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Targeting metabolic vulnerabilities in human prostate cancer

  • Full or part time
  • Application Deadline
    Wednesday, April 22, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Number of awards
1

Start date and duration
28 September 2020

Overview
Prostate cancer is strongly associated with ageing and a major clinical problem for older men. It is the UKs commonest male cancer and one in four have fatal disease. New therapeutic approaches are urgently required and vulnerabilities in cancer metabolism related to mitochondrial respiratory chain oxidative phosphorylation (OXPHOS) offer such opportunity. Accumulation of age-related mutations in mitochondrial DNA (mtDNA), which encode for OXPHOS protein complexes, is a major phenomenon in the prostate and our recent work revealed that specific deficiencies are tolerated in cancer (complexes I and IV). This studentship aims to generate an innovative prostate cancer model harbouring specific mitochondriopathies for preclinical drug testing. The student will use established techniques to deplete mitochondria from iPSCs and replace with organelles from an archive of characterised mutated mitochondria. These modified iPSCs will generate prostate organoids and the student will test established drugs targeting specific OXPHOS complexes. Additionally, this work will define treatment sensitivities in the context of specific nuclear driver mutations, appreciating co-operation between both the nuclear and mitochondrial genomes, to reveal translationally relevant vulnerabilities for precision-medicine clinical trials.

Sponsor
Margaret Barbour Foundation

Name of supervisor(s)
Dr Rakesh Heer (https://bit.ly/2Q8watX), Clinical Senior Lecturer/Consultant, Translational & Clinical Research Institute (https://bit.ly/2IEsBYr)
Dr Laura Greaves (https://bit.ly/3cOhAln), Newcastle University Research Fellow, Biosciences Institute(https://bit.ly/2xy0qbp)
Prof Craig Robson (https://bit.ly/2THrRYX), Professor of Molecular Urology, Translational & Clinical Research Institute

Eligibility Criteria
Essential:

Previous MRes study
Experience in iPSC culture
CRISPR experience
Experience in lentiviral gene-modification
Hands on experience in FACS
A 2:1 honours degree, or international equivalent.
IELTS 6.5 overall (with a minimum of 5.5 in all other sub-skills)

Desirable:

Experience in mitochondrial-related molecular biology

How to apply
You must apply through the University’s online postgraduate application form (https://bit.ly/2U5uCT0). Only mandatory fields need to be completed. However, you will need to include the following information:

insert the programme code 8300F in the programme of study section
select ‘PhD in the Faculty of Medical Sciences – Cancer Research as the programme of study
insert the studentship code TC005 in the studentship/partnership reference field
attacha covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code TC005 and state how your interests and experience relate to the project
attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications

Contact
Dr Rakesh Heer

Funding Notes

100% of UK/EU tuition fees paid and annual living expenses of £15,009 (full award). Successful international candidates will be required to make up the difference between the UK/EU fees and international fees.

Related Subjects

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