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PhD Studentship: Metabolism in Heart Failure - Using Human Pluripotent Stem Cells to Model Disease

University of East Anglia

Qualification Type: PhD
Location: Norwich
Funding for: UK Students, EU Students, International Students
Funding amount: Competition Funded Project (Home and International)
Hours: Full Time
Placed On: 31st October 2023
Closes: 15th January 2024
Reference: SMITHJ_U24FMH

Background 

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During differentiation of pluripotent stem cells into cardiomyocytes their metabolism matures, however, cardiac diseases such as heart failure secondary to myocardial infarction are characterised by perturbed metabolism with a shift towards immature metabolism. This proposed PhD project will use state-of-the art techniques to generate human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) and fibroblasts (hiPSC-FBs) to investigate the role of metabolism in various cardiac disease models.

Aims 

To model and investigate changes that occur in cardiovascular disease states using hiPSC-CMs and hiPSC-FBs with particular focus on metabolism of cardiac cells to gain knowledge of disease mechanisms, and to evaluate novel pharmaceutical treatment strategies.        

Research methodology

Gene edited hiPSC lines will be differentiated into contractile beating cardiomyocytes and secretory active cardiac fibroblasts. Either in isolation or in co-culture, these cells will be exposed to various stressors to model cardiovascular disease. The models will be validated and interrogated to understand the changes that occur under these stressors. A range of state-of-the art laboratory techniques and methods will be used to investigate the cells, including cell viability and proliferation assays, immunohistochemistry, as well as functional assessment of contractility and metabolism (Seahorse and Metabolic assays). Gene expression and protein expression analysis using reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively, will be utilised to investigate the pathways involved. Mass spectrometric analysis will be used to disentangle the underlying mechanisms further.

Training

As well as the specific technical training detailed above, students will have access to high-quality training in scientific and generic skills, as well as access to a wide range of seminars and training opportunities setting them up for a future in science.

Person specification

Essential: First degree (e.g. BSc, BA, MBBS) in relevant subject area (Biological Sciences, Medicine).

Desirable: Experience in cell culture and basic laboratory research. 

This PhD project is in a Faculty of Medicine and Health Sciences competition for funded studentships.  These studentships are funded for 3 years and comprise UK (Home) fees, an annual stipend of £18,622 and £1,000 per annum for research training (RTSG). International applicants may apply but are required to secure additional funding to fund the difference between UK and overseas tuition fees (visit: https://www.uea.ac.uk/study/fees-and-funding/fees for details of Home and Overseas fee rates).

Primary Supervisor: James Smith

Start Date: October 2024

For more information on this project, please visit https://www.uea.ac.uk/search/courses/

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