Molecular mechanisms controlling cardiac fibroblast proliferation during cardiac fibrosis

Applicants are invited for a new self-funded PhD studentship to study the molecular mechanisms of cardiac fibrosis.

Myocardial fibrosis is a significant global health problem associated with nearly all forms of heart disease. Cardiac fibroblasts comprise an essential cell type in the heart that is responsible for the homeostasis of the extracellular matrix. However, upon injury, these cells transform to a myofibroblast phenotype and begin to proliferate. This results in excessive deposition of extracellular matrix (ECM) proteins, which increases tissue stiffness. Increased stiffness further enhances the proliferation of cardiac fibroblasts, creating a vicious cycle of fibrosis that ultimately leads to heart failure. Understanding the molecular mechanisms that control the proliferation of cardiac fibroblasts is therefore essential in order to identify novel targets for new therapies that can break this cycle of fibrosis.

Our group has characterised the molecular signalling pathways controlling cardiovascular cell proliferation. We have identified the second messenger cyclic-AMP as an important factor that repressed cardiac fibroblast proliferation. Our research has linked the anti-proliferative and anti –fibrotic effects of cAMP to inhibition of the actin cytoskeleton polymerisation. This in turn controls expression of proliferation genes that are dependent of the actin cytoskeleton organisation. Importantly, similar signalling mechanism appear to be activated during fibrosis. This suggests that the pro-fibrotic effect of increased tissue stiffness and the anti-fibrotic effects of cAMP both converge at a common signalling mechanism.

This three year PhD studentship will characterise theses novel molecular mechanisms using a range of molecular and cell biology techniques. The project will focus of the role of transcriptional mechanisms controlling fibrosis and proliferation genes and the role of novel circular RNAs in this. The project offers the opportunity to study in an excellent research environment, in a research institute with world class facilities and resources devoted to understanding the cellular and molecular mechanisms of cardiovascular disease and driving new translational therapies for patients. We have an opportunity available for exceptional candidates with an interest in the areas of vascular biology, cell signalling and gene expression regulation and drug-discovery. Candidates should have at least a 2:1 BSc in a biological science.

Tuition fees: Standard University of Bristol tuition fees plus £10,000/year bench fees.