nationale kontaktstelle lebenswissenschaften 1 national contact point lifescihealth dr. wilfried...

Nationale Kontaktstelle

Lebenswissenschaften

1

National Contact Point LIFESCIHEALTH

Dr. Wilfried Diekmann

Königswinterer Str. 522-524, 53227 Bonn

phone: +49 228 447 698, e-mail: [email protected]

http://www.nks-lebenswissenschaften.de

ERA-NET PathoGenoMics

Constituent Assembly, October 13-15, 2004

Strategic supporting measures

to raise synergies with the European framework programmes and

to embedd PathoGenoMics into the European R&D Landscape



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Session overviewW. Diekmann Chair & Introduction

Rationale and objectives for strategic support measuresin PathoGenoMics

Current FP6 project portfolio in pathogenomics

Selected FP6 projects of high relevance to PathoGenoMics

M. Frosch EUROPATHOGENOMICSEuropean Virtual Institue for Functional Genomics of Bacterial

Pathogens (NoE)

M. Vicente microMatrixWorkshop on strategies to address antimicrobial resistance

through the exploitation of microbial genomics (SSA)

Cooperation with European associations/societies and other stakeholders

E. Ron FEMSFederation of Microbiological Societies

International perspectives

J. Hacker US Microbe ProjectShort statement on current developments



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Strategic supporting / supervision measures in ERA-NETs Rationale and objectives

ERA-NET

NoE

FP

Biotechnology Action Plan

National

programmes

“Strategic Supervision“ in an ERA-NET means to support the coherent

development of research activities with different range throughout Europe at

all relevant levels of integration.

This shall contribute to give a real meaning to the terms “subsidiarity“ and

“variable geometry“ for a specific field of research.

regional/national ↔ transnational ↔ community

Range

p

roje

ct

↔

pro

gra

mm

e

↔

pol

icy Integration



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• set-up of powerful communication & multiplication networks for the ERA-NET

• continually observe programme design and project portfolios beyond the ERA-NET

• raise awareness and embedd the ERA-NET in the European research policy community (in particular beyond the partner countries and in relevant programme-making bodies, as e.g. EAG for FP7 preparation)

• supervision of international development(e.g. INCO target countries, trans-Atlantic cooperation)

Strategic supervision in PathoGenoMics, Task 9.4Objectives and methodology

→ develop perspectives for financial integration with other programmes

→ in particular at EU level as FP 6&7, ETIs; but also EUREKA, ESF, …

→ linking with NCP network, industrial associations, scientific societies, …

→ show international cooperation perspectives



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a) Fundamental knowledge & basic tools for functional genomics in all organisms

Geneexpression

andproteomics

Structuralgenomics

Comparative genomics

andpopulationgenetics

Bio-informatics

Multidisciplinary functional genomics approaches to basic biological processes

i) Advanced Genomics and its applications for health

b) Application of knowledge and technologies in the field of genomics and biotechnology for health

New,safer,more

effective drugs(incl. pharmaco-

genomics)

Newdiagnostics

New in vitrotests to

replace animalexperimentation

New preventive and therapeutic tools

(somatic gene and celltherapies; stem cell and immunotherapies, etc.)

Innovative research in post-genomics with

high potential forapplication

ii) Combating major diseases

b) Cancer c) Poverty-related diseases

• HIV / AIDS• Malaria• Tuberculosis

Cardiovascular disease,diabetesand rarediseases

Resis-tance to

antibioticsand other

drugs

Brain anddiseases ofthe nervous

system

Human development

andthe ageing

process

a) Application-orientated genomic approaches

TP 1 Life Science, Genomics and Biotechnology for HealthProgramme structure and pathogenomics-relevant areas



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Activity Code Areas addressed Instr.

