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Understanding cardiomyocyte proliferation and improving organoid models of heart diseases

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  • Full or part time
    Dr A Kanhere
    Prof K Stellos
    Dr P Sharma
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Heart failure is a serious and often fatal medical condition caused by inability of heart to pump enough blood around the body. It is one of the leading causes of death in ageing population. One of the core causes behind heart failure is the inability of adult mammalian heart to regenerate heart muscle cells or cardiomyocytes after they are lost due to other health conditions. Remarkably, human cardiomyocytes can divide in foetal state but lose their ability to regenerate soon after birth. In sharp contrast, heart regeneration is common in non-mammalian vertebrates such as zebrafish. Remarkably, adult zebrafish can regenerate its heart after loss of as much as 20% of its ventricle. Understanding how cardiomyocytes divide is a key to the treatment of heart diseases. In addition, finding means of boosting cardiomyocyte proliferation will help in culturing them longer in laboratory, improving models of heart function and understanding pathology of heart diseases.

This project is focused on a protein, JARID2, which is indispensable for normal heart development. JARID2 is also important in regulating cardiomyocyte proliferation. Yet, functional characterisation of Jarid2 in cardiomyocytes has not been carried out. In addition, evolutionary changes in Jarid2 function are not investigated.

We have made an exciting discovery that, in cells, JARID2 exists in two forms. Could these two forms together regulate cardiomyocyte growth and differentiation? Could this also explain increased ability of zebrafish cardiomyocytes to proliferate? Can we use JARID2’s ability to regulate cell proliferation to improve in vitro models of heart diseases? This project will be focused on these questions.

The recruited PhD student will use modern technologies such as transcriptomics and organoid formation. Further, the student will also employ molecular and cell biology approaches to investigate the molecular mechanisms underlying the JARID2 mediated regulation of cardiomyocytes. Finally, the biological relevance of these findings will be validated in organoids/organoid models.

This is a unique opportunity to work in a multi-disciplinary environment in two world-leading universities in the UK. In addition to scientific training, there is ample opportunity to develop communication and presentation skills by participating in many scientific meetings, collaborations and publications. In short, this project will prepare you in skills needed for a competitive career in academia as well as industry.


HOW TO APPLY:
Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

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