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ERA-NET PathoGenoMics

Agenda: - Welcome and short Tour de table - Zsuzsanna Koenig (EC): JP concept in general - Anna Lönnroth (EC): activities of DG Research related to the JPI on AMR - Anna Vallstedt Haeger (Swedish Research Council): Presentation JPI on Antimicrobial Resistance - Marion Karrasch (FZJ): Presentation ERA-NET - Discussion

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

1. Introduction and ERA-NET project data 2. Workplan and selected activities 3. Future plans

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

The ERA-NET PathoGenoMics:

. “ and functional of human- pathogenic microorganisms” . funded by the European Commission FP 6 . Runtime: 2004 – 2009 -> extended to 31.08.2012 . Budget: 3 Mio Euro

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

13 ERA-NET PARTNERS = Funding Organisations from 9 countries + 7 affiliated partners (FR, LV, UK, SE, NO, MT, LI) from 7 countries

Finland Academy of Finland AKA France Germany Agence Nat. Federal Min. Austria de Recherche of Education Öster.-Wissen- ANR and Research Schafts Fonds BMBF FWF Hungary Institut Pasteur Hung. Academy of Research Fed. Min. for IP Science / Hung. Center Education and Juelich Research HAS FZJ BMWF Scientif. Res. Fund Portugal OTKA Port. National Spain Slovenia Science Min. of Min. of Higher Foundation Educ. and Educ., Science Israel FCT Science and Techn. Min.of Health MICINN MHEST CSO-MOH

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Boards and decisions

Network Steering Committee NSC: - Representatives of the funding organisations - Decisions: 1 vote per organisation Affiliated Partners

European External Advisory Board Coordinator: Commission Joint Secretariat EAB Karrasch Koenig

Executing Board EB: All WP leaders Implementation of the work plan

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Activities related to PathoGenoMics:

ERASysBio and ERASysBio Plus: “Towards a European Research Area for Systems Biology”

“Systems Biology of Microorganisms 2 - SysMO2”

“Coordination of European Research on Emerging and major Infectious Diseases of Livestock”

The Network of Excellence EuroPathoGenomics (EPG): 38 partners based in 13 different countries Coordinator: University of Wuerzburg, Germany M. Karrasch 23.10.09 ERA-NET PathoGenoMics

1. Introduction and ERA-NET project data 2. Workplan and selected activities 3. Future plans

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

ERA-NET Workplan

4 Activity Steps: 4 –transnational research activities

3 – Implementation of joint activities

2 – Strategic activities

1 – Systematic Exchange of information & best practices

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

WP 3 Strategic and analytic activities: Strategic Research Agenda

> collaboration with the NoE EuroPathoGenomics M. Karrasch 23.10.09 ERA-NET PathoGenoMics

WP 4 Economic exploitation and job creation: Innovation Strategy Paper

Strategy paper: ERA- NET Pathogenomics

Pathogenomics, Innovation and Public health

Executive summary The field of anti-infective drugs is facing a crisis due to three major factors: (a) are constantly developing resistance to existing drugs (especially at the hospital setting); (b) the development of new antibacterial agents is nearing a standstill (new antibacterial agents constitute merely 6 of 506 drugs disclosed in the developmental programs of the largest pharmaceutical and biotech companies in the U.S.); (c) a dearth of reliable diagnostic and monitoring tools for infectious disease complicates treatment and diminishes its efficiency. Despite the ever growing need for new antimicrobial agents, a number of factors make their development economically unattractive. First, health authorities agree on the need to limit the use of broad spectrum antimicrobials in order to minimize the selective pressure driving resistance. Second, the products are almost certainly short-lived, since resistance to the product is likely to rise with time. Third, aging of the Western population has shifted drug discovery efforts towards agents that treat chronic medical conditions. Finally, newly developed agents face a strong competition, due to the large number of antimicrobials already approved. M. Karrasch…… 23.10.09 ERA-NET PathoGenoMics

WP 6 Human resources development and mobility

PathoGenoMics PhD Award:

Aim: to recognize up to three PhD Award Winners 2009, Gothenburg outstanding PhD theses in the field of genome research on human-pathogenic microorganisms ( + fungi)

issued yearly for theses finished in the previous year

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

WP 9 Science and society issues

- > Raise publics awareness to research in PathoGenoMics by:

• An interactive teaching aid for students and the general public. • Expalanatory Brochures for the general public. • A grant scheme for "science to society" initiatives. • Numerous press releases and articles. • Newsletter to the scientific community.

