Diabetes and beta-cell gene expression

Summary

Diabetes develops when the insulin secreting beta-cells in the pancreas can no longer release enough insulin to control blood glucose concentrations. This often occurs in the setting of insulin resistance, for example with obesity, lack of exercise, or with increased genetic risk in families with high risk of diabetes. We now have an exciting tool called TRAP (Translating Ribosome Affinity Purification), which will allow us to study short-term changes in beta-cell gene expression in vivo. This project will utilize this model to examine the effects of various beta-cell stresses on gene expression and development of diabetes.

Supervisor(s)

Professor Jenny Gunton

Research Location

Westmead - Westmead Institute for Medical Research

Program Type

PHD

Synopsis

This project will use beta-cell TRAP mice. TRAP is translating ribosome affinity purification. These mice can crossed with other mice in our lab to study the effects of various gene deletions in beta-cells, for example vitamin D receptor to enable us to study the effects of vitamin D on beta-cells. The technique can be used with a wide variety of questions, depending on the student's interest, and we are keen to work with an interested student to develop a project if it falls within the lab's interest in diabetes and transcription factors.

Additional Information

Westmead Institute for Medical Research has a ‘top-up' award program for students who are successful in obtaining a scholarship (e.g. Research Training Award).

Some papers from the lab in the area of beta-cell biology and vitamin D are below.

Sherman MH, Yu RT, Engle DD, Ding N, Atkins AR, Tiriac H, Collisson EA, Connor F, Van Dyke T, Kozlov S, Martin P, Tseng TW, Dawson DW, Donahue TR, Masamune A, Shimosegawa T, Apte MV, Wilson JS, Ng B, Lau SL, Gunton JE, Wahl GM, Hunter T, Drebin JA, O'Dwyer PJ, Liddle C, Tuveson
 
DA, Downes M, Evans RM. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell. 2014 Sep 25;159(1):80-93. Lalwani A, Lau SM, Gunton JE. Deletion of ARNT (Aryl hydrocarbon receptor nuclear translocator) in β-cells causes islet transplant failure with impaired β-cell function. PLoS One. 2014 May 30;9(5):e98435.

Lau SM, Cha KM, Karunatillake A, Stokes RA, Cheng K, McLean M, Cheung NW,
Gonzalez FJ, Gunton JE. Beta-cell ARNT is required for normal glucose tolerance
in murine pregnancy. PLoS One. 2013 Oct 24;8(10):e77419.

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Keywords

Beta-cell, diabetes, glucose intolerance, type 1 diabetes, Type 2 diabetes, gestational diabetes, Pregnancy, Insulin resistance, Vitamin D, Vitamin D Receptor, PCR, gene expression, RNA-sequencing, TRAP, translating ribosome affinity purification

Opportunity ID

The opportunity ID for this research opportunity is: 2251

Other opportunities with Professor Jenny Gunton