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Investigating novel epigenetic modifiers of PARP inhibition


Project Description

Research interests/description of main research theme:

Applications are invited for a 4-year fully-funded PhD Studentship starting in October 2020 in the laboratory of Dr Martin Higgs at the University of Birmingham (http://www.birmingham.ac.uk/research/cancer-genomics/research/lysine-methylation-dna-damage/index.aspx).
PARP inhibitors offer an exciting clinical option to treat certain kinds of hereditary breast and ovarian cancer, and their use is also being investigated for the treatment of other types of tumours, including prostate cancer and leukemia. However, resistance to these drugs is a major problem. We have discovered a new way that cancer cells can become resistant to PARP inhibitors by deregulation of epigenetic modifications. This studentship will examine the mechanisms behind this resistance, and how we can target these resistant cells using other therapies. The findings from this project will be vital in our understanding of drug resistance in cancer, and may lead to the development of better treatment strategies.

Person Specification

Applicants should have a strong background in biological sciences, and ideally a background in cellular and molecular biology. They should be able to demonstrate prior competence in a laboratory environment. They should have a commitment to research in genome stability, cancer biology or epigenetics, and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in Biomedical sciences, Biochemistry or Cellular Biology.

How to apply
Informal enquiries should be directed to Dr Martin Higgs ().
Applications should be directed to David Piela (email ). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.

Shortlisted applicants will be required to attend an interview in mid/late March 2020. This will include meeting the research group and a tour of the labs.

Funding Notes

This PhD is funded by Cancer Research UK and includes bench fees, tuition fees and a living stipend ~£19,000 pa.

N.B. Fees are only funded to Home/EU rate so international; applications must be able self-fund the difference.

References

Gogola E, Rottenberg S, Jonkers J. Resistance to PARP Inhibitors: Lessons from Preclinical Models of BRCA-Associated Cancer. Annual Review of Cancer Biology. 2019; 3:235-254
Higgs MR, Sato K, Reynolds JJ, Begum S, Bayley R, Goula A, Vernet A, Paquin KL, Skalnik DG, Kobayashi W, Takata M, Howlett NG, Kurumizaka H, Kimura H, Stewart GS. Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2. Mol Cell. 2018; 71(1):25-41.
Begum S, Goula A, Bayley R, Higgs MR. On your marks, get SET(D1A): the race to protect stalled replication forks. Mol Cell Oncol. 2018; 5(6):e1511209.
Weston VJ, Oldreive CE, Skowronska A, Oscier DG, Pratt G, Dyer MJ, Smith G, Powell JE, Rudzki Z, Kearns P, Moss PA, Taylor AM, Stankovic T. The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Blood. 2010; 116(22):4578-87.

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