012), Nucleic Acids Res 40: D290-301.The Pfam protein families database.
Renvall et al (2012), J Neurosci 32 (42): 14511-8.Genome-wide linkage analysis of human auditory cortical activation suggests distinct Loci on chromosomes 2, 3, and 8.
Sandberg et al (2012), Mol Cell Proteomics 11 (7): M112 016998.Tumor proteomics by multivariate analysis on individual pathway data for characterization of vulvar cancer phenotypes.
Slaats et al (2012), Allergy 67 (7): 895-903.DNA methylation levels within the CD14 promoter region are lower in placentas of mothers living on a farm.
Somaiah et al (2012), Clin Cancer Res 18 (19): 5479-88.The Relationship Between Homologous Recombination Repair and the Sensitivity of Human Epidermis to the Size of Daily Doses Over a 5-Week Course of Breast Radiotherapy.
Sur et al (2012), Science 338 (6112): 1360-3.Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors.
Tammimies et al (2012), Biol Psychiatry (in press).Molecular Networks of DYX1C1 Gene Show Connection to Neuronal Migration Genes and Cytoskeletal Proteins.
Uddenberg et al (2012), Plant Physiol 161 (2): 813-23.Early cone-setting in Picea abies var. acrocona is associated with increased transcriptional activity of a MADS-box transcription factor.
Uhlen et al (2012), Mol Cell Proteomics 11 (3): M111 013458.Antibody-based protein profiling of the human chromosome 21.
Wiklund et al (2012), Lab Chip 12 (18): 3221-34.Acoustofluidics 18: Microscopy for acoustofluidic micro-devices.
Wright et al (2012), Mol Cell Proteomics 11 (8): 478-91.Enhanced peptide identification by electron transfer dissociation using an improved Mascot Percolator.
Ying et al (2012), Cancer Res 72 (11): 2814-21.Mre11-Dependent Degradation of Stalled DNA Replication Forks Is Prevented by BRCA2 and PARP1.
Zeiler et al (2012), Mol Cell Proteomics 11 (3): O111 009613.A Protein Epitope Signature Tag (PrEST) library allows SILAC-based absolute quantification and multiplexed determination of protein copy numbers in cell lines.
See more publications at publications.scilifelab.se
28 | 2012 Annual report SciLifeLab Stockholm
The Platform Facilities
Facility Manager: Dr . Max Käller
Mission
• To provide a state-of-the-art infrastructure and
internationally competitive service for massively parallel
sequencing
• To provide a wide repertoire of sequencing applications
addressing the needs of national and international
customers
• To provide guidelines and support for sample collections,
study design and protocol selection
Description of service
The massively parallel DNA sequencing techniques can be
used for a variety of studies: whole genome sequencing,
exome sequencing, de novo sequencing, targeted sequenc-
ing of regions in single or multiple individuals, transcriptome
profiling including quantification, transcript isoforms and
miRNAs, ChIP-Seq to detect transcription binding sites
across the genome, amplicons sequencing (e .g ., 16S rRNA
genes), and metagenomic sequencing of microflora
genomes . The unit offers advice on project design, sample
preparation, and sequence analyses in collaboration with
the Genomics Bioinformatics facility . During 2012, the
sequencing capacity has been increased >3-fold to improve
the handling also of large sequencing projects .
As of Jan 1, 2013 the Genomics Platform operates three
facilities; Genomics Production, Genomics Applications and
Genomics IT, replacing Genomics Experimental and
Genomics Bioinformatics .
