Characterisation of the role of perilipin in the molecular regulation of triglyceride hydrolysis (360G-Wellcome-091551_Z_10_A)
My project has four themes: 1) Characterising the phenotype and molecular properties of two novel forms of lipodystrophy due to mutations in two lipid droplet proteins, perilipin and CIDEC. Perilipin s biological role is well documented so I will define the human phenotype associated with the mutations and characterise the biological properties of the mutants. The biological function of CIDEC is poorly understood, so I will characterise the mutant and explore the protein s biology including d etermining its precise localisation, its structure and identifying interacting proteins. 2) To use patients with genetically defined forms of lipodystrophy to explore questions relating to more common diseases - a) To understand the mechanisms of adaptive thermogenesis in lipodystrophy using humans and animal models. b) To identify the major sources of fatty acids responsible for fatty liver and dyslipidaemia? c) To establish if mitochondrial dysfunction, a feature of T2DM, is a cause or conseq uence of insulin resistance? 3) To identify novel genetic causes of lipodystrophy using next generation sequencing platforms. 4) To establish protocols for adipocyte differentiation of induced pluripotent stem cells. These cells will be invaluable tools for characterising the consequences of novel and unidentified forms of lipodystrophy and, ultimately for therapeutic replacement strategies.
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Grant Details
Amount Awarded | 101737 |
Applicant Surname | Savage |
Approval Committee | Science Enhancement Committee |
Award Date | 2012-09-06T00:00:00+00:00 |
Financial Year | 2011/12 |
Grant Programme: Title | Enhancement |
Internal ID | 091551/Z/10/A |
Lead Applicant | Prof David Savage |
Partnership Value | 101737 |
Planned Dates: End Date | 2014-10-31T00:00:00+00:00 |
Planned Dates: Start Date | 2012-11-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |