Student research project
Supervisor(s): Professor David Kaye and Dr Francine Marques
Project summary
The focus of this project is to determine the cardiovascular phenotype of G-coupled protein receptor (GPRCs) knockout mouse models such as Gpr109 and double knockout Gpr41/43, and their relevance in the dietary prevention of high blood pressure and heart failure through the gut microbiota.
Heart failure is a common progressive disease and a major cause of death. After age, the most important cardiovascular risk factor for heart failure is high blood pressure (i.e. hypertension) which is typically associated with cardiac remodelling. Patients with heart failure have scarring of the heart with the accumulation of fibroblasts and extracellular matrix, leading to stiffness and, thus, a decrease in pumping function. While epidemiological studies show that obesity and a high fat and high sodium intake are clear contributors to hypertension and heart failure, it is starting to emerge that other dietary components such as fibre might also modulate cardiovascular risk factors. The mechanism, however, is not known. Consumption of a diet high in fibre increases gut microbiota populations that, through fermentation, generate short chain fatty acids (SCFAs), which have a protective role in experimental models of inflammatory diseases.
We have recently found that dietary manipulation with fibre or acetate can prevent the development of high blood pressure and heart failure in a model of disease. This may happen through G-protein coupled receptors such as GPR43, GPR41 and GPR109, key receptors for SCFA in the gut and immune cells. The overall aim of this project is to determine the effect of these receptors in high blood pressure and heart failure. This will be achieved by establishing the cardiovascular phenotype of Gpr109 and Gpr41/43 double knockout mice, followed by treating these mice the different types of diet and inducing the development of cardiovascular disease. We hypothesize that mice lacking these receptors will not respond to dietary fibre or SCFA intake.
This project will form the basis for the development of new therapies focused on the prevention and treatment of serious cardiovascular diseases such as heart failure.
It is suitable for a PhD or Honours student and will involve applying various skills and techniques, including:
- preclinical procedures
- next-generation sequencing (RNA-sequencing) and bioinformatics
- flowcytometry
- molecular biology
- statistics.
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