Infrastructure (selected)
• 5 Illumina HiSeq2500
• 2 Roche Genome Sequencer 454 FLX+
• 1 Life Technologies SOLiD 5500 XL
• 2 Illumina MiSeq
• 1 Argus Optical Mapper
Achievements 2012
• 207 projects completed
• 4539 samples processed
Contact
Genomics Production
Facility Manager: Dr. Ellen Sherwood
E-mail: [email protected]
Phone: +46 8 524 81483
Genomics Applications
Facility Managers: Dr. Max Käller and Dr.Valtteri Wirta
E-mail: [email protected] or
Phone: +46 8 524 81426 or +46 8 524 81545
Ordering (sample coordinator): Mattias Ormestad
E-mail: [email protected]
Phone: +46 8 524 81435
https://portal.scilifelab.se/genomics/
Genomics Experimental
SciLifeLab Stockholm Annual report 2012 | 29
• CLCbio server
• Access to computing and storage resources at UPPNEX
Software:
• BCBIO, semi-automatic software pipeline for data
management and best practice data analysis
• Adhoc, web service for analysis of proprietary
sequence data
• LIMS for management of lab data
• CLCbio, commercial software for analysis of NGS data
• Access to open source software for NGS data analysis
at UPPNEX
Achievements 2012
• Received and handled genomics data from 207 projects
and 4539 samples (an amount corresponding to on
average 82 GB per day)
• Establishment of improved best practice data analysis for
the sequencing applications provided by the Genomics
Experimental facility
• Contribution to relevant open source projects
• Successfully evaluated and received funding for establish-
ment of a national infrastructure for applied bioinformat-
ics (WABI)
Contact
Facility Managers: Dr. Thomas Svensson and
Dr. Per Kraulis
E-mail: [email protected] or
Phone: +46 8 524 81488 or +46 8 524 81465
The Platform Facilities
Facility Manager: Dr . Thomas Svensson
Mission
• To provide state-of-the-art data handling and storage
solutions for massively parallel sequencing data
• To offer best practice data analysis aligned to the sequenc-
ing applications provided by the Genomics Experimental
facility
Description of service
The facility is closely integrated with the Genomics Experimen-
tal facility and provides an automatic pipeline for transfer of
data from instruments to high-performance computing
resources . Users of the service can also benefit from a secure
web application allowing similarity searches of their own
sequence databases . The facility provides support in the form
of best practice bioinformatics analysis of genomics sequence
data, as well as applied bioinformatics analysis in various
biological contexts .
During the second half of 2012 the organization has adapted to
the 3-fold increase in data production, by focusing the informat-
ics resources on support for data production and improved best
practice analyses . The responsibility for user support of
advanced and applied bioinformatics has gradually been moved
to a new SciLifeLab facility called WABI (see more on page 44) .
Infrastructure (selected)
Hardware:
• 2 servers dedicated for sequence assembly with
1 and 2 TB RAM memory, respectively
• Dedicated servers for data management and software
development/testing
Genomics Bioinformatics
30 | 2012 Annual report SciLifeLab Stockholm
SciLifeLab Stockholm Annual report 2012 | 31
The Platform Facilities
Facility Manager: Assoc . Prof . Emma Lundberg
Mission
• To provide multiplex immunofluorescence and high-
resolution microscopy for analysis of the subcellular
distribution of proteins in a multitude of human cells
• To provide a publically available database of the sub-
cellular localization of all human proteins (Subcellular
Protein Atlas as part of the Human Protein Atlas)
• To validate the specificity of antibodies using siRNA
technology
• To provide expertise for immunofluorescence application
testing of antibodies
• To provide expertise for deeper quantitative analysis and
cell profiling in collaborative projects
Description of service
The cell profiling facility has equipment and expertise to
explore the subcellular distribution of the human proteome
using antibodies and confocal microscopy . The unit provides
expertise on antibody-based high-content imaging and
extraction of quantitative and qualitative information from
images . The main activity in the Cell profiling facility is to
generate a publically available database of subcellular
protein localization of the human proteome .
Infrastructure (selected)
• 37,000 antibodies validated (by protein arrays) from
the HPA project
• 3x Leica SP5 confocal microscopes with Screening
software
• 2x EVO150 liquid-handling robot
Achievements 2012
• 20,500 samples analysed (immunostained cell sample
prepared, imaged and analysed)
• > 100,000 confocal images acquired
• Established a platform for high-throughput validation of
antibody specificity using siRNA technology
• 15 peer-reviewed publications of which 9 related to
collaborative projects
• 10 service projects initiated (all with industry)
Contact
Facility Manager: Assoc. Prof. Emma Lundberg
E-mail: [email protected]
Phone: +46 8 524 81468
Cell Profiling
Pho
to: H
åkan
Lin
dg
ren
32 | 2012 Annual report SciLifeLab Stockholm
The Platform Facilities
Facility Manager: Assoc . Prof . Jochen Schwenk
Mission
• To provide multiplexed antibody- and antigen-based
profiling of body fluids
• To enable protein biomarker discoveries and verification
across diseases
• To provide profiling of autoimmune signatures
• To provide guidelines for sample collection and target
selection
• To support studies with data analysis and study design
Description of service
The Biobank profiling facility provides support for profiling of
body fluids on three levels: study design, protein profile
generation, and statistical analyses of data . During 2012, the
service infrastructure has expanded with collaborative
projects involving research groups in the Stockholm–Uppsala
region . These projects have involved both antigen-based
profiling for new autoimmunity targets and antibody-based
profiling to generate protein profiles from screening serum
or plasma . Differential profiles of potential biomarker
candidates were observed and are being verified in different
assays and technologies .
Infrastructure (selected)
• 37,000 antibodies validated (by protein arrays) from
the HPA project
• 37,000 antigens (MS verified) from the HPA project
• Whole proteome peptide arrays
• 2x EVO150 liquid-handling robot – Tecan
• SELMA 96-fold pipettor – CyBio
• LX200, MagPIX, FlexMap3D – Luminex
• Marathon inkjet microarrayer – ArrayJet
• Nanoplotter 2 .0E non-contact microarrayer – GeSim
• LuxScan HT 24 microarray scanner – CapitalBio
• G2565BA 48 slide microarray scanner – Agilent
• EL406 plate washer – Biotek
Achievements 2012
• > 10,000 antibodies in profiling of cancer and cardio-
vascular disease
• > 10,000 antigens in autoimmunity profiling within
multiple sclerosis
• Whole peptide arrays in autoimmunity profiling and
epitope mapping
• 7 peer reviewed publications
• > 20 national collaborative projects ongoing
• 1 service project initiated
Contact
Facility Manager: Assoc. Prof. Jochen M Schwenk
E-mail: [email protected]
Phone: +46 8 524 81482
Platform Director: Prof. Peter Nilsson
E-mail: [email protected]
Phone: +46 8 524 81418
Biobank Profiling
SciLifeLab Stockholm Annual report 2012 | 33
Infrastructure (selected)
• A PerkinElmer 3 arm Janus robotic liquid dispensing
system with 96 and 384 head
• An ECHO550 non-contact (tip less) liquid dispenser 96 to
1536 plate format
• Two human genome wide siRNA libraries (Dharmacon
and Ambion)
• Small molecule libraries (130K compounds)
• Cell cultivation laboratory
Selected Achievements 2012
• Identification through a genomic wide RNAi knockout
screen of a number of putative genes involved in Wnt-3
mediated signaling
• Identification putative systemic lethal genes through RNAi
knockout
• Kinase siRNA screen using the Surefire technology
• Network mapping of EGFR pathway through knockout
with selected siRNA screen and substance
• Identification of a number of novel chemical entities (hits)
in 7 different chemical screens
• Transfer and solid RNAi transfection and use in antibody
validation
Contact
Facility Manager: Dr. Bo Lundgren
E-mail: [email protected] or
Phone: +46 8 524 81470
The Platform Facilities
Facility Manager: Dr . Bo Lundgren
Mission
• To provide high-throughput RNAi knockout technology
to the Swedish research community
• To provide expertise in setting up high-throughput
microplate-based biological screening methods using
controlled and validated technology
Description of service
The RNAi Cell screening facility provides high throughput
RNAi-based screenings both as customized screens using a
number of selected sets of siRNAs as well as whole genome
wide screens . The facility is equipped with state-of-the-art
instrumentation, designated cell and robotic laboratories
and highly trained personal . The facility provides expertise
and technical support to the researcher on:
• Strategies for the experimental design
• Development of endpoint assay and help on statistical
analyses of the screening data
• Setup of the robotics and carrying out the high-
throughput screen in collaboration with the researcher
The experimental work is performed in a validated and
controlled technical environment . We also provide expertise
on in vitro toxicity, cell culture or pre-clinical issues .
