The Role of microRNAs in Vascular Function and Disease

Summary

Identification of microRNAs which are important in endothelial cell functions. These are: angiogenesis, permeability, senescence and differentiation (the project will be targeted to a selected aspect)The project will define the targets and mechanism of action of the microRNAs in the endothelial cell function.

The project will determine whether the microRNAs influence disease using animal models.

Supervisor(s)

Professor Jennifer Gamble

Research Location

Camperdown - Centenary Institute

Program Type

Masters/PHD

Synopsis

MiRNAs are a highly conserved class of endogenous small non-coding RNAs (20-25 nucleotides) which regulate genes at the post-transcriptional stage of expression. They have been implicated in diverse cellular processes such as development, proliferation, differentiation and apoptosis. In recent times there has been a focus on the role of miRNAs in disease, based primarily on their ability to influence major genetic programmes and modulate scores, if not hundreds, of target genes. To date approximately 800 human miRNAs have been identified and using bioinformatic target predictions they are estimated to regulate more than 30% of all protein-coding genes. MiRNAs have been shown to be dysregulated and contribute to the initiation and development of many diseases. The alteration of the miRNAs can be a result of genetic or epigenetic alterations effecting expression or in mutations within the seed sequences which effect target binding.
Since angiogenesis, senescence, differentiation and changes in permeability all involve major phenotypic alterations in the endothelial cells of the vasculature, we reasoned that miRNAs will exert another layer of control over these processes. We have iniated studies into angiogenesis and have identified a panel of miRNAs which are regulated during angiogenesis and have confirmed that they target key molecules in angiogenesis. Further we know that ectopic regulation of these miRNAs can influence the extent of angiogenesis. Thus we are now able to determine whether these miRNAs influence diseases such as tumour growth, wound healing and arthritis, all of which involve an angiogenic component.
Using similar technology we wish to investigate miRNAs which regulate permeability, senescence and endothelial cell differentiation from progenitor cells.

Additional Information

The laboratory is supported through the NH&MRC Program Grant system and through grants from the National Heart Foundation and ARC. The laboratory includes 5 post-doctoral fellows, 4 research assistants, 2 PhD students and 1 visiting scientist.

Positions are available for a further three PhD students and two Honours students.

Keywords

microRNA, vasculature including endothelial cells and smooth muscle cells, inflammation, angiogenesis, Cancer, permeability

Opportunity ID

The opportunity ID for this research opportunity is: 1428

Other opportunities with Professor Jennifer Gamble

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