£6,000 PhD Scholarship | APPLY NOW £6,000 PhD Scholarship | APPLY NOW

Development of DNA repair therapeutics to overcome cancer resistance to chemotherapy


   Faculty of Life Sciences

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Prof Sherif El-Khamisy, Dr Mateusz Jurga, Prof Klaus Pors  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Reduced oxygen supply (hypoxia) is a common feature of cells distant to blood vessels in most solid cancers. It reduces the effectiveness of chemotherapy and promotes cancer aggressiveness and spread. Therefore, developing new strategies to kill the hypoxic regions of tumours is of great importance. We recently discovered that a DNA repair protein called senataxin is produced in greater quantities in hypoxic cells and uncovered a mechanism for its regulation. Senataxin is a protein that deconstructs a nucleic acid structure consisting of two DNA strands plus one RNA strand, called an R-loop. When R-loops accumulate they cause genomic damage, which is a common mechanism by which anti-cancer drugs kill cancer cells. The increased level of senataxin in hypoxia protects tumour cells from anti-cancer drugs in the same way it protects against R-loop damage. In this project, we will understand how senataxin is controlled and develop new methods to reduce its levels in the hypoxic cancer cells, which is expected to increase the effectiveness of anti-cancer treatments.

The Institute of Cancer Therapeutics (ICT) is the home of multidisciplinary teams working together to make fundamental discoveries and take them to the clinic. Early diagnosis and personalised healthcare are the future to winning the battle against human disease including cancer. At the ICT, we fuse genetics, cell biology, medicinal chemistry and pharmacology to take medicines and diagnostics from concept to clinic.

The ICT is world-renowned for research, training and partnership with industry. We are located in a purpose-built building carrying over 30 years’ experience in drug discovery, pharmacology, metabolite profiling and pharmacokinetics. We work closely with a large network including the Universities of Stanford, Harvard, Oxford, Cambridge, Sheffield, the Bradford Royal Infirmary, St James Hospital and the Royal Hallamshire.

The student is expected to have a first or upper second-class hons in pharmaceutical, biological, medical or biochemical science (or equivalent). A master’s degree in a related field or a track record of laboratory training is preferred but enthusiasm and commitment to teamwork is more important.

In line with Brad-ATTAIN, we particularly encourage applications from the following underrepresented groups as identified by the OfS

  1. Black, Asian and Ethnic Minority students
  2. Disabled students 
  3. Female students
  4. Care leavers
  5. Polar Q1 and Q2 students
  6. Refugees given the sanctuary status of the university
  7. Estranged students
  8. Gypsy, Roma, Traveller students
  9. Children from military families, veterans and partners of military personnel.

Funding Notes

A home PhD scholarship has been made available through the generous support provided by the Aillie and Ade fund, which covers tuition and bench fees, and provides a stiped at UKRI rates (currently £16,042 per year).

References

Jurga M, Abugable AA, Goldman ASH, El-Khamisy SF. USP11 controls R-loops by regulating senataxin proteostasis. Nature Commun. 2021 Sep 15;12(1):5156. doi: 10.1038/s41467-021-25459-w. PMID: 34526504; PMCID: PMC8443744.
Ramachandran S, Ma TS, Griffin J, Ng N, Foskolou IP, Hwang MS, Victori P, Cheng WC, Buffa FM, Leszczynska KB, El-Khamisy SF, Gromak N, Hammond EM. Hypoxia-induced SETX links replication stress with the unfolded protein response. Nature Commun. 2021 Jun 17;12(1):3686. doi: 10.1038/s41467-021-24066-z. PMID: 34140498; PMCID: PMC8211819.
Search Suggestions
Search suggestions

Based on your current searches we recommend the following search filters.

PhD saved successfully
View saved PhDs