Cell Screening
34 | 2012 Annual report SciLifeLab Stockholm
The Platform Facilities
Facility Manager: Dr . Dorothea Rutishauser
Mission
• To provide label-free quantitative proteomics analysis
using nLC/MS and low sample consumption (<1µg)
• To provide accurate mass determination (<2ppm)
• To provide de novo sequencing of polypeptides using
fragmentation methods CID, HCD and ETD
• To provide analysis of post-translational modification
• To provide bioinformatics analysis of MS data, including
quantitative Pathway Analysis
• To offer consultation on experimental design, sample
handling and MS data interpretation
Description of service
The advanced proteomics facility provides fee-for-service
analysis of a big variety of protein and peptide samples
including identification, quantitation and analysis of
post-translational modifications . The facility also supports
project planning, experimental design and development of
sample preparation procedures . The main focus of the
facility is the generation of comprehensive quantitative
proteomics data sets based on recently developed methods
in high-resolution mass spectrometry-based proteomics .
Infrastructure (selected)
• 2 Q Exactive mass spectrometers, Thermo Scientific
• LTQ Orbitrap Velos Pro ETD, Thermo Scientific
• LTQ Orbitrap XL ETD, Thermo Scientific
• Xevo TQ, Waters
• Robotics and ionization sources: Mulitprobe II; Perkin-
Elmer, TriVersa NanoMate; Advion, AP/Maldi; MassTech
Achievements 2012
• 46 new proteomics projects started
• Collaborator in two high-throughput interdisciplinary
metabolomics/proteomics projects
• In-house development of accurate label-free
quantification software
• Acquisition of AP/MALDI-source for high-resolution
MS systems
• Installation of one additional high-resolution
MS instrument including nano and normal flow
LC systems for metabolomics and proteomics projects
Contact
Facility Manager: Dr. Dorothea Rutishauser
E-mail: [email protected]
Phone: +46 8 524 87707
Advanced Proteomics
SciLifeLab Stockholm Annual report 2012 | 35
Infrastructure (selected)
The facility is equipped with the latest peptide separation
techniques and mass spectrometers with complementary
characteristics .
• MS LTQ Orbitrap Velos Pro, Thermo Scientific
• MS Orbitrap Q Exactive, Thermo Scientific
• Q-TOF 6540, Agilent
• 2xLC-Triple Q-MS (6410, 6490), Agilent
• MALDI-TOF/TOF, Applied Biosystems
• 6xUPLC/HPLC, Agilent
• EIF elution robotics, GE Healthcare
Achievements 2012
• 41 projects completed or ongoing
• Numerous cross platform projects initiated
• Several novel proteomics methods, experimental and
bioinformatics have been developed and published in
leading proteomics journals
• Data has been provided to many customers’ publications
in high ranked journals (MBIO, EMBO journal, JCB, MCP)
and as support to a number of grant applications
Contact
Facility Manager: Assoc. Prof. Janne Lehtiö
E-mail: [email protected]
Phone: +46 8 524 81416
The Platform Facilities
Facility Manager: Assoc . Prof . Janne Lehtiö
Mission
• To offer state-of-the-art technologies, education and
competence in proteomics for a wide range of applied
projects to elucidate biology and discover biomarkers
• To provide comprehensive proteome analysis to support
annotation of protein coding genomes, so called
proteogenomics
Description of service
The Clinical proteomics facility provides services to obtain
comprehensive quantitative proteomics data, data analysis
and high quality project support for scientifically sound
projects within systems biology and biomarker discovery .