LIFESCIHEALTH-1.1 Fundamental genomics

LSH-2002-1.1.0-1/2 Topics for STREP/CA/SSA across the Fundamental genomics area in all organisms SSA, CA, STREP

LIFESCIHEALTH-1.2 Applied genomics

LIFESCIHEALTH-1.2.5

Innovative research in post-genomics

LSH-2002-1.2.5-3 Combinatorial biosynthesis as a tool for generating new drug candidates STREP

LIFESCIHEALTH-2 Combating major diseases

LIFESCIHEALTH-2.1.2

Combating resistance to antibiotics and other drugs

LSH-2002-2.1.2-1 Management of respiratory tract infections NoE

LSH-2002-2.1.2-3 Broadening the knowledge base on the molecular mechanisms behind resistance STREP,CA

LSH-2002-2.1.2-4Workshop on the structuring of European research activities to more effectively combat drug resistant hospital infections

SSA

LSH-2002-2.1.2-5Workshop on strategies to address antimicrobial resistance through the exploitation of microbial genomics

SSA

LIFESCIHEALTH-2.3 Confronting the major communicable diseases linked to poverty

LSH-2002-2.3.0-4 Tuberculosis vaccine development IP, NoE

LSH-2002-2.3.0-5 Development of mucosal vaccines for poverty-related diseases IP, NoE

1st Call (FP-2002-LIFESCIHEALTH, deadline: 25.03.2003)Selected pathogenomics-relevant areas



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FP6 project portfolio in pathogenomicsTP LSH, Fundamental Genomics, Outcome 1st Call

Bacterial stress management relevant to infectious diseases and biopharma-ceuticals (BACELL HEALTH) – STREP, retained for funding

Integrated study of the response of Gram-positive bacteria to stresses encountered by pathogens during infection and by industrial strains during industrial bioprocesses:

• understand and model regulatory networks/processes that comprise cell stress management systems

• identify key targets for novel anti-infectives and improving industrial bioprocesses

Species: Bacillus subtilis, B. anthracis, B. cereus; Listeria monocytogenes, Staphylococcus aureus, Streptococcus pneumoniae

Coordination: University Newcastle, UK



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FP6 project portfolio in pathogenomicsTP LSH, Applied Genomics, Outcome 1st Call

Development of New Gyrase Inhibitors by combinatorial biosynthesis (COMBIGYRASE) – STREP, retained for funding

Generation of novel inhibitors of gyrase and topoisomerase IV, in particular of the aminocoumarin and cyclothialidine type

• engineering complete biosynthetic pathways of natural inhibitors

• cloning and sequencing of complete gene clusters

Species: Streptomyces spec.

Methodology: Biophysics, X-ray crystallography, enzyme and antibacterial assays, animal experimentation

Coordination: University Tübingen, DE



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FP6 project portfolio in pathogenomicsTP LSH, Major Diseases, Outcome 1st Call

Combating resistance to antibiotics by broadening the knowledge on molecular mechanisms behind resistance to inhibitors of cell wall synthesis (COBRA)– STREP, retained for funding

Elucidation of molecular mechanisms of resistance to inhibitors of cell wall synthesis in bacteria responsible for severe nosocomial and community-aquired infections:

• indepth understanding of resistance mechanisms based on ß-lactamases, penicillin-binding proteins, t-RNAdependent ligases, and other principles

• assess the modification of structure, function, dynamics of relevant pathways

• develop novel diagnostic and therapeutic tools

Species: Pseudomonas, Acinobacter, S. pneumoniae, S. aureus, Enterococcus

Methodology: structural genomics, crystallography, biochemistry,clinical microbiology, genetics

Coordination: INSERM, FR



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Molecular mechanisms of resistance, virulence and epidemicity in Streptococcus pneumoniae (PREVIS) – STREP, retained for funding

Identification of bacterial genetic determinants and host factors associated with invasise disease, drug resistant pneumococcal clones and spread of epidemic S. pneumoniae clones

• frequency and clonal types of drug resistant and drug susceptible pneumococci

• old age homes and AIDS hospice as ecological reservoirs of resistant strains

• transcriptional profiling involving DNA microarrays

• sequencing of S. mitis, a frequent source of gene fragments resulting in resistance

