Uncovering the fundamental mechanisms of cardiac differentiation from human stem cells

   Faculty of Biology, Medicine and Health

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  Dr Matthew Birket  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Heart diseases, adult and congenital, are a major burden to health in the UK and we urgently need new ways to treat them. Stem cells offer hope by providing a means to make contracting heart muscle cells “in a dish”, and therefore a way to study these diseases in the lab. These cells could also be used in patients, to mend injured hearts after a heart attack.

A problem we currently face which limits our ability to make the most of stem cells, is that our understanding of cardiac cell development in humans remains incomplete, specifically how the progenitor cells, which give rise to the heart, are programmed to acquire cardiac potential. Human pluripotent stem cells (hPSCs) provide an opportunity to make equivalent progenitors in vitro, but their current medical use is restricted by the uncertain molecular basis of their biological function. Heterogeneity in cellular competence limits confidence in their application and solving this will enable radical advances in applications such as congenital disease modelling and regenerative medicine. This research will address the underlying problem by investigating the gene regulatory mechanisms of the ancient cardiac transcription factor NKX2-5, to better understand the molecular circuitry of cardiac potential and fate determination.

The project will utilise an NKX2-5-GFP hPSC fluorescent reporter line recently published by the lab, combined with a cutting-edge CRISPR library-based deletion screen (international collaboration) to test the function of putative regulatory elements of NKX2-5, including gene enhancers. We will integrate our latest data from single cell RNA-sequencing during cardiac differentiation and perform new experiments to test the signalling pathways and transcription factors regulating this key developmental step in which NKX2-5 expression is switched on. This new knowledge will improve our ability to identify and benchmark cardiac progenitors and help unlock the vast potential of stem cells for cardiology research and therapy.

This BHF funded PhD project will enable the candidate to gain internationally-recognised expertise in hPSC biology, gene editing and cardiac development – skills now highly valued in academic, clinical and industrial research. The successful applicant will be embedded in a dynamic and exciting lab environment and supported by two experienced supervisors (M Birket and N Bobola). A comprehensive training program will also be provided by The University of Manchester’s Doctoral Academy. 

How To Apply

1.     For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/).  Interested candidates must first make contact with the Primary Supervisor prior to submitting a formal application, to discuss their interest and suitability for the project. On the online application form select PhD Stem Cell Research.

Funding will cover UK tuition fees and stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a scholarship that will enable a full studentship to be awarded to international applicants. This full studentship will only be awarded to exceptional quality candidates, due to the competitive nature of this funding. Please contact the supervisor before making an application.

Entry Criteria

Applicants are expected to hold (or about to obtain) a minimum upper second class undergraduate honours degree (or equivalent) in a related subject e.g. genetics or molecular biology. Candidates with experience in pluripotent stem cell biology, gene regulation or gene editing, with an interest in developmental biology, are encouraged to apply.

 Equality, Diversity & Inclusion

is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Biological Sciences (4) Medicine (26)

Funding Notes

This project is funded by the British Heart Foundation (BHF). Studentship funding is for a duration of three years to commence on April 2024 and covers UK tuition fees and a UKRI stipend.