We offer fee-for-service sample analysis, support to plan
and perform larger in-depth proteomics projects, e .g .
protein identification, post-translational modification
analysis and protein quantification in complex biological
mixtures . The unit provides expertise on mass spectrometry-
based proteomics, data handling and develops methods for
improved proteome analysis .
Clinical Proteomics
36 | 2012 Annual report SciLifeLab Stockholm
Pho
to: H
åkan
Lin
dg
ren
Infrastructure (selected)
• 2x MetaSystems fully automated slide scanning micro-
scopes with integrated classifier based on the fly image
analysis and stitching software
• Leica Bond RX autostainer (IHC and ISH)
• Multichannel western blot setup and image acquisition
(Bio-Rad Chemidoc)
Achievements 2012
• Generated >100 detailed maps of protein distribution in
the mouse brain each comprising of 30 images of brain
sections with a resolution of 500 megapixels showing
both regional and cellular distribution of proteins in the
brain
• Initiated >20 collaborative projects involving analyses of
protein expression and distribution in rodent and human
tissue samples . Diseases studied in these collaborative
projects include; Alzheimer’s disease, multiple sclerosis,
stroke, Huntington’s disease, Parkinson’s disease, cancer
and hypertension
Contact
Facility Manager: Dr. Jan Mulder
E-mail: [email protected]
Phone: +46 8 524 81421
The Platform Facilities
Facility Manager: Dr . Jan Mulder
Mission
• To provide a tissue profiling platform based on multiplex
fluorescence immunohistochemistry for the analysis of
regional and cellular distribution of proteins and their
co-existence with known cellular or pathological markers
• To create a publically accessible protein atlas of the mouse
brain utilizing the unique antibody library generated
within the Human protein atlas project
• To create image analysis pipelines based on existing image
analysis tools (ImageJ, Matlab, Cell profiler)
Description of service
We have generated an infrastructure optimised for the
large-scale visualisation of protein expression and distribu-
tion in the mouse brain (Protein atlas of the mouse brain) .
This infrastructure is available for collaborative service
projects that benefit from the available know-how on tissue
processing and multiplex staining procedures, automated
IHC or ISH or automated slide scanning microscopy .
Tissue Profiling
SciLifeLab Stockholm Annual report 2012 | 37
38 | 2012 Annual report SciLifeLab Stockholm
The Platform Facilities
Facility Manager: Dr . Annika Jenmalm Jensen
Mission
To provide expertise and infrastructure for the development
of chemical probes to Swedish research groups with the
goal to strengthen research within chemical biology
nationally and contribute to make Swedish research in this
area internationally competitive .
Description of service
Chemical Biology Consortium Sweden (CBCS) was estab-
lished in 2010 as a non-profit strategic infrastructure for
academic researchers across Sweden . CBCS is funded by
the Swedish Research Council, Karolinska Institutet and
SciLifeLab Stockholm . The organization coordinates, and
makes available, a powerful academic framework of
platforms for the discovery, development and utilization of
small-molecule probes for life-science applications . CBCS
provides expertise within assay development, computational
chemistry, cheminformatics, chemical library screening and
development, medicinal/enabling chemistry, target
identification and preclinical profiling .
CBCS can currently assist with the following techniques
and tools:
• Computational chemistry and modeling
• Assay development
• Screening of small-molecule libraries towards isolated
targets or cell lines
• Screening hit evaluation and confirmation
• Hit-to-probe optimisation
• Medicinal chemistry expertise
• In silico and in vitro Pharmacokinteics (ADME)
Infrastructure
CBCS has a state of the art infrastructure for assay develop-
ment, small-molecule screening, chemistry optimization of
hits and in silico and in vitro assays for ADMET (absorption,
distribution, metabolism, excretion, toxicity) predictions .
