June 2017: post-doc in stem cell research
We are recruiting a post doc fellow to work in the Charles Perkins Centre. This is a 4 year fellowship, funded by a generous donation from John and Anne Chong. The project will differentiate hiPSCs to optimise their glucose sensitivity and insulin secretion and will be conducted as part of a larger team that aims to develop capsules to house insulin-secreting cells and treat type 1 diabetes.
The position is advertised here: University of Sydney website . Please contact Peter Thorn to discuss details.
Project 1 Understanding the structure and functions that control insulin secretion within islets. Our discovery that beta cells secrete insulin via a synaptic-like connection with blood vessels in the islet challenges accepted models of insulin secretion. Ongoing work in the lab is showing the synapse changes in type 2 diabetes, suggesting it may be significant in disease. The next step in this work is to identify the fundamental mechanisms that establish the synapse.
This project will use electron and light microscopy in rodent and human islets to identify the potential components that position the synapse. Molecular methods and transgenic animal approaches will then test the significance of these candidates in the structural development and maintenance of the synapse and in the functional control of insulin secretion. The PhD student will drive their own project and also contribute to research as part of a wider team that includes labs in Sydney and Toronto.
Project 2 Understanding the defects in insulin secretion that occur in disease. This project will engage in our current focus on prediabetes. Our ongoing work is showing that the pancreatic beta cells actively participate in the enhanced insulin secretion in prediabetes.
This project will use a range of microscopy methods to study a mouse model of type 2 diabetes as well as human tissue from diabetic patients. The initial aim is to understand the functional changes that occur in beta cells that lead to enhanced secretion. This will then be expanded to investigate the mechanisms that underlie the subsequent loss of secretion that occurs as the disease progresses. The PhD student will work as part of a wider team that includes labs in Sydney and Florida.
Project 3 Refining cell-based therapies to cure diabetes. The most promising route for a cure for type 1 diabetes is the use of insulin-secreting cells to replace those that have died.
This project will use human pluripotent stem cells and use techniques to grow insulin-secreting cells. Work in other labs has followed this method but the cells secrete little insulin and do not respond properly to glucose. The PhD student will build on the experience and data from our lab that shows how beta cells behave in native islets and aim to recapitulate this by refining the conditions of cell culture. The PhD student will work with other members of the lab in Sydney and collaborate with stem cell labs in Queensland.
The lab welcomes approaches from well qualified, dedicated researchers and we can explore possible funding opportunities.
Project 1. Understanding how the pancreatic beta cell synapse controls insulin secretion. Our discovery that beta cells secrete insulin via a synaptic-like connection with blood vessels in the islet challenges accepted models of insulin secretion. Ongoing work in the lab is showing the synapse changes in type 2 diabetes, suggesting it may be significant in disease. The next step in this work is to prove that functional interactions in the synapse have significance for the control of insulin secretion. To this end, in this project we will stain for the key proteins in the beta cell synapse and use super resolution microscopy to determine their relative position. This approach will be complemented by live-cell two-photon imaging of insulin secretion. The outcomes of the project will be significant for both understanding and treatment of diabetes.
Project 2. Are pancreatic beta cells damaged in prediabetes? Prediabetes is a recognised as a medical condition where blood sugar levels are higher than normal but not in the diabetic range. It affects around 1/6 of the Australian population and is known to be a significant risk factor in developing type 2 diabetes. However, whether it is a disease and whether it should be treated is controversial. A step towards resolving the issue would be to show that fundamental changes are occurring in the regulation of insulin secretion. To this end, this project will study insulin secretion from prediabetic and diabetic pancreatic islets. Our preliminary data indicates that prediabetes is associated with pathological increases in insulin secretion and in this project these will be defined. Furthermore, we plan experiments to test the efficacy of a range of treatments.
find us in the 2016 Honours in Physiology booklet ->