modo ( “ m odels o f d iabetes and o besity”) consortium
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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.TRANSCRIPT
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MODO ( “Models Of Diabetes and Obesity”) Consortium
Toni Vidal-Puig & Tony Coll
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<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
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<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
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Obesity, diabetes and related metabolic diseases are major and increasing threats to public health
There remains a major unmet need for therapy and prevention
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The MODO Consortium
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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
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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
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data from existingmodels
transcriptionalprofiling
geneticassociation studies
whole exomesequencing
IMPC programme
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data from existingmodels
transcriptionalprofiling
geneticassociation studies
whole exomesequencing
Secondary phenotyping
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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
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Metabolic disease- a disorder of whole organisms, not simply one system.
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adipocyte biology
pancreas
Metabolic disease- a disorder of whole organisms, not simply one system.
neuroendocrinology brown adipose
muscle
behaviour
liver
gut
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Rorsman
Ashcroft
Ashford
Mechanistic cellular phenotyping - pancreas
Rutter
Withers
Gloyn
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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
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Detailed human phenotypingEnergy balance Functional imaging
Fatty acid metabolism
Body composition
Batterham Karpe Farooqi Savage Semple
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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
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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