modo ( “models of diabetes and obesity”) consortium toni vidal-puig & tony coll
TRANSCRIPT
<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 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
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 phenotyping
Energy balance and body
composition
Whole body glucose homeostasis
Histology
Environmental influencesDiet Activity Temperature
Obesity associated metabolic complications
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)
No
rma
lize
d s
ign
al i
nte
nsi
ty (
FA
ST
)
10 100 1000 1e4
10
100
1000
1e4
Normalized signal intensity (FED)
No
rma
lize
d s
ign
al i
nte
nsi
ty (
LE
PT
IN)
Pharmocogenomics
Withers, Yeo
Detailed human phenotyping
Energy 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 Batterham
The MODO Consortium