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Investigating the role of exosomes and the cell fate regulator, ASCL1 in driving, and maintaining lethal Neuroendocrine transdifferentiation of prostate cancer


College of Medicine and Veterinary Medicine

About the Project

Background:

Prostate cancer is the leading cause of male cancer-related deaths in the UK and treatment resistance is a major clinical problem. Neuroendocrine prostate cancer (NEPC) emerges as cells transdifferentiate into neuroendocrine (NE)-like cells to evade therapy. Fundamental gaps in our understanding of NEPC mean clinicians lack biomarkers to track its emergence and drugs to treat it.
There is a strong correlation between expression of cell fate regulator, ASCL1 and acquisition of NE cells in prostate cancer. ASCL1 co-ordinates progenitor differentiation into neuronal cells, therefore ASCL1 expression may be pivotal in driving NE transdifferentiation.
Exosomes are implicated in many aspects of tumourigenesis due to their ability to modulate neighbouring cell function. Exosomes’ role in paracrine communication means they may be central to NE cell orchestration of NEPC evolution and potential as much needed circulating biomarkers to track NEPC disease progression.

About the project:
The aim is to investigate molecular mechanisms driving NE switching of prostate cancer cells and exosome communication’s role in NEPC. In particular: 1) ASCL1/hASH1’s role in driving and maintaining NE transdifferentiation, 2) the reversibility of NE transdifferentiation and 3) characterisation of exosomes released from NEPC cells.

Molecular techniques including, gene knockdown, immunoblotting, qRT-PCR and confocal microscopy will be used.

Academic qualifications:

A first degree (2:1 or higher) in biomedical sciences, or equivalent discipline if outside the UK, with a good fundamental knowledge of cancer cell biology, cell communication and molecular biology associated techniques; a Masters in a relevant field is desirable.

It is expected to have successful candidate start February/March 2021.

How to apply:

Applications including a full CV with names and addresses (including email addresses) of two academic referees and a statement of interest, should be sent to:

When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.



Funding Notes

The Melville Trust funded studentship is available for three years’ full-time study, and the award provides tuition fees (Home/EU rate), stipend and a small consumables budget. An overseas fee-paying student would need to pay the difference in the tuition fee.

Eligibility:

All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. prior to commencement.
If English is not an applicant’s first language, an IELTS/TOEFL certificate should be submitted with the application as evidence that the candidate meets the language requirements for PhD study at Edinburgh University.

References

Fraser JA, Sutton JE, Tazayoni S, Bruce I, Poole AV (2019) hASH1 nuclear localisation persists in neuroendocrine prostate cancer cells, even upon reintroduction of androgen. Scientific Reports 9:19076. doi:10.1038/s41598-019-55665-y

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