Achievements
Since CBCS activities started in 2010:
• More than 30 primary screens have been completed
• 3 in vivo proof-of-principle studies
• 13 publications
• 8 manuscripts in preparation
Contact
Facility Manager: Dr. Annika Jenmalm Jensen
Consortium Director, CBCS
E-mail: [email protected]
Phone: +46 8 524 80879
www.cbcs.se
Chemical Biology
SciLifeLab Stockholm Annual report 2012 | 39
Chemical Biology
In addition to the standard services PSF also provide
guidance in protein related issues and can take on minor
protein production related tasks in parallel to the standard
process .
Infrastructure (selected)
• Standard equipment for molecular biology and protein
production
• Instrumentation for protein crystallization and
characterization
Achievements 2012
• Performed protein production work for 31 different
research groups
• Performed 325 high-throughput purifications and
prepared > 700 expression plasmids
• Settled the working mode of the core facility and updated
methodologies
Contact
Facility Manager: Assoc. Prof. Helena Berglund
E-mail: [email protected]
Phone: +46 8 524 86 843
www.psf.ki.se
The Platform Facilities
Facility Manager: Assoc . Prof . Helena Berglund
Mission
• To provide high quality, high-throughput protein
production services
• To provide expertise in protein production, protein
characterization, and protein chemistry
Description of service
The protein production platform is part of the Protein
Science Facility (PSF) established in 2011 to provide the
scientific community with protein production services and
instrumentation for protein crystallization and biophysical
characterization . PSF is based on the methodology platforms
of the Structural Genomics Consortium hosted by Karolinska
Institutet 2005–2011 and joined SciLifeLab Stockholm in
2012 .
The set up is based on high-throughput methods for
production of His-tagged proteins produced in E. coli and
standard services include:
• High-throughput sub-cloning into various expression
vectors
• Small scale expression and solubility screening
• Lab-scale production cultures
• Two-step protein purification
• Proteolytic His-tag removal
• Documentation and quality measures accompany all
delivered results and materials
Protein Production
40 | 2012 Annual report SciLifeLab Stockholm
SciLifeLab Stockholm Annual report 2012 | 41
The Platform Facilities
Facility Manager: Assoc . Prof . Hans Blom
Mission
• To develop and implement new bioimaging technology
• To provide access to unique bioimaging instrumentation
• To provide expertise in bioimaging
• To support and educate bioimaging users
Description of service
The mission of the Advanced Light Microscopy (ALM) facility
is to provide scientists all over Sweden with open access to
state-of-the-art superresolution fluorescence microscopy for
nanoscale biological visualisation . The ALM facility provides
access to all superresolution modalities, including the STED,
PALM, SIM, and STORM technologies developed in the last
decade . Collaborative project management and transfer of
knowledge to individual researchers are supported,
including organization of workshops and courses in
superresolution microscopy .
Via the Swedish Bioimaging Network, the ALM facility is
coordinated as a superresolution bioimaging node on a
national level . In addition to being selected a national node
for superresolution microscopy, the ALM facility has during
2012 been an advanced bioimaging node in Europe via the
large ESFRI infrastructure project Euro-Bioimaging . Together
with the University of Turku in Finland we have implemented
routines for providing access to advanced bioimaging
equipment and superresolution expertise to north European
scientist .
