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Garvan Institute of Medical Research. Tel: 9295 8210
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Signal Transduction, Vesicle Transport and Metabolic Disease
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Understanding the molecular regulation of fuel metabolism has become one of the most exciting challenges in biology. New developments have revealed a complex communication between major metabolic regulatory organs (muscle, liver, adipose tissue and pancreas), the immune system and the brain. This network controls appetite, whole body insulin sensitivity and body weight and disruptions in the interplay between these systems contributes to an expanding family of metabolic disease including Type 2 Diabetes and obesity.
My laboratory is interested in dissecting this metabolic circuitry at a fundamental level. In addition to the standard tools of molecular cell biology we are utilising a range of evolving technologies. These include RNA silencing techniques for suppressing gene expression, in vitro assays that allow precise measurement of cell biological targets and high resolution imaging techniques such as Total Internal Reflection Fluorescence Microscopy, which can be used to measure molecular changes within defined regions in individual cells.
Honours students may select from projects within the following areas:
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Project 1: Vesicle transport
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Many of the processes in this metabolic circuit involve regulated secretion. Examples include insulin secretion from the pancreas, insulin-stimulated movement of the glucose transporter GLUT4 in muscle and fat cells and leptin secretion from adipocytes. Each of these processes utilise homologous sets of proteins that regulate protein sorting as well as vesicle budding, docking and fusion. Our emphasis is to delineate the function of such molecules and to identify the unique modes of regulation that distinguish different transport reactions.
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Project 2: Signal transduction
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Much evidence points to a defect in the insulin signal transduction cascade in Type 2 Diabetes. The PI 3’ kinase/Akt pathway which is activated following tyrosine phosphorylation of the scaffold protein IRS1 plays a pivotal role in many of insulin’s actions. Our laboratory aims to identify new downstream targets of Akt in muscle and fat cells and to characterise the role of serine/threonine phosphorylation of IRS1 in the development of insulin resistance.
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Selected Reference (Available on request)
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Bryant, NJ, Govers, R. and James, DE Regulated transport of the glucose transporter GLUT4. Nat Rev Mol Cell Biol. 3, 267-77, 2002.
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