| Title | Regulation of cellular coupling in the healthy and diseased heart |
|---|---|
| Supervisors | Susan Currie Gwyn Gould |
| Research Area | Cardiovascular and Metabolic Disease Cell Biology |
| Description | The heart is composed of a number of cell types including cardiomyocytes, fibroblasts, endothelial cells and vascular smooth muscle cells. Despite the key role played by cardiomyocytes in contraction, fibroblasts outnumber these cells, and play a crucial part in maintaining healthy cardiac function. In the diseased heart, significant remodelling occurs in response to a variety of stressors and cardiac fibroblasts become activated, resulting in differentiation to myofibroblasts. These myofibroblasts can influence both structural and contractile parameters leading to global cardiac dysregulation. One of the routes by which both fibroblasts and myofibroblasts may communicate with other cell types is via release of high levels of exocytic vesicles. These vesicles are known to secrete many factors, including proinflammatory and pro-fibrotic signals and, as such, may be crucial to the structural and contractile dysregulation that occurs during disease. Using a combination of ex vivo and in vitro approaches, this project will examine how fibroblasts and myofibroblasts communicate and interact with cardiomyocytes. The project will consider how one cell type can influence the other, either via direct interaction or through modulation via factors that are secreted from the cells. Our work will focus on the trans-cellular delivery of signalling systems and, importantly, will examine the impact of disease on inter-cellular communication. The project will use a cell-based model to mimic the cellular changes that occur in the diseased heart and will examine a combination of primary adult cardiac cells and induced pluripotent stem-cell-derived cardiomyocytes in co-culture systems. The overall aim will be to identify key factors that are crucial in modulating cell-cell communication in health and disease. |
| Techniques Used | Cell Culture Langendorff Perfusion Protein analysis Imaging Genome Editing/siRNA approaches |
| References | Myocyte-Fibroblast communication in cardiac fibrosis and arrthymias: mechanisms and model systems. J Mol Cell Cardiol. 2016 May; 94: 22–31. Extracellular vesicles: a new communication paradigm? Nature Reviews Molecular Cell Biology volume 20, pages 509–510 (2019) |
| Conditions | Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a Biological Science in addition to receipt of satisfactory references and an IELTS score of 6.5 where appropriate. |
| Bench Fee | Running costs of £12000 p.a. will be associated with this project in addition to University tuition fees. |
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