Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office: Dr. Michael Raess, Dr. Ana de Castro Helmholtz Zentrum München European Strategy Forum on Research Infrastructures www.infrafrontier.eu ESFRI roadmap First roadmap in 2006 • • • • 35 projects BBMRI – biobanking EATRIS – translational research ECRIN – clinical trials ELIXIR – bioinformatics • Infrafrontier – animal disease models • INSTRUCT – structural biology Update in Dec 2008 www.infrafrontier.eu + 10 projects • • • • EU-OPENSCREEN – chemical biology BLS4 – high security labs Euro-BioImaging - bioimaging EMBRC – marine biology Grand Challenges - Understand genetic and environmental impact on human health - Develop novel strategies for diagnosis, prevention and therapies www.infrafrontier.eu Why mouse? • Mouse genome fully sequenced • 95% similarity of the genes of mice and men • Easy to breed and handle in captivity • Extensive toolbox for manipulating the mouse genome Current Biology www.infrafrontier.eu Why mouse? Publications on ‘Mouse Models’ Mouse models achieve high impact www.infrafrontier.eu The challenge Shortage on capacities and access: Phenotyping (characterising mouse models) • Mouse Clinics EUMODIC, Infrafrontier Archiving and Dissemination of mice and data • Repositories EMMA, Infrafrontier www.infrafrontier.eu Required capacities • Phenotyping European Phenotyping Capacities Mouse Lines / year 1750 1500 1250 1000 750 500 250 0 '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13 • Archiving and distribution EMMA Requests (total) EMMA Submissions (total) 7000 7000 6000 1500 p.a. 5000 4000 3000 2000 420 p.a. 1500 p.a. 5000 4000 3000 2000 350 p.a. 1000 1000 0 0 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13 www.infrafrontier.eu Mouse Lines Mouse Lines 6000 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13 Infrafrontier: two main parts Infrafrontier Phenomefrontier Archivefrontier Archivefrontier/EMMA Systemic Phenotyping Archiving / Distribution + emerging centres + emerging centres Access to phenotyping data and mouse models Access to phenotyping services, data and mouse models www.infrafrontier.eu Capacity building required! www.infrafrontier.eu Osteogenesis imperfecta A group of genetic bone disorders ... Noted People with OI • Jazz pianist Michel Petrucciani • Actor writer and ethicist Peter Radke... In the mouse model: Bisphosphonate treatment … reverses bone phenotype … but does not lower mortality www.infrafrontier.eu The German Mouse Clinic Nature Methods 2005, Nature Genetics 2005, Nature Genetics 2008, Cell 2009 www.mouseclinic.de www.infrafrontier.eu Mouse model for Osteogenesis imperfecta - Mutation in collagen I Bone phenotype • Mineralisation defect • Bone deformity • fractures • Beaded ribs • Reduced Bone mineral content & decreased bone mineral density Systemic • Lung phenotype • Heart phenotype • Reduced fat mass & increased lean mass • Metabolic alterations www.infrafrontier.eu Infrafrontier partners 12 European Countries + Canada Research Institutions + Funding Agencies www.infrafrontier.eu Infrafrontier partners www.infrafrontier.eu Smaller Project Large Project www.infrafrontier.eu Very large Project: International Mouse Phenotyping Consortium (IMPC) www.infrafrontier.eu Infrafrontier and IMPC Keep in mind: • Infrafrontier is a BMS research infrastructure, NOT a single project • Infrafrontier has a different and broader portfolio than IMPC (infrastructure for bottom-up and top-down projects) • State of the art research infrastructures are highly dynamic entities www.infrafrontier.eu Infrafrontier preparatory phase Official start: 36 months until: 01 March 2008 28 February 2011 4.5 Mio € funding by the European Commission www.infrafrontier.eu Infrafrontier implementation www.infrafrontier.eu Infrafrontier implementation www.infrafrontier.eu Access to mouse resources and data www.infrafrontier.eu Operation Costs ES Cell Distribution ? € per line User Fees 500 –700 € Mouse Archiving 3,500 – 4,400 € per line Mouse Distribution 1,100 – 2,100 € per line User Fees 1,100 – 1,700 € Cohort Breeding 23,000 – 30,000 € per line Phenotyping 15,000 – 20,000 € per line www.infrafrontier.eu User Fees to be developed New mouse clinics and EMMA nodes Established facilities New facilities www.infrafrontier.eu Funding Strategy Integration of national & European funds National infrastructure funds National and European Projects Technology Development Operation Personnel Physical Infrastructure www.infrafrontier.eu Decentralised funding model European Commission Central Coordination MS MS MS MS MS MS MS = Member State www.infrafrontier.eu Governance Infrafrontier ERIC (Boards) www.infrafrontier.eu Governance Infrafrontier ERIC (Tasks) www.infrafrontier.eu More Information …. www.infrafrontier.eu Resource Sharing Policy The Rome Agenda: • “Funding organizations should … cover the costs of deposition of materials arising from projects as part of the project budget.” • “Funding agencies should … ensure appropriate datasharing plans at the outset of projects …” www.infrafrontier.eu More Information …. Coordinator: Prof. Dr. Martin Hrabé de Angelis hrabe@helmholtz-muenchen.de Project Office: Dr. Michael Raess Dr. Ana de Castro infrafrontier@helmholtz-muenchen.de Helmholtz Zentrum München Institute of Experimental Genetics Ingolstädter Landstrasse 1 85764 Neuherberg www.infrafrontier.eu Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office: Dr. Michael Raess, Dr. Ana de Castro Helmholtz Zentrum München Scope of Activities www.infrafrontier.eu Constructing Required Capacities EMMA Repository Initial Investment (100 mouse lines): ~ 6,600,000 € for Construction ~ 2,000,000 € for Equipment Adding capacities for 100 lines ~ 1,300,000 € Mouse Clinics Initial Investment (100 mouse lines): ~ 15,000,000 € for Construction ~ 5,000,000 € for Equipment Adding capacities for 100 lines ~ 6,500,000 € www.infrafrontier.eu Maintaining Capacities EMMA Repository Cryo-Archive (100 mouse lines): ~ 10,000 € per year Maintaining and Updating Equipment ~ 10% of Purchasing Price per year Mouse Clinics Maintaining and Updating Equipment ~ 20% of Purchasing Price per year www.infrafrontier.eu Infrafrontier project – key objectives • Preparation to meet increasing demands for phenotyping and archiving – capacity building • Developing a business plan based on a sustainable funding concept • Identification of the most suitable legal form • Providing a strategic plan for the construction phase • Reaching a legal agreement between all partners www.infrafrontier.eu Key deliverables • WP2 – Strategy and Governance • WP3 – Legal Work • WP4 – Financial Work & Funding Implementation Preparatory Phase 2008 2009 Draft Strategic Plan WP2 2010 Update WP4 Finance WP3 Legal Work Strategic Plan Business Plan Legal status www.infrafrontier.eu 2011 MoU