Infrastructure (selected)
• Pulsed STED superresolution microscope
(~70 nm resolution in 1–2 channels)
• Gated CW-STED superresolution microscope
(~50–60 nm resolution in 1–2 channels)
• Gated dual-color Easy-STED superresolution microscope
(in-house development by Dr . Matthias Reuss)
• SIM superresolution microscope
(doubled resolution in all direction; four colors)
• PALM superresolution microscope
(~20–40 nm resolution in 1–2 channels)
• dSTORM superresolution microscope
(~20–40 nm resolution in 1–3 channels)
Achievements 2012
• Installation of commercial ELYRA superresolution system
from Carl Zeiss
• Host for the second superresolution user-club workshop,
co-organized with Leica Microsystems
• Over 20 national and international supported super-
resolution fluorescence microscopy projects
• Euro-Bioimaging superresolution proof-of-concept site
Contact
Facility Manager: Assoc. Prof. Hans Blom
E-mail: [email protected]
Phone: +46 8 524 81214
www.scilifelab.se/index.php?content=bioimaging
Advanced Light Microscopy (ALM)
Pho
to: H
åkan
Lin
dg
ren
42 | 2012 Annual report SciLifeLab Stockholm
The Platform Facilities
Facility Manager: Dr . Jianping Liu
Mission
• To provide access to unparalleled automated and
high-throughput equipment, reagents, expertise and
training in the field of systems biology, functional
genomics and drug discovery to the scientific community
Description of service
KHTC is home to one of the most sophisticated, state-of-
the-art analytical platforms in Europe . We can perform
large-scale functional genomics (cDNA and RNAi) and
compound screens in various cellular and biochemical
assays . We provide a number of high-capacity technologies
to analyse protein-protein and protein-DNA interactions as
well as next generation sequencing technology . KHTC
operates as a self-service facility where we assist with assay
development, automation and operation .
Infrastructure (selected)
• Highly integrated laboratory automation workstations and
advanced liquid handling robots
• Fully automated microscope, Acumen eX3 High Content
Imaging System and multilabel plate reader
• Illumina HiSeq2000 DNA sequencers
• High-throughput PCR instrument and a platform for
systematic evolution of ligands by exponential enrichment
(SELEX)
• Recombinant DNA cloning/colony picking platform and
high-throughput yeast replicator
• Collections of genome-wide siRNA and ORF libraries as
well as several comprehensive chemical compound
libraries
Achievements 2012
• Successful integration of the Acumen eX3 High Content
Imaging System
• Two compound screens were completed using functional
cellular assays
• 352 sequencing runs were completed
• RNA extraction protocol for RNA sequencing was
automated
• Three siRNA pre-screens are in progress
• Four siRNA screens, one cDNA screen and three
compound screens have been initiated
• Data generated at KHTC was used in four high impact
journal publications
Contact
Facility Managers: Dr. Anders Eriksson and
Dr. Jianping Liu
E-mail: [email protected] or [email protected]
Phone: +46 8 5858 66 58
Karolinska High Throughput Center (KHTC)
SciLifeLab Stockholm Annual report 2012 | 43
Achievements 2012
• Consultancy and infrastructure support in over
200 projects nation-wide
• Development of large-scale storage for NGS analyses in
collaboration with SNIC/UPPMAX
• Development of national mass-spectrometry proteomics
data storage
• Deployment of Fido – a robust web services framework for
providing bioinformatics tools – in collaboration with
SNIC/NSC
• Set up routines for data publishing
• Planning for Swedish ELIXIR node
Contact
BILS Director: Bengt Persson
E-mail: [email protected]
Support: [email protected] and http://biosupport.se
www.bils.se
The Platform Facilities
Mission
• To provide bioinformatics infrastructure and support for
life science researchers in Sweden
• To be the national contact point towards the new
European infrastructure for biological information, ELIXIR,
and related international collaborations
Description of service
BILS (Bioinformatics Infrastructure for Life Sciences) is a
distributed national research infrastructure with support
from the Swedish Research Council . BILS provides infrastruc-
ture to facilitate bioinformatics analyses including necessary
computational and storage resources (which are provided in
close collaboration with the Swedish Infrastructure for
Computing, SNIC) . Furthermore, BILS provides routes for
data publishing . BILS also provides bioinformatics expertise
in a number of areas and engages in training activities in
order to inform life science researchers about the possibili-
ties of bioinformatics .
Bioinformatics Infrastructure for Life Sciences (BILS)
44 | 2012 Annual report SciLifeLab Stockholm
The Platform Facilities
Through a grant from the Wallenberg foundation, SciLifeLab
Stockholm-Uppsala can now offer in-depth bioinformatics
support for projects running at SciLifeLab platforms as a
national service . The service will initially focus on genomics
sequence data analysis, including both medical and
non-medical projects . The basic ideas behind the service are:
• Any research group at a Swedish university can apply for
the service as an addition to a standard SciLifeLab project
support grant
• Granted applications will be offered help with bioinfor-
matics data analyses by experienced bioinformaticians for
at least 3 months
• The service is free of charge . One group member should
be assigned to work alongside the WABI personnel to
ensure transfer of know-how
Currently, the WABI staff consists of 10 full-time bio-
informaticians . They will be fully integrated members of
their assigned research projects during their time of service .
