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MODO ( “ M odels O f D iabetes and O besity”) Consortium. Toni Vidal- Puig & Tony Coll. Obesity, diabetes and related metabolic diseases are major and increasing threats to public health. <10% 10%–14% 15%–19% 20%–24% 25%–29%
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MODO ( “Models Of Diabetes and Obesity”) Consortium Toni Vidal-Puig & Tony Coll
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 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 2010 Obesity 2007
Obesity, diabetes and related metabolic diseases are major and increasing threats to public health There remains a major unmet need for therapy and prevention
Dundee Mike Ashford Calum Sutherland Rory McCrimmon Ewan Pearson OCDEM Mark McCarthy Anna Gloyn Patrick Rorsman Frederick Karpe Cecilia Lindgren MRC CORD Toni Vidal Puig Tony Coll + colleagues MRC Epidemiology Nick Wareham Ruth Loos University of Oxford Frances Ashcroft MRC HNR Jules Griffin Imperial Guy Rutter MRC Harwell Roger Cox MRC-CSC Dominic Withers University College, London Rachel Batterham The MODO Consortium
Specific aims • To understand the molecular determinants of nutrient sensing and energy balance. To advance our understanding of B cell function and insulin action. physiology To understand how alterations in theses pathways lead to metabolic disease pathology • To identify and develop specific therapeutic interventions. therapeutics
transcriptional profiling data from existing models genetic association studies whole exome sequencing IMPC programme
transcriptional profiling data from existing models genetic association studies whole exome sequencing Secondary phenotyping
Murinephenotyping Dundee Cambridge London “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.
Metabolic disease - a disorder of whole organisms, not simply one system. neuroendocrinology brown adipose gut muscle behaviour pancreas liver adipocyte biology
Mechanistic cellular phenotyping - pancreas Ashcroft Rutter Withers Ashford Rorsman Gloyn
Molecular phenotyping Expression profiling Pharmocogenomics Pearson, Sutherland. McCarthy & colleagues Withers, Yeo
Detailed human phenotyping Energy balance Body composition Functional imaging Fatty acid metabolism BatterhamKarpeFarooqi 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
Dundee Mike Ashford Calum Sutherland Rory McCrimmon Ewan Pearson OCDEM Mark McCarthy Anna Gloyn Patrick Rorsman Frederick Karpe Cecilia Lindgren MRC CORD Toni Vidal Puig Tony Coll + colleagues MRC Epidemiology Nick Wareham Ruth Loos University of Oxford Frances Ashcroft MRC HNR Jules Griffin Imperial Guy Rutter MRC Harwell Roger Cox MRC-CSC Dominic Withers University College, London Rachel Batterham The MODO Consortium