Our website: www. pathogenomics-era.net

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

WP 7 Management concept and tools WP 8 Implementing transnational activities

Our main activity: Funding of Research projects

. 1st transnational call on PathoGenoMics in 2005/2006 . 2nd transnational call on PathoGenoMics in 2007/2008 . 3rd transnational call on PathoGenoMics in 2009/2010

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

. 1st transnational call on PathoGenoMics in 2005/2006:

44 proposals

-> 12 funded projects (2007-2010) including 84 funded research groups

Total funding volume: 16.6 Mio

Kick-off Meeting 2007, Cologne

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

. 2nd transnational call on PathoGenoMics in 2007/2008:

50 pre-proposals, 22 full proposals

-> 13 funded projects (2009-2012) including 77 funded research groups

Total funding volume:

Kick-off Meeting 2nd Joint Call 16.3 Mio € Status Seminar 1st Joint Call May 2009, Villa Vigoni

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

. 3rd transnational call on PathoGenoMics in 2009/2010:

50 pre-proposals

25 full proposals

Full proposal evaluation session on the 22nd September 2010: - XX projects suggested for funding

expected funding volume:

approx. 10 Mio €

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Funded projects of the 1st + 2nd call:

No. of funded topic projects Prevention / Vaccines / Genome variability 9 Functional genomics, target identification - 7 > (bacterial Antiifectives)

Diagnostics 3

Fungal projects 6

total 25

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Funded projects:

• Industrial participation: not required

• most projects are more basic-science projects

• few industrial partners, few projects with direct impact (product develoment, e.g. vaccine, diagnostic tool)

• “(bacterial) antiifectives” projects: new targets for potential drugs, almost nothing beyond that stage

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

1. Introduction and ERA-NET project data 2. Workplan and selected activities 3. Future plans

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Topic description: “Integrated Infection Biology” -> “ERA-INFECT”

-> involve all major funding organisations of the field in Europe (include all “major players” like Sweden, UK, Italy, Switzerland, Ireland, Czech Republic…)

-> include all microorganisms causing infectious diseases in humans* (bacteria, fungi, , protozoa) *(animals are covered by ERA-NET EMIDA)

-> integrates all state-of-the-art technologies (e.g. –omics/post-genomics, systems biology, synthetic biology etc.)

-> focus on basic, genome/post-genome based research related to infection biology

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Potential timetable for a new “ERA-INFECT”:

2009: first discussions among the ERA-NET partners and with EC

2010: topic suggestion via Programme Committee

2011: potential Call in the specific work programme 2012

09/2012: potential start of the new ERA-NET

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

JPI AMR

Is there an overlap with the aims / envisaged funding of the JPI AMR?

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

JPI AMR: research questions being addressed - Covered by ERA-NET projects?

1. Biology and dynamics of resistance: • Evolution and transmission • Typing of bacterial strains ( ) • Modelling and risk assessment • Novel targets ( )

2. Epidemiology and disease burden • Global epidemiology • Disease burden

3. Prevention of resistance and innovation of treatment options • Rapid diagnostics • Novel lead molecules ( ) • Treatment concepts

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Impact and added-value for a new ERA-NET:

• provide the scientific basis for solving major health problems related to infectious diseases, e.g. of antimicrobial resistance • work complementary to the Joint Programming initiative on Antimicrobial Resistance (JPI AMR) • work complementary to European Commission work programme on health • Collaborate with existing research initiatives, e.g. ERA-NET EMIDA, SysMO…

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Impact and added-value for a new ERA-NET:

• provide the scientific basisConclusion for solving: major health problems related to infectious diseases, e.g. of antimicrobial resistance • work complementary. No competition to the, butJoint taking Programmingadvantage initiativeof on the complementary scopes and approaches Antimicrobial Resistance (JPI AMR) • work complementary. „The microbial to Europeanchallenge Commission“ is big work programme on health-> the more we do the better! • Collaborate with existing research initiatives, e.g. ERA-NET EMIDA, SysMO…

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Thanks you for your attention!

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Why is PathoGenoMics so important?

. Infectious diseases still second highest killer worldwide (WHO Reports). . Antibiotic resistance increasing (e.g. MRSA) . Newly emerging pathogens (e.g. Clostridium difficile) . Global travel spreads new variants fast . remains a danger

Genome and Post-Genome research on pathogenic microorganisms will lead to: - New vaccines (e.g. S. pn., MRSA) -> prevention - New diagnostic tools -> detection and monitoring - New targets for new therapeutics -> treatment (e.g. new anti-fungals, new / better antibiotics)

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

potential collaboration with JPI AMR

-> ERA-NET focussed on basic research, based on the recent technological developments e.g. identification of potential new targets, new markers for diagnostics…

-> Only small overlap with JPI AMR -> ERA-NET complementary to JPI

-> JPI AMR calls could try to develop the results further into application in order to fight AMR (e.g. more application oriented research, PPPs, clinical trials etc.)

