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National Contact Point LIFESCIHEALTH
Dr. Wilfried Diekmann
Königswinterer Str. 522-524, 53227 Bonn
phone: +49 228 447 698, e-mail: wilfried.diekmann@dlr.de
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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FP6 project portfolio in pathogenomicsTP LSH, Major Diseases, Outcome 1st Call
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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FP6 project portfolio in pathogenomicsTP LSH, Major Diseases, Outcome 1st Call
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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Activity Code Areas addressed Instr.
LIFESCIHEALTH-1.1 Fundamental genomics
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 Combating major diseases
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
Activity Code Areas addressed Instr.
LIFESCIHEALTH-2.3 Confronting the major communicable diseases linked to poverty
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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FP6 project portfolio in pathogenomicsTP LSH, Applied Genomics, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Applied Genomics, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Applied Genomics, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Major Diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Major Diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Major Diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 2nd Call
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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FP6 project portfolio in pathogenomicsTP LSH, Poverty-related diseases, Outcome 2nd Call
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
Activity Code Areas addressed Instr.
LIFESCIHEALTH-1.1 Fundamental genomics
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 Combating major diseases
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
LIFESCIHEALTH-2.3 Confronting the major communicable diseases linked to poverty
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