About the Project
