The Role of Senescence in Vascular Function and Disease

Summary

The research opportunities available involve different projects centred around the role of senescence in disease. Projects include:

1. understanding the signalling pathways and gene regulation in senescence
2. Structure and function of a novel gene involved in senescence
3. Senescence as a major regulator of disease (including ageing, cancer, arthritis, atherosclerosis and other chronic inflammatory)

Supervisor(s)

Professor Jennifer Gamble

Research Location

Camperdown - Centenary Institute

Program Type

Masters/PHD

Synopsis

The laboratory has recently discovered a novel gene, now called SENEX, which provides a unique gatekeeper function in endothelial cells. SENEX levels regulate major states of the endothelium, such as cell survival, apoptosis, and induction of senescence. Thus, SENEX is proposed to act as a fulcrum for the modulation of endothelial cell function. The initial description of the function of SENEX has been published (Coleman et al Blood 2010 Nov 11; 116(19), 4016-4024). This work formed the basis for a PhD for P. Coleman.
SENEX is regulated in disease, however the impact of this regulation on the disease progression is not understood. We have developed mutant mice for SENEX and these will be used to dissect the role of SENEX in diseases where there is dysfunction of the endothelium and chronic inflammation is a hallmark (such as atherosclerosis, tumour growth, arthritis, ageing). SENEX is also seen in other cell types such as macrophages and mast cells and the role in the function of these cells in being investigated.
The signalling pathways which result in perturbation of endothelial cell function and which may result in changes to SENEX expression are being investigated. Critical to an understanding of these pathways is studies to identify the localisation of SENEX in the cell, its association with critical signalling molecules and the structure of the SENEX protein which is responsible for its mode of action.

Additional Information

The laboratory is supported through the NHMRC Program Grant system and through grants from the National Heart Foundation and ARC. The laboratory includes 5 post doctoral fellows, 4 research assistants, two PhD students and one visiting scientist. Positions are available for a further two PhD students and two Honours students.

Keywords

vasculature including endothelial cells and smooth muscle cells, macrophage and mast cell functions, inflammation, angiogenesis, senescence, Cancer, atherosclerosis, arthritis, Ageing

Opportunity ID

The opportunity ID for this research opportunity is: 1429

Other opportunities with Professor Jennifer Gamble

• Regulation of the Vascular System: Role of the Endothelium
• The Role of microRNAs in Vascular Function and Disease
• Control of tumour growth by oncogene-induced senescence