Developing prodrugs to target neglected tropical diseases
Supervisor: Dr Shane Wilkinson
Project description
Over 20 million people suffer from diseases caused by the protozoan parasites responsible for American trypanosomiasis, African trypanosomiasis & leishmaniasis. With no prospect of vaccines, chemotherapy is of major importance. However, current treatments are unsatisfactory & the development of new drugs is a priority. Previous drug screening programmes carried out at SBCS have identified several, potent anti-parasitic nitro- & quinone-based compounds that show little/no cytotoxicity to mammalian cells. These compounds invariably function as prodrugs & following activation are postulated to mediate their mode of action by promoting DNA damage.
The aim of this PhD project is to build on these findings to:
- Establish whether these compounds promote DNA damage in parasite & mammalian cells
- Evaluate the role played by parasite DNA repair pathways to fix this damage.
Additionally, the successful applicant will develop tagged intracellular parasite lines for additional drug screening programmes. It is envisaged that by understanding how these bioreductive compounds mediate their anti-parasitic activities will inform the development of new chemical structures that have translational potential.
Facilities and training
The successful applicant will receive a comprehensive training in molecular biology & biochemical skills. Instructions in good microbiological practice will be given, with emphasis on the culturing & genetic manipulation of category 2 & 3 pathogens, as well as on mammalian tissue culture work.
Personalised training in writing and communication skills will be provided, complemented with generic transferable skills training from the QMUL Learning Institute.
References
View a list of publications from Dr Shane Wilkinson