About the Project
Development of new drugs against parasitic diseases is a major need. We are studying a novel class of boron-containing drugs that have action against trypanosomatids, and for which we have evidence of multiple modes of action and activation. The project will involve the use of genetic screens and followup of identified genes that are required for sensitivity towards a panel of drugs, with a view to understanding the mechanisms responsible for specificity, activation and resistant. Work will initially focus on the African trypanosome, but will extend to additional parasites including Leishmania as the work progresses. Excellent support is offered in collaboration with our mode of action team and colleagues within the DDU.
See fieldlab.org for the lab website and the following articles for recent work in this area.
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
References
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
Programme Title: 4 Year WT PhD Programme 2019
Name of Principle Investigator: Prof Mark C Field
Title of Project: Mode of action of novel trypanosides.
Abstract/Project Description:
Development of new drugs against parasitic diseases is a major need. We are studying a novel class of boron-containing drugs that have action against trypanosomatids, and for which we have evidence of multiple modes of action and activation. The project will involve the use of genetic screens and followup of identified genes that are required for sensitivity towards a panel of drugs, with a view to understanding the mechanisms responsible for specificity, activation and resistant. Work will initially focus on the African trypanosome, but will extend to additional parasites including Leishmania as the work progresses. Excellent support is offered in collaboration with our mode of action team and colleagues within the DDU.
See fieldlab.org for the lab website and the following articles for recent work in this area.
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
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) (in the press)
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