How to heal an injured heart? – a study of gene expression regulation in cardiomyocytes

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. One form of JARID2 promotes cell proliferation and the other form inhibits it. Could these two forms, with their opposing functions, regulate cardiomyocyte growth?  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.

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.

Informal enquiries may be made to a.kanhere@liverpool.ac.uk

HOW TO APPLY

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk with a CV and a covering letter, 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. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the NLD BBSRC DTP Studentship Application Details Form (Word document) to bbsrcdtp@liverpool.ac.uk, noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.