Bridging the gap from type 2 diabetes genetics to functional mechanisms of disease. (360G-Wellcome-095101_Z_10_Z)

£1,497,580

The overall objective of the Fellowship is to elucidate the functional mechanisms whereby genetic variants shown to influence Type 2 diabetes (T2D) predisposition exert their effects at the molecular, cellular and whole-body level. Initially, I will build on my existing research activity to explore the functional consequences of variants in three established T2D-susceptibility genes. I will: (a) determine the molecular mechanisms by which glucokinase promoter variants influence fasting gluco se levels and T2D-risk; (b) continue efforts to enumerate the full allelic spectrum of variants in the glucokinase regulatory protein gene, and to relate these variants to cellular, kinetic and clinical phenotypes; and (c) analyse human islets and rodent models to establish the mechanisms whereby variation in the adenylate cyclase 5 gene influences glucose homeostasis. In parallel, I will initiate functional characterisation of selected low frequency variants of moderate-to-large effect emer ging from ongoing high-throughput resequencing efforts in T2D. I will focus on variants which appear to mediate their T2D-risk through abrogation of islet function, using a combination of genetics, cellular and molecular biology and human physiology to reveal the mechanisms responsible. This work is expected to provide powerful insights into the pathophysiology of T2D that will support translational advances in disease management.

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Grant Details

Amount Awarded 1497580
Applicant Surname Gloyn
Approval Committee Basic Science Interview Committee
Award Date 2011-04-13T00:00:00+00:00
Financial Year 2010/11
Grant Programme: Title Senior Research Fellowship Basic
Internal ID 095101/Z/10/Z
Lead Applicant Prof Anna Gloyn
Partnership Value 1497580
Planned Dates: End Date 2016-06-30T00:00:00+00:00
Planned Dates: Start Date 2011-07-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Sir Peter Ratcliffe