• threshhold levels of antibiotic consumption in the community

Species: Streptococcus pneumoniae

Methodology: genomics, transcriptomics, clinical microbiology

Coordination: Swedish Institute for Infectious Disease Control, SE



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Workshop on strategies to address antimicrobial resistance through the exploitation of microbial genomics (micro MATRIX) – SSA, retained for funding

Workshop to organise the European expertise needed to further apply functional genomics for fighting antimicrobial resistance:

• reveal novel anti-microbial targets

• discover new antibiotics

• understand the controls required to avoid the emergence of resistances

• discover regulatory notes and structural elements essential for resistance

• form a framework of leading experts and a concerted approach for further research

Methodology: gene expression, physiology, stress response, adhesion, pathogenesis, and resistance mechanisms,

Coordination: Consejo Superior de Investigaciones Científicas (CSIC), ES



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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 1st Call

An Integrated project for the design and testing of vaccine candidates against tuberculosis: Identification, development and clinical studies (TB-VAC)– IP, retained for funding

Development of improved TB vaccines, particularly for the young adult population:

• identify and develop novel vaccines or antigen components

• optimize the delivery and composition of candidate vaccines

• evaluate candidate vaccines in animal models as well as in Phase I clinical trials

• GMP production of vaccine candidates

Coordination: Institut Pasteur, FR



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LIFESCIHEALTH-1.1.3 Comparative genomics and population genetics

LSH-2003-1.1.3-2Standardisation and integration of genomic and phenotypic information to characterise bacterial diversity with relevance to human health

NoE

LSH-2003-1.1.0-1/2/3 Topics for STREP/CA/SSA across the Fundamental genomics area in all organisms SSA, CA, STREP

LIFESCIHEALTH-1.2 Applied genomics

LIFESCIHEALTH-1.2.5 Innovative research in post-genomics

LSH-2003- 1.2.5-2 Post-genomic approaches to the study of human pathogens NoELSH-2003- 1.2.5-4 New bioassays & biosensors using post-genomic approaches to detect harmful microbes STREPLSH-2003- 1.2.5-5 The fungal cell-wall as a target of antifungal therapies STREP

LSH-2003- 1.2.5-6Biotechnological & post-genomic approaches for the development of novel biosafe propagation deficient virus vectors aimed at prevention & treatment of infectious diseases (e.g. enteric, respiratory)

STREP

LSH-2003- 1.2.5-7 Exploitation of fungal genomics and filamentous fungal biotechnology for human health CA


LIFESCIHEALTH-2.1.2 Combating resistance to antibiotics and other drugs

LSH-2003-2.1.2-1 Functional genomics of antibiotics-producing organisms IP

LSH-2003-2.1.2-2New molecular targets to develop drugs against pathogens causing severe resistance problems

IP

LSH-2003-2.1.2-3Novel approaches to address antimicrobial resistance through non-antimicrobial based therapies

STREP, CA

2nd Call (FP-2003-LIFESCIHEALTH-I, deadline: 13.11.2003)Selected pathogenomics-relevant areas



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2nd Call (FP-2003-LIFESCIHEALTH-3, deadline 24.03.2004)Selected pathogenomics-relevant areas



LSH-2003-2.3.0-1Highly innovative approaches for the development of new interventions for HIV, malaria and tuberculosis

STREP

LSH-2003-2.3.0-2Coordination of European research on HIV, malaria and tuberculosis at the global level

SSA

LSH-2003-2.3.0-3 Networking of European SMEs active in the area of poverty related diseases SSA



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FP6 project portfolio in pathogenomicsTP LSH, Fundamental Genomics, Outcome 2nd Call

Genetics of Sepsis in Europe (GenOSept) - STREP, retained for funding

Multidisciplinary fundamental genomics approach to examine genetic predisposition to sepsis (life threatening infection)

• identify candidate genes including those controlling programmed cell death

• epidemiology studies of genetic disposition to sepsis-related mortality andmorbidity in European intensive care units

• gender-related aspects of sepsis patients

• target risk subpopulations

Methodology: gene expression, structural genomics, population genetics,genetic epidemiology, biometrics, high-throughput genotyping

Coordination: European Society of Intensive Care Medicine (ESICM), BE



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FP6 project portfolio in pathogenomicsTP LSH, Functional Genomics, Outcome 2nd Call

Functional genomic characterization of the bacterial Tat complex as a nanomachine for biopharmaceutical production and a target for novel anti-infectives (Tat machine) – STREP, retained for funding

Multidisciplinary functional genomic characterization of the Twin-arginine translocation (Tat) machinery, which is a widely conserved system for bacterial protein secretion:

• improve and use the Tat nanomachine for biopharmaceutical production

• use the Tat nanomachine of major Gram-positive and -negative pathogens as potential target for novel anti-infectives

Species: Bacillus, E. coli, Streptomyces, E. coli O 157,Pseudomonas aeruginosa

Methodology : bioinformatics, comparative and structural geniomics, proteomics

Coordination: University of Groningen, NL



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FP6 project portfolio in pathogenomicsTP LSH, Applied Genomics, Outcome 2nd Call

European Virtual Institute for Functional Genomics of Bacterial Pathogens – (EUROPATHOGENOMICS/EPG) - NoE, retained for funding

Network to form a durable alliance of the best pathogenomics research capacities

• bring together relevant epidemiological, basic and applied research

• stimulate collaborative, multidisciplinary research activities

• foster biotechnological applications and technology transfer (in terms of innovative diagnostic tools, anti-infectious agents, antigens and/or host defence mechanisms)

Methodology : molecular biology, immunology, cell biology, structural biology

Coordination: University of Würzburg, DENationales Kompetenzzentrum “Genomanalyse pathogener Mikroorganismen“



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Electrical bio sensor arrays for analyses of harmful microorganisms and microbial toxins (eBIOSENSE) - STREP, retained for funding

Advanced technology platform for analysis of food and water born harmful microorganisms and /or their toxins (e.g. mycotoxins):

• electric biochip arrays enabling the parallel and simultaneous identification of nucleic acids, microbial proteins and toxins (based on nm-sized interdigital gold electrodes)

• design of portable instruments furnished with disposable chips

Species: Escherichia coli (STEG, ETEC, EHEC), Salmonella enteridis,Bacillus cereus, Staphylococci, Legionella

Methodology : genomics, proteomics,bioinformatics, advanced silicon andmicrosystem technologies

Coordination: Kungliga Tekniska Högskolan, SE



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SLIC-Biosensors in Molecular Diagnostics: Nanotechnology for the analysis of species-specific microbial transcripts (SLIC) - STREP, retained for funding

Development of alternative technologies for direct genotyping and/or screening of the transcriptome for multiparametric testing systems usable in clinical diagnostics:

• use of tmRNA transcripts of the bacterial ssrA gene

• based on a self-assembled lipid bilayer membrane that integrates a synthetic ligand-gated ion-channel (so-called SLIC-Nanobiosystem)

• monitoring via electrical impedance sopectroscopy

• ultra-sensitive qunatification and identification of bacterial species in a single homogenous assay format

• prototypes of miniaturized/compact and cost-effective instruments

Methodology: transcriptomics, genomics, electronics

Coordination: Ayanda Biosystems, CH



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The fungal cell wall as a target for antifungal therapies (FUNGWALL)- STREP, retained for funding

Research programme on core cell wall complexes which are common to all pathogenic fungi:

• characterise the enzymes and reactions associated with chitin synthesis,glucan branching and cross-linking of chitin and 1-3 glucan

• signalling mechanisms allowing fungi to adapt to/survive cell wall damages

• define novel antifungal targets and compounds effecting cell wall integrity

Species: Candida albicans, Aspergillus fumigatus

Coordination: Institut Pasteur, FR



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FP6 project portfolio in pathogenomicsTP LSH, Major Diseases, Outcome 2nd Call

