1. MODO ( “Models Of Diabetes and Obesity”) Consortium Toni Vidal-Puig & Tony Coll

2. <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Obesity 2007 Diabetes 2007 Obesity, diabetes and related metabolic diseases are major and increasing threats to public health

3. <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Obesity 2007 Obesity 2010 Obesity, diabetes and related metabolic diseases are major and increasing threats to public health

4. Obesity, diabetes and related metabolic diseases are major and increasing threats to public health There remains a major unmet need for therapy and prevention

5. The MODO Consortium

6. OCDEM Mark McCarthy Anna Gloyn Patrick Rorsman Frederick Karpe Cecilia Lindgren University of Oxford Frances Ashcroft MRC Harwell Roger Cox Dundee Mike Ashford Calum Sutherland Rory McCrimmon Ewan Pearson MRC CORD Toni Vidal Puig Tony Coll + colleagues MRC Epidemiology Nick Wareham Ruth Loos MRC HNR Jules Griffin Imperial Guy Rutter MRC-CSC Dominic Withers University College, London Rachel Batterham The MODO Consortium

7. Specific aims To identify and develop specific therapeutic interventions. physiology pathology therapeutics To understand the molecular determinants of nutrient sensing and energy balance. To advance our understanding of B cell function and insulin action. To understand how alterations in theses pathways lead to metabolic disease

8. IMPC programme

9. data from existing models transcriptional profiling genetic association studies whole exome sequencing IMPC programme

10. data from existing models transcriptional profiling genetic association studies whole exome sequencing Secondary phenotyping

11. Murine phenotyping CambridgeLondon Dundee “Fine grained”, bespoke metabolic phenotyping Energy balance and body composition Whole body glucose homeostasis Histology Environmental influences Diet Activity Temperature Obesity associated metabolic complications

12. Metabolic disease - a disorder of whole organisms, not simply one system.

13. adipocyte biology pancreas Metabolic disease - a disorder of whole organisms, not simply one system. neuroendocrinologybrown adipose muscle behaviour liver gut

14. Rorsman Ashcroft Ashford Mechanistic cellular phenotyping - pancreas Rutter Withers Gloyn

15. Molecular phenotyping Expression profiling Pearson, Sutherland. McCarthy & colleagues Pharmocogenomics Withers, Yeo

16. Detailed human phenotyping Energy balance Functional imaging Fatty acid metabolism Body composition BatterhamKarpe Farooqi Savage Semple

17. For discussion Metabolic phenotypes are not necessarily acute or extreme – implications for primary screen Linking in with other programmes involving areas of expertise not historically allied to metabolic disease Data integration- within the consortium, within the whole IMPC Quality control during protocols and data acquisition Funding

18. OCDEM Mark McCarthy Anna Gloyn Patrick Rorsman Frederick Karpe Cecilia Lindgren University of Oxford Frances Ashcroft MRC Harwell Roger Cox Dundee Mike Ashford Calum Sutherland Rory McCrimmon Ewan Pearson MRC CORD Toni Vidal Puig Tony Coll + colleagues MRC Epidemiology Nick Wareham Ruth Loos MRC HNR Jules Griffin Imperial Guy Rutter MRC-CSC Dominic Withers University College, London Rachel Batterham The MODO Consortium