Development of DNA repair therapeutics to overcome cancer resistance to chemotherapy

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.