Integrating genomics-based applications to exploit Actinomyces as a resource for new antibiotics (ActinoGEN) - IP, retained for funding

Genomics-based approach to exploit hitherto overlooked genetic resources for new antibiotics:

• assess new biosynthetic pathways from diverse species

• activate cryptic pathways from well-characterised species

• engineer novel hybrid antibiotics by combinatorial biosynthesis

Methodology: multidiscipliar post-genomics, biochemistry, physiology, chemistry

Species: Actinomycetes,in particular Streptomyces coelicolor (genome completely sequenced)

Coordination: University of Wales Swansea, UK



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Inhibition of new targets for fighting antibiotic resistance (EUR-INTAFAR)- IP, retained for funding

Coherent set of converging approaches to study and design novel targets (i.e. enzyme inhibitors and/or agents perturbing protein-protein interactions) interfering with bacterial peptidoglycan biosynthesis and cell morphogenesis:

• inhibitors for penicillin-resistant transpeptidases

• inhibitors of the glycosyltransferase domain of class A penicillin-binding proteins

• inhibiting synthesis and transport of cell wall subunits at the plasma membrane

• interfering cell morphogenesis and its regulation

Methodology: biotechnology, bacterial physiology, cell biology

Species: streptocooci, staphylococci, enterococci, chlamydiae

Coordination: Université de Liège, BE



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New methods of treatment of antibiotic-resistant pneumococcal disease (PNEUMOPEP) - STREP, retained for funding

New targets/lead compounds as well as adjunctive therapy and drug delivery approaches against pneumonia and meningitis (including the related acute toxaemia caused by pro-inflammatory pneumococcal toxins as e.g. pneumolysin):

• targets: pneumolysin; cell surface proteinases involved in adhesion and invasion

• treatment approach based on binding peptides and small molecules isolated from large phage display libraries

• drug formulation in chitosan for nasal delivery

• pharmacological testsin animal models of pneumonia, bacteraemia and meningitis,

Species: multiresistant strains of Streptococcus pneumoniae

Coordination: University of Leicester, UK



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Antimicrobials by Immune Stimulation (AMIS) - STREP, retained for funding

Innovative approach to use the strength of the human immune system to design new antimicrobial drugs and/or to broaden the approaches in therapeutic intervention:

• Target: antimicrobial proteins that trigger inflammatory signals(i.e. in one single molecule)

• Screen and modify novel “dual mode of action effector molecules”as potential drug candidates

Species: various extra- and intracellular bacteria

Coordination: University Medical Centre Utrecht, NL



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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 2nd Call

Finding promising drug candidates against tuberculosis with multidisciplinary protocol based non-conventional search (scrIN-SILICO)– STREP, retained for funding

Development of a protocol capable of identifying novel drug binding sites and noveldrug-protein complexes of Mycobacterium tuberculosis proteins consisting of:

• a method to identify surface indentation patterns in protein 3D structures

• structural & molecular biology protocol for examining promising drug- protein fit pairs

Coordination: Eotvos Lorand Tudomanyegyetem, HU



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Genome- and HLA- wide scanning and validation of cytotoxic CD8 T cellresponses against Mycobacterium tuberculosis (VACCINES4TB)– STREP, retained for funding

Genomics/proteomics based platform for antigen- and epitope-discovery withrelevance to human immune CD8 cytotoxic T cells responses against M. tuberculosis

Methodology: high-throughput methods from immunology and bioinformatics

Coordination: Technical University of Denmark, DK



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Molecular markers of M. tuberculosis early interactions with host phagocytes (MM-TB) – STREP, retained for funding

Comparative genomics approach to develop new markers of protection and to identify novel molecular patterns, both in the microbe and in the host cells, being associated with early interactions between M. tuberculosis and phagocytic cells

• microarrays to simultaneously study the entire expressed genomes of both the mammalian host (macrophages, dendritic cells) and the microbial parasite during their interaction• reveal patterns of the induced gene expression • novel targets for vaccine design• molecular markers and pathways associated with protection

