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nfrafrontier European infrastructure for phenotyping archiving of model mammalian genomes dinator: Prof. Martin Hrabé de Angelis ect Office: Dr. Michael Raess, Dr. Ana de Castro holtz Zentrum München

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Page 1: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

InfrafrontierThe European infrastructure for phenotypingand archiving of model mammalian genomes

Coordinator: Prof. Martin Hrabé de AngelisProject Office: Dr. Michael Raess, Dr. Ana de CastroHelmholtz Zentrum München

Page 2: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

European Strategy Forum on Research Infrastructures

Page 3: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

ESFRI roadmap

• BBMRI – biobanking• EATRIS – translational research• ECRIN – clinical trials• ELIXIR – bioinformatics

• Infrafrontier – animal disease models

• INSTRUCT – structural biology

• EU-OPENSCREEN – chemical biology• BLS4 – high security labs• Euro-BioImaging - bioimaging• EMBRC – marine biology

First roadmapin 2006

First roadmapin 2006

First roadmapin 2006

35projects

Update inDec2008Update inDec2008Update inDec2008

+ 10projects

Page 4: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Grand Challenges

- Understand genetic and environmental impact on human health

- Develop novel strategies for diagnosis, prevention and therapies

Page 5: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Current Biology

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

Page 6: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Why mouse?

Mouse models achieve high impact

Publications on ‘Mouse Models’

Page 7: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Shortage on capacities and access:

Phenotyping (characterising mouse models)• Mouse ClinicsEUMODIC, Infrafrontier

Archiving and Dissemination of mice and data • RepositoriesEMMA, Infrafrontier

The challenge

Page 8: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Required capacities

European Phenotyping Capacities

'00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13

Mouse Lines / year

0

250

500

750

1000

1250

1500

1750

•Archiving and distribution

•Phenotyping

EMMA Submissions (total)

'02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13

Mouse Lines

0

1000

2000

3000

4000

5000

6000

7000

1500 p.a.

420 p.a.

EMMA Requests (total)

'02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13

Mouse Lines

0

1000

2000

3000

4000

5000

6000

7000

1500 p.a.

350 p.a.

Page 9: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Access to phenotyping data and mouse models

Infrafrontier

Phenomefrontier Archivefrontier

+ emerging centres + emerging centres

Infrafrontier: two main parts

SystemicPhenotyping

Archivefrontier/EMMAArchiving /Distribution

Access to phenotyping services, data and mouse models

Page 10: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Capacity building required!

Page 11: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Osteogenesis imperfectaA 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

Page 12: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

The German Mouse Clinic

www.mouseclinic.deNature Methods 2005, Nature Genetics 2005, Nature Genetics 2008, Cell 2009

Page 13: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

- 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

Mouse model for Osteogenesis imperfecta

Page 14: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

12 European Countries + Canada

Research Institutions + Funding Agencies

Infrafrontier partners

Page 15: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Infrafrontier partners

Page 16: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

InfrastructureLarge Project

Smaller Project

Page 17: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Very large Project:

International Mouse Phenotyping Consortium (IMPC)

Page 18: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Infrafrontier and IMPCKeep 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

Page 19: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Official start: 01 March 200836 months until: 28 February 2011

4.5 Mio € funding by the European Commission

Infrafrontier preparatory phase

www.infrafrontier.eu

Page 20: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Infrafrontier implementation

Page 21: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Infrafrontier implementation

Page 22: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Access to mouse resources and data

Page 23: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Operation Costs

Cohort Breeding23,000 – 30,000 € per line

Cohort Breeding23,000 – 30,000 € per line

Phenotyping15,000 – 20,000 € per line

Phenotyping15,000 – 20,000 € per line

Mouse Archiving3,500 – 4,400 € per line

Mouse Archiving3,500 – 4,400 € per line

Mouse Distribution1,100 – 2,100 € per line

Mouse Distribution1,100 – 2,100 € per line

ES Cell Distribution? € per line

ES Cell Distribution? € per line

User Fees1,100 – 1,700 €

User Fees1,100 – 1,700 €

User Fees500 –700 €

User Fees500 –700 €

User Feesto be developed

User Feesto be developed

Page 24: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

New mouse clinics and EMMA nodes

Established facilities

New facilities

Page 25: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Physical Infrastructure

Personnel

Operation

Technology Development

Integration of national & European funds

Nationalinfrastructure

funds

Nat

ion

al a

nd

Eu

rop

ean

Pro

ject

s

Funding Strategy

Page 26: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

MS

MS

MS

MS

MS

EuropeanCommission

CentralCoordinationMS

MS = Member State

Decentralised funding model

Page 27: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Governance Infrafrontier ERIC (Boards)

Page 28: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Governance Infrafrontier ERIC (Tasks)

Page 29: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

More Information ….

www.infraf

rontier.eu

Page 30: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

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 data-sharing plans at the outset of projects …”

Page 31: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

More Information ….

Coordinator:Prof. Dr. Martin Hrabé de [email protected]

Project Office:Dr. Michael RaessDr. Ana de [email protected]

Helmholtz Zentrum MünchenInstitute of Experimental GeneticsIngolstädter Landstrasse 185764 Neuherberg

Page 32: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

InfrafrontierThe European infrastructure for phenotypingand archiving of model mammalian genomes

Coordinator: Prof. Martin Hrabé de AngelisProject Office: Dr. Michael Raess, Dr. Ana de CastroHelmholtz Zentrum München

Page 33: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Scope of Activities

Page 34: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Constructing Required Capacities

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 €

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 €

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 €

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 €

Page 35: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Maintaining Capacities

Mouse Clinics

Maintaining and Updating Equipment~ 20% of Purchasing Price per year

Mouse Clinics

Maintaining and Updating Equipment~ 20% of Purchasing Price per year

EMMA Repository

Cryo-Archive (100 mouse lines):~ 10,000 € per year

Maintaining and Updating Equipment~ 10% of Purchasing Price per year

EMMA Repository

Cryo-Archive (100 mouse lines):~ 10,000 € per year

Maintaining and Updating Equipment~ 10% of Purchasing Price per year

Page 36: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

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

Page 37: Infrafrontier The European infrastructure for phenotyping and archiving of model mammalian genomes Coordinator: Prof. Martin Hrabé de Angelis Project Office:

www.infrafrontier.eu

Implementation

Preparatory Phase

Key deliverables

• WP2 – Strategy and Governance• WP3 – Legal Work• WP4 – Financial Work & Funding

2008 2009 2010 2011

WP2

WP3 Legal Work

MoU

Strategic PlanDraft Strategic Plan

WP4 FinanceBusiness Plan

Legal status

Update