University of Dundee

China Scholarship Council PhD programme - Anti-parasitic drugs: Mechanisms and protein modifications

The School of Life Sciences at the University of Dundee, joint with the China Scholarship Council (CSC), is proud to be able to offer a scholarship programme for postgraduate research students. The scholarship covers all tuition fees and research fees and provides living expenses and one return flight ticket to successful candidates. There are up to 5 scholarships of 4 years duration available.

The need for new therapeutics against infectious diseases remains critical, and the COVID-19 pandemic has made this clearer than ever. The laboratory is working on understanding the mechanisms by which drugs kill cells in an attempt to both understand how resistance can arise as well as to facilitate the design of improved drugs. Our work focuses on Sleeping Sickness, which is cause by a single celled parasite or trypanosome. We use an array of state of the art methods, including genetics, transcriptomics, proteomics, imaging and biochemistry to probe how drugs interact with these organisms. Our recent work has focused on new compounds that are entering the clinic for treatment of a range of diseases and has uncovered a potential signaling mechanism that mediates protein targeting, mRNA maturation and other functions. The project will investigate the mechanisms that underpin these effects, defining signaling pathways and stress responses and is part of an integrated program of drug development and cell biology investigating post-translational modifications of proteins and how this impacts sensitivity towards drugs.

Examples of recent work from the lab in this area can be found in the following references: 

Zhang, N., Zoltner, M., Ka-Fai Leung, K-F., Scullion, P., Hutchinson, S., del Pino, R.C., Vincent, I., Zhang, Y-K., Freund, Y.R., Alley, M.R.K., Jacobs, R.T., Read, K.D., Barrett, M.P., Horn, D., and Field, M.C., (2018) 'Activation and mechanisms of resistance to phenoxyborole class trypanosides.' PLoS Pathogens 14 e1006850

Wall, R., J., Rico, E., Lukac, I., Zuccotto, F., Elg, S., Gilbert, I.H., Freund, Y., Alley, M.R.K., Field, M.C., Wyllie, S., and Horn, D., (2018) 'The clinical and veterinary trypanocidal oxaboroles target CPSF3.' Proceedings of the National Academy of Sciences (USA) 115 9616 - 9621

Steketee, P.C., Vincent, I.M., Achcar, F., Giordani, F., Kim, D-H., Creek, D.J., Freund, Y., Jacobs, R., Rattigan, K., Horn, D., Field, M.C., MacLeod, A., and Barrett, M.P., (2018) 'Benzoxaborole treatment perturbs S-adenosyl-L-methionine metabolism in Trypanosoma brucei.' PLoS Neglected Tropical Diseases 12(5): e0006450

Zoltner, M., Campagnaro, G.D., Taleva, G., Burrell, A., Cerone, M., Leung, K-F., Achcar, F., Horn, D., Vaughan, S., Gadelha, C., Zíková, A., Barrett, M.P., deKoning, H.P., and Field, M.C., (2020) 'Suramin triggers mitochondrial activation in African bloodstage trypanosomes' Journal of Biological Chemistry 295 8331 - 834