ProfessorJennifer Gamble

Project Opportunities

Title: Understanding ageing of the endothelium

Summary of opportunity:

The investigations are focussed on identifying the biological and molecular changes that occur when endothelial cells undergo senescence (ageing) and the impact on disease such as diabetes, cancer, heart disease and atherosclerosis.

Opportunity synopsis:

The technologies utilised encompass, gene arrays of aged cells and tissues, molecular dissection of signalling pathways, biochemical analysis of protein structure and functions, in vitro assays of cellular function, state-of-the art imaging of cellular structures and protein localisation, animal models using genetically mutant mice and disease models and zebrafish for vascular analysis.

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Project Opportunities

Title: Diseases of the Aorta

Summary of opportunity:

The causes of sporadic thoracic aortic aneurysms are not understood but the consequences of this disease can be catastrophic. We have developed an animal model of disease and this together with human tissue will be used to identify the molecular determinants (mRNA, microRNA, epigenetic) of disease progression by analysis of the endothelial cell and smooth muscle cell compartments.

The importance of the identified genes will be confirmed through analysis of human disease, performed in collaboration with Prof Richmond Jeremy and Prof Paul Bannon, Royal Prince Alfred Hospital.

Opportunity synopsis:

Technologies to be used include animal and in vitro models of disease, cell extraction and isolation, gene arrays probing gene and miRNA expression, molecular analysis of signalling pathways, expression analysis in extensive clinical and archival human material, iPS cell isolation and analysis.

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Project Opportunities

Title: MicroRNAs in disease

Summary of opportunity:

Regulation of the endothelial cell barrier integrity is critical in inducing new blood vessel formation (angiogenesis), in developing an inflammatory response and importantly in resolving or inhibiting the response. We have shown that microRNAs are essential in these events and moreover are altered when there is chronic unresolved disease. Our investigations are into determining the important molecular targets of the microRNAs, understanding the dysregulation of these microRNAs in disease where endothelial cell angiogenesis and permeability are major contributing factors and developing these microRNAs or their inhibitors as potential therapeutics.

Opportunity synopsis:

Technologies include, molecular studies of target expression, genetic manipulation of the microRNAs, in vitro models of endothelial cell function, state-of-the art imaging, animal models of disease and zebrafish models for vascular development.

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Project Opportunities

Title: Understanding the role of novel genes in disease

Summary of opportunity:

From mRNA arrays we have identified a number of ‘novel’ genes that influence tissue function. Our studies are investigating the biochemical basis for the mechanism of action, the structural basis for function and the role of these genes in disease. Thus far we have identified genes with major effects on obesity, liver disease, liver fibrosis and solid tumour growth.

Opportunity synopsis:

Technologies include state-of-the art imaging, biochemical analysis of signalling pathways, molecular analysis for protein structure, in vitro cell based models, animal models of disease using normal and mutant mice, generation of unique mutant mice.

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Project Opportunities

Title: Ageing Blood Vessels

Summary of opportunity:

Techniques: high resolution imaging, use of new imaging platforms such as ImageStream, molecular biology, tissue culture, in vitro models of disease, flow cytometry, establishment of new technologies essential to the project (where feasible).

Opportunity synopsis:

Age is the greatest risk factor for disease. Furthermore, blood vessel dysfunction is one of the major hallmarks of chronic age-related disease. We want to understand cellular ageing and in particular how ageing impacts the function of the cells of the blood vessels, namely endothelial cells, pericytes.
Endothelial cells form the lining of blood vessels and they maintain the anti-inflammatory, anti-thrombotic and selectively permeable nature of blood vessels. Pericytes wrap around the endothelial cells and their intimate contact is essential to maintain the function of blood vessels to control inflammation, thrombosis and blood pressure.
We are investigating the molecular, biological and metabolic changes that are induced in ageing endothelial cells and pericytes and how these changes could predispose us to diseases of the age.

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Project Opportunities

Title: Alzheimer's Disease and Blood Vessels

Summary of opportunity:

Techniques: single cell RNAsequencing and gene expression analysis, high resolution imaging, molecular biology, tissue culture, in vitro models of disease, flow cytometry, some animal models of disease (but not all projects require animal work).

Opportunity synopsis:

AD is an age-related neurodegenerative disease that progressively affects brain function. AD is the most common form of dementia, which is the 2nd leading cause of death in Australia. In 2019 there were approximately 500,000 Australians with dementia, of which about 70% suffer from AD.
One of the newer concepts in the understanding of Alzheimer's is that changes in the brain vasculature are an early major contributing factor to the pathogenesis. The significant change seen early in AD is in the breakdown in the blood-brain barrier, where the vessels become leaky and this occurs before the formation of the classic features of Alzheimer's pathology, the plaques and the tau tangles.
Our research is directed to understanding the molecular changes that occur in the blood vessels that result in the progression of Alzheimer's. Further, we are developing new drugs that specifically target the altered cells of the vasculature in the hope that these may retard or reverse the progression of AD.

----------Current Research Projects----------

The projects available for PhD, Masters and Honours students are:

the role of the aged vasculature in the initiation and development of disease

It has been said ' you are only as old as your blood vessels' . It is now appreciated that age is the greatest risk factor for disease. Thus the projests are focussed on understanding the impact of age on endothelial cell function and hence on disease. Our disease focus are:

Alzheimer's Disease,since one of the early changes in the brain of AD is the disruption of the blood brain barrier and in particular in the loss of the endothelial cell barrier integrity. This project will help us understand the consequences of the ageing process to the inflammatory response that is occuring in the brain. It will expose novel drug targets in the treatment of Alzheimer's Disease.

Calcific aortic valve disease (CAVD).

CAVD is the most common valvular heart disease in developed countries and the incidence of the disease increases with age.At present there are no drug therapies available for this disease and we have a limited understanding of the underlying molecular and cellular mechanisms of calcification that may help in the development of therapeutics. This project will investigate the role of the aged endothelium in CAVD.

Technologies.

Tissue culture assays, molecular and cellualr biology, high resolution imaging, animal models of disease, single cell RNAsequencing.