Methodology: transcriptional profiling approaches

Coordination: Technical University of Denmark, DK



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Development of a molecular platform for the simultaneous detectionof Mycobacterium tuberculosis resistance to rifampicin and fluoroquinolones(TB-DRUG OLIGOCOLOR) – STREP, retained for funding

Molecular platform for the identification of Mycobacterium tuberculosis in clinical specimens and simultaneous detection of resistance to rifampicin & fluoroquinolones:

Methodology: microplates, enzymatic chromogen detection systems

Coordination: Institute of Tropical Medicine, BE



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Strategy for characterisation of the worldwide population structure of Mycobacterium tuberculosis in relation to the efficacy of new tuberculosis vaccines (TB World Collection) – SSA, retained for funding

Preparing a strategy for collecting isolates in a non-biased way in order to characterise the worldwide population structure of M. tuberculosis:

• meeting of relevant specialists and contacts from developing countries

• develop a strategy for determining the evolutionary divergence worldwide

• standard set of most significant strains regarding the current TB epidemic

Coordination: National Institute of Public Health and the Environment, NL



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The diversity of Mycobacterium tuberculosis strains in China: tracing the origins of the worldwide dispersion of the multidrug-resistant Beijing genotype(TB China) – SSA, retained for funding

Organization of the analysis of a large collection of strains (3000) from the 31 Provinces of China:

• genotyping and multidrug-resistance (MDR) assessment

• clinical information as e.g. BCG status, age and gender of the patients

• technical knowledge exchange to Chinese laboratories

Coordination: University of Paris, FR



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Establishing a TB Treatment Efficacy Marker (TB Treatment Marker)– SSA, retained for funding

Strategy development for monitoring TB progression and the efficacy of TB treatment as well as for guiding clinical decision-making in TB management

• blood plasma protein suPAR level as a potential useful marker

• pilot study in Guinea-Bissau (one of the highest TB incidences in the world !)

Coordination: ViroGates ApS, FR



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3rd Call (FP-2004-LIFESCIHEALTH-5, deadline: 16.11.2004)Selected pathogenomics-relevant areas



LSH-2004-1.1.0-1/2/3 Topics for STREP/CA/SSA across the Fundamental genomics area in all organisms SSA, CA, STREP

LIFESCIHEALTH-1.2 Applied genomics LIFESCIHEALTH-1.2.5 Innovative research in post-genomics

LSH-2004-1.2.5-4 Post genomic approaches for tackling complex multifactorial diseases (except Cancer) STREP


LIFESCIHEALTH-2.1.2 Combating resistance to antibiotics and other drugs

LSH-2004-2.1.2-1 Management of lower respiratory tract infections NoELSH-2004-2.1.2-2 The role of mobile genetic elements in the generation of antimicrobial resistance STREP

LSH-2004-2.1.2-3Improved understanding of ecological factors with impact on the genetic and molecular determinants of fitness and virulence of resistant bacterial pathogens

STREP

LSH-2004-2.1.2-4 Control of anti-fungal drug resistance (especially orientated towards SMEs) STREP

LSH-2004-2.1.2-5Workshop on translation of research results on antimicrobial resistance into clinical practice

SSA

LSH-2004-2.1.2-6 Workshop for set up of a centrally supported system for annotation of microbial genomics SSA

LIFESCIHEALTH-2.2 Combating cancer

LSH-2004-2.2.0-3 Research on tumours associated with infectious agents IP


LSH-2004-2.3.0-4 Development of new drugs for the treatment of tuberculosis IPLSH-2004-2.3.0-7 Research in poverty-related diseases (PRD) by SMEs STREPLSH-2004-2.3.0-9 Coordination of PRD activities between biotech industry, bioincubators & biotech investors CA

nationale kontaktstelle lebenswissenschaften 1 national contact point lifescihealth dr. wilfried...

Documents

embedd pathogenomics

relevant programme

supervision measures

european associationssocieties

innovative research

eranets rationale

eranetraise awareness

european framework programmes