Sorting proinsulin into secretory vesicles

Summary

Reduction in glucose-stimulated mature insulin secretion and increased constitutive and regulated secretion of proinsulin are characteristics of β-cell failure. This may be due to defects in the initial sorting of proinsulin into secretory vesicles and processing of proinsulin into mature insulin. The exact mechanisms that are responsible for sorting of proinsulin at the trans-Golgi network (TGN) are not fully defined. In this project we aim to investigate if the principal component of a novel cargo sorting pathway is involved in proinsulin trafficking and packaging into secretory vesicles in β-cells.

Supervisor(s)

Dr Melkam Kebede

Research Location

School of Life and Environmental Sciences

Program Type

Masters/PHD

Synopsis

The exact mechanisms that are responsible for sorting of proinsulin at the trans-Golgi network are not fully defined. In this project we will investigate if the principal components of a novel cargo sorting pathway involving a soluble Golgi resident protein is involved in proinsulin trafficking and packaging into secretory granules. Insights from this work could lead to the development of novel therapeutic approaches aimed at efficient packaging and processing of proinsulin into mature insulin and increase availability of mature insulin for secretion.

Additional Information

HDR Inherent Requirements

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:

- Confidential disclosure and registration of a disability that may hinder your performance in your degree;
- Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
- Ability to perform independently and/or with minimal supervision;
- Ability to undertake certain physical tasks (e.g. heavy lifting);
- Ability to undertake observatory, sensory and communication tasks;
- Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
- Ability to work in confined spaces or at heights;
- Ability to operate heavy machinery (e.g. farming equipment);
- Hold or acquire an Australian driver’s licence;
- Hold a current scuba diving license;
- Hold a current Working with Children Check;
- Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

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Keywords

islet, insulin secretion, insulin granules, beta-cell failure, Type 2 diabetes, confocal microscopy, mass spectrometry, trans Golgi network, cargo sorting, proinsulin, vesicles, trafficking

Opportunity ID

The opportunity ID for this research opportunity is: 2490

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