Self-funded PhD opportunities

Anti-Cancer Properties of Metformin and other Biguanides

  • Application end date: Applications accepted all year round
  • Funding Availability: Self-funded PhD students only
  • Department: School of Pharmacy and Biomedical Sciences
  • PhD Supervisor: Dr James R. Smith, Dr Samantha C. Higgins and Dr Peter B.

Metformin is the first line of defence drug used to control Type 2 diabetes (T2D). It operates by decreasing glucose absorption in the gastrointestinal tract, increasing insulin sensitivity and glucose uptake into cells, and reducing gluconeogenesis in the liver. It is particularly attractive since it does not cause hypoglycemia. Metformin belongs to a class of compounds known as the biguanides, which also include phenformin and buformin, although these two drugs were withdrawn due to their lactic acidosis side-effects. More recently, it has been found that biguanides, including those mentioned above, have anti-cancer properties. This appears to be due to their ability to disrupt the Warburg effect. Intermediates in the mechanism have been identified in the literatures and we hypothesise that a particular ringed compound might be key to inhibiting an enzyme system to cause targeted cytotoxicity to cancer cells.

The project will involve the synthesis and purification of metformin in quantities required for cytotoxicity testing. A range of other biguanides will also be synthesised (including microwave methods), which will be reacted to form ringed target compounds. These will be added to various glioma cells to investigate in vitro cytotoxicity. Drug delivery via nanocarriers through our blood brain barrier in vitro model may also be investigated. Techniques will include organic synthesis, spectroscopy (NMR, FTIR), tissue culture, flow cytometry, confocal microscopy, live cell imaging, cytotoxicity testing (MTT/MTS) and other techniques as required. The student will be working as a member of the Cellular and Molecular Neurooncology Group, within the Institute of Biomedical and Biomolecular Sciences (IBBS).

In addition you will have access to a skills development program run by the university’s Graduate School. The experimental and analytical skills developed during this project will prepare the student well for a future career in academia or industry.

Research Group Web Site http://www.port.ac.uk/school-of-pharmacy-and-biomedical-sciences/research/

Funding Status: Self funded - University fees (currently, £13,100 for International Students and £4,052 for Home and EU students) + (plus additional bench fees of £6,000 per annum).

Search terms: cancer, neurooncology, neuroscience, brain, cell biology, metformin, drugs.