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

<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

<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

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

The MODO Consortium

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

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

IMPC programme

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

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

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

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

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

Rorsman Ashcroft Ashford Mechanistic cellular phenotyping - pancreas Rutter Withers Gloyn

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

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

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

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