Nucleotide analogues (antimetabolites) are used as anti-cancer treatments in the clinic for many decades, most commonly for the treatment of haematological, breast, ovarian and intestinal cancers. Side effects, acquired resistance, and excessive toxicity however call for refined treatment procedures.
New approaches combining antimetabolites with inhibitors of nucleotide synthesis could potentiate the rate of antimetabolite DNA incorporation. These aberrant nucleotides will serve as a substrate for DNA repair pathways and may lead to excessive DNA damage and cell death specifically in cancer cells. Profiling and categorising cancers according to their expression of DNA repair enzymes and nucleotide metabolism factors could be exploited to specifically enhance treatment efficacy and clinical benefit.
A combination of in silico data interrogation to assess genomic alterations and gene expression with experimental cell biology will be applied. Key techniques will be cell culture, dose response synergy experiments, DNA repair assays such as comet assay, high resolution as well as high content microscopy. Promising combination strategies will be transferred to appropriate 3D spheroid and preclinical cancer models.
Candidates must have a first or upper second class honors degree and significant research experience.
How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply
Please clearly state the prospective main supervisor in the respective box and select 'Oncology & Metabolism' as the department.
Interested candidates should in the first instance contact:
Dr Patrick Herr ([Email Address Removed])