MODO ( “ M odels O f D iabetes and O besity”) Consortium

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

OCDEMMark McCarthy

Anna GloynPatrick RorsmanFrederick KarpeCecilia Lindgren

University of OxfordFrances Ashcroft

MRC HarwellRoger Cox

DundeeMike Ashford Calum SutherlandRory McCrimmon Ewan Pearson

MRC CORDToni Vidal Puig Tony Coll

+ colleagues

MRC EpidemiologyNick Wareham Ruth Loos

MRC HNRJules Griffin

ImperialGuy Rutter

MRC-CSCDominic Withers

University College, LondonRachel BatterhamThe 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 existingmodels

transcriptionalprofiling

geneticassociation studies

whole exomesequencing

IMPC programme

data from existingmodels

transcriptionalprofiling

geneticassociation studies

whole exomesequencing

Secondary phenotyping

Murine phenotypingCambridge London Dundee

“Fine grained” , bespoke metabolic phenotypingEnergy balance

and body composition

Whole body glucose homeostasis

Histology

Environmental influencesDiet 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.

neuroendocrinology brown adipose

muscle

behaviour

liver

gut

Rorsman

Ashcroft

Ashford

Mechanistic cellular phenotyping - pancreas

Rutter

Withers

Gloyn

Molecular phenotyping

Expression profiling

Pearson, Sutherland. McCarthy& colleagues

Down in fasting

Up in fasting

10 100 1000 1e4

10

100

1000

1e4

Normalized signal intensity (FED)

Nor

mal

ized

sig

nal in

tens

ity (F

AST

)

10 100 1000 1e4

10

100

1000

1e4

Normalized signal intensity (FED)

Nor

mal

ized

sig

nal in

tens

ity (L

EPT

IN)

Pharmocogenomics

Withers, Yeo

Detailed human phenotypingEnergy balance Functional imaging

Fatty acid metabolism

Body composition

Batterham Karpe 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

OCDEMMark McCarthy

Anna GloynPatrick RorsmanFrederick KarpeCecilia Lindgren

University of OxfordFrances Ashcroft

MRC HarwellRoger Cox

DundeeMike Ashford Calum SutherlandRory McCrimmon Ewan Pearson

MRC CORDToni Vidal Puig Tony Coll

+ colleagues

MRC EpidemiologyNick Wareham Ruth Loos

MRC HNRJules Griffin

ImperialGuy Rutter

MRC-CSCDominic Withers

University College, LondonRachel BatterhamThe MODO Consortium