An important aspect of WABI is to achieve hands-on
knowledge transfer from the WABI bioinformaticians to the
applicant’s research group . It is also our intention to offer
members of the research group to spend time at SciLifeLab
to ensure an efficient learning process .
Contact
WABI-Stockholm Director: Prof. Gunnar von Heijne
E-mail: [email protected]
The Wallenberg Advanced Bioinformatics Infrastructure (WABI)
Pho
to: H
åkan
Lin
dg
ren
SciLifeLab Stockholm Annual report 2012 | 45
46 | 2012 Annual report SciLifeLab Stockholm
National Reference Committee
Prof . Bernt Eric Uhlin, Umeå University
Prof . Göran Larsson, Göteborg University
Prof . Jens Nielsen, Chalmers University
Prof . Karl-Eric Magnusson (chairman), Linköping University
Prof . Gunilla Westergren Thorsson, Lund University
Prof . Johan Schnurer, Swedish University of Agricultural Sciences
Prof . Stefan Ståhl, KTH Royal Institute of Technology
Prof . Henrik Grönberg, Karolinska Institutet
Prof . Neus Visa, Stockholm University
Prof . Bengt Westermark, Uppsala University
Annual report project team
Mikaela Friedman
Fredrik Sterky
Mathias Uhlén
Photo
Håkan Lindgren
Contact
General questions:
Fredrik Sterky, Site Director
Scientific communication and External relations:
Mikaela Friedman
Administration and personnel:
Martina Selander
More information:
www.scilifelab.se
Board 2012
Prof . Jan Andersson, KI (chairman)
Prof . Peter Arner, KI
Prof . Stefan Nordlund, SU
Prof . Ylva Engström, SU
Prof . Sophia Hober, KTH
Prof . Stefan Ståhl, KTH
Directors (appointed in the end of 2012)
Prof . Mathias Uhlen (KTH), Center Director
Prof . Gunnar von Heijne (SU), Vice Center Director
Prof . Jan Andersson (KI), Vice Center Director
Prof . Anna Wedell (KI), Scientific Director
Prof . Mats Nilsson (SU), Scientific Director
Prof . Helene Andersson Svahn (KTH), Scientific Director
Assoc . Prof . Fredrik Sterky, Site Director
Prof . Karin Dahlman-Wright, Site Director Huddinge
Scientific Advisory Board
Prof . Bertil Andersson, Singapore
Prof . Kai Simons, Germany
Prof . Janet Thornton, UK
Prof . Sören Brunak, Denmark
Prof . Jan Ellenberg, Germany
Prof . Svante Pääbo, Germany
Prof . Yoshihide Hayashizaki, Japan
Prof . Craig Venter, USA
Prof . Leroy Hood, USA
Prof . Richard Caprioli, USA
Prof . Stephen Friend, USA
Prof . Jonathan Knowles, Switzerland
Prof . Elaine Mardis, USA
Management of SciLifeLab Stockholm
SciLifeLab Stockholm Annual report 2012 | 47
Immunofluorescent staining of human U-2 OS osteosarcoma cells, using an antibody HPA036090 towards Tensin-1, shows positivity in focal adhesions.
48 | 2012 Annual report SciLifeLab Stockholm
SciLifeLab Stockholm Annual report 2012 | 3
SciLifeLab Stockholm has been formed jointly by the three Stockholm universities,
KTH Royal Institute of Technology, Karolinska Institutet (KI) and Stockholm University (SU),
and thus combines the profiles and strengths of these three institutions .
Read more at: www.scilifelab.se