Regulation of Human Cardiac Fibroblast Function by Specific microRNAs

Heart tissue comprises several different cell types with the majority being either muscle cells (cardiomyocytes) or cells that produce the structural scaffold of the heart (cardiac fibroblasts). Although once viewed as relatively passive players that solely regulate extracellular matrix remodelling, cardiac fibroblasts are now acknowledged as being primary nodal regulators of multiple aspects of cardiac function under both physiological and pathophysiological conditions. For example, cardiac fibroblasts are essential drivers of the fibrosis and hypertrophy that characterise adverse cardiac remodelling associated with heart failure progression. Like all cells, cardiac fibroblasts express a class of recently discovered regulatory molecules called “microRNAs” (miRNAs). Recent studies by our group have identified several miRNAs expressed by cardiac fibroblasts whose levels are altered under conditions of cardiac dysfunction and remodelling. This study will use human cardiac fibroblasts cultured from different patients to investigate the role and regulation of these miRNAs. Specifically, the project will: (1) explore the effects of these miRNAs on multiple aspects of cardiac fibroblast function relevant to the cardiac remodelling process (cell proliferation, migration, differentiation, gene and protein expression); (2) evaluate the influence of type 2 diabetes on miRNA expression and cardiac fibroblast function; (3) determine the stimuli, signalling pathways and regulatory mechanisms that control expression of these miRNAs; and (4) identify the target genes responsible for modulation of fibroblast function. By studying these specific miRNAs and their regulatory mechanisms in human cardiac fibroblasts, we hope to reveal potential therapeutic targets for reducing adverse myocardial remodelling and heart failure progression in man.

This project will combine the supervisors’ long-standing expertise in cardiac fibroblast signalling (Dr Turner) and miRNAs (Dr Forbes) to explore the role of specific miRNAs in regulating cardiac fibroblast function. All the techniques required to complete this work are in use within our research groups, and the student will receive hands-on training by the supervisors and their lab members. These techniques include human cardiac fibroblast culture, cell function assays, analysis of gene and protein expression, miRNA measurement and modulation, ChIP assays, pyrosequencing, SILAC proteomics and general molecular biology techniques. Hence, the project will provide the student with training in a wide array of cellular and molecular biology techniques that will provide the platform for progression as a cardiovascular research scientist.

Eligibility:
You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject area, e.g. biological sciences, biomedical sciences or biochemistry. Applicants should not already have been awarded a doctoral degree.

The Faculty minimum requirements for candidates whose first language is not English are:
• British Council IELTS – score of 6.5 overall, with no element less than 6.0
• TOEFL iBT – overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to apply:

To apply for this project applicants should complete a Faculty Scholarship Application form using the link below https://medicinehealth.leeds.ac.uk/downloads/download/78/fmh_scholarship_application_form_2018_2019 and send this alongside a full academic CV, degree certificates and transcripts to the Faculty Graduate School at [Email Address Removed]

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to [Email Address Removed] by no later than Friday 20 September 2019.

Any queries regarding the application process should be directed to [Email Address Removed].