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Student research project

Supervisor(s): Morag Young

Project summary

The global importance of addressing cardiovascular disease and hypertension cannot be overestimated; this field needs new insights and novel strategies.

The mineralocorticoid receptor (MR) is classically associated with the regulation of sodium, potassium, fluid balance and blood pressure control. It is also present in various non-epithelial cell types including cardiac myocytes, vascular smooth muscle cells, brain cells and immune cells such as macrophages. In these cells, the actions of the MR are not completely characterised but in many cases do not relate to salt or fluid regulation. At present, the cascade of events leading to MR activation and how MR activation results in inflammation and fibrosis are not clearly defined. In animal models, cardiac fibrosis is exacerbated by mineralocorticoid/salt administration but attenuated by receptor blockade and absent in mice specifically lacking cardiac myocyte MR or macrophage MR. Previous data from this laboratory demonstrate a critical role for MR signalling in the monocyte/macrophage lineage, a cell type in which the role of MR signalling is poorly defined.

The recent identification of the cardio-protective effects of macrophage-specific deletion of the MR is an exciting advance in our understanding of disease processes and highlights new therapeutic targets that could lead to new treatments for the treatment of cardiac failure and hypertension that are specifically designed for macrophages. The goal of this project is to identify novel pathways using novel proteomic and genomic screening technologies and to define and characterise these pathways using human cell lines and primary cells and clinical samples where possible. Bioinformatic analyses of large clinical databases will also be involved. In this way, we hope to identify novel mechanisms of heart disease, determine the optimal way to treat patients and avoid the serious side effects of current treatments.

Related methods, skills or technologies

This project is suitable for a Masters, Honours or PhD student and will involve the application of various techniques including tissue culture, cytokine assays, RTPCR, western blot, bioinformatics and FACS.

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