-> both initiatives could profit very much from each other: - ERA-NET: transfer of the projects’ results into application - JPI: taking advantage of the ERA-NET results

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

What is Joint Programming?

The overall aim of Joint Programming is to pool national research efforts in order to make better use of Europe's precious public R&D resources and to tackle common European challenges more effectively in a few key areas. It will follow a structured strategic process whereby Member States agree common visions and strategic research agendas to address major societal challenges.

How does it work?

• Developing a shared vision for the area; • Defining a Strategic Research Agenda (SRA) and SMART objectives (Specific, Measurable, Achievable, Relevant and Time-Bound); and • Preparing for implementation of the SRA by analysing the options, assessing expected impacts and defining the best mix of instruments to be used.

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Challenge: new vaccines Example 1: Streptococcus pneumoniae

-> vaccination since approx. 2002; vaccine covers 7 strains out of 91, but 90% of the AB resistant) -> almost eliminated these strains, but lead to an emergence of other AB resistant strains

Example 2: Neisseria meningitidis Serotype B

Example 3: MRSA (Methicillin resistant ) -> steadily increasing resistance rate, e.g. Germany 10-25% of the clinical Staph. aureus isolates

M. Karrasch 23.10.09 Prevention / Vaccines ERA/ Genome -NET PathoGenoMics(bacterial) Antiifectives Dia- variability gnostics Parasite and host genetic diversity in A comparative molecular analysis of GAS and GBS pathogenesis Helicobacter infections (HELDIVNET) Genome wide screening of the human Deciphering the intersection of commensal and extraintestinal Neisseria meningitidis for pathogenic E. coli proteins enhancing serum resistance A global RNAi approach to unravel eukaryotic host functions that and evaluation of their vaccine modulate bacterial infections (acronym RNAi-Net) potential Pathogenomic approach to explore the use of bacterial interference as alternative treatment of recurrent urinary tract infections ADHRES-Signature Project Identification of hot spots of divergence and rapidly changing genes within Shiga toxin-producing Large scale screening of potential key factors involved in the / virulence transition of Enterococcus faecalis Mechanisms and modulation of innate immune responses to Streptococcus pneumoniae and S. pyogenes Functional genomics of host-pathogen interactions using high-throughput screenings: a novel approach towards identifying therapeutic/prophylactic targets SPATELIS - Spatio-temporal analysis of -host protein interactions sncRNAomics - High throughput comparative sncRNAome analysis in major Gram- positive human : functional characterization by a systems biology approach and peptide nucleic acid drug design Exploring Protein Secretion within the bacterial matrix. Acronym: EPS-Matrix European Initiative to Fight Chlamydial Infections by Unbiased Genomics - ECIBUG – Pathogenomic of increased Clostridium difficile virulence Transcriptome-based Monitoring and Eradication of Chronic Chlamydial Infection - ChlamyTrans - Host-pathogen protein-protein interactomes and their influence on the host metabolome Development, prevention and early diagnostic detection of Clostridium difficile-associated pseudomembranous colitis - an M. Karrasch 23.10.09 interdisciplinary network ERA-NET PathoGenoMics

Fungal projects:

Pneumocystis Pathogenomics: unravelling the Colonization-to-Disease shift

Genomic Approaches to Unravel the Molecular Mechanisms of Pathogenicity in the Human Fungal Pathogen Candida glabrata - FunPath

Glycoshield: Surface Modulation of the Fungal & Host Response using a Genomic Approach

Systematic analyses of kinase and phosphatase function in morphological, environmental, and virulence responses of the human fungal pathogen Candida albicans

Transcriptional networks controlling virulence in filamentous fungal pathogens (TRANSPAT)

The cell wall as a target to improve antifungal therapy against Aspergillosis

M. Karrasch 23.10.09 ERA-NET PathoGenoMics

Challenge: new therapeutics

Example 1: New Antibiotics Results of the Glaxo-SmithKline study (nature reviews 2005): Screening for new antibacterial substances for 10 years, investment approx. 500 Mio €; outcome: -> nothing!

Example 2: Improvement of previously discarded substances -> elucidate the mode of action and side effects -> try to modify substance in order to avoid the previous problems

M. Karrasch 23.10.09