Multidisciplinary discovery of new therapeutic targets in ischemic heart disease through intercellular signalling pathways
Ischemic heart disease (heart attack) is the foremost cause of death globally although current reperfusion therapies have dramatically increased immediate survival after ischemic disease, these therapies cannot restore the lost heart muscle cells (cardiomyocytes). Preventing death of cardiomyocytes would have immediate benefits to reduce infarct size (the damaged area) further improving survival as well as reducing the risk of future heart failure. The only definitive treatment for heart failure is heart transplantation, a solution available just to a restricted number of patients. Indeed, even small increases of infarct size correlate with considerable increased risk of mortality 1-year later including the risk of heart failure.
Previously, it was proposed to replace lost cardiac muscle cells with the transplantation of new cardiac progenitors which can subsequently repopulate the heart muscle. Although long-term engraftment has proven very difficult to achieve in practice, grafting new cells into the heart after ischemic injury surprisingly still benefits long-term cardiac function. An evolving consensus is that transplanted cells contribute to heart cells survival and repair via signals they send out to existing cardiomyocytes. We recently found that signals secreted by progenitor cells prevent cardiomyocyte death following oxidative stress comparable to that seen during reperfusion of heart muscle following a heart attack. The secreted proteins suppressed programme cell death (apoptosis), reduced reactive oxygen content, and preserved mitochondrial function in human induced pluripotent cells (iPSC)-derived cardiomyocytes. This model provides a relevant human platform to investigate how extracellular signals augment cardiac muscle survival and cardioprotection.
You will take a multidisciplinary approach building on the unique skill-sets of the collaborating labs to dissect the mechanisms mediating cardiomyocyte protection in a humanized model. You will learn to use our ischemia-reperfusion model to study the interactions between cardiac progenitor cells and iPSC-derived cardiomyocytes; learn and use proteomics approaches to study the intercellular signalling mediating cardiac muscle protection; and validate potential novel drug targets using gain and loss of function experiments with recombinant proteins, CRISPR/Cas9 gene editing, blocking antibodies and small molecule inhibitors.
To apply, you will need to complete the following two steps:
1) Please email Veena Dhulipala ([Email Address Removed]) with the following documents.
- Your CV
- The names and addresses of at least two academic referees
- A personal statement of no more than 1,000 words explaining your interest in the project
2) Please complete the Imperial College London’s online application site (https://imperialuk.elluciancrmrecruit.com/Apply/Account/Login).
Please note that you will have to complete both steps for your application to be considered. Please assume that your application has not been successful if you have not heard from us within a month of the closing date.
Closing date for all applications: 23.59 on Sunday 19th January 2020
Interviews will be held in early February 2020
Applicants must hold, or expect to obtain, a first or upper second-class honours degree or equivalent in an appropriate subject from a recognised academic institution. Candidates must fulfill College admissions criteria and meet BHF residency requirements.
We are looking for a highly motivated and engaged student for this exciting multidisciplinary project requiring independent work and an excellent capacity to work in team. Previous theoretical and practical experience in an area including aspects of molecular science (molecular biology, biochemistry or chemical biology) is essential.
How good is research at Imperial College London in Clinical Medicine?
FTE Category A staff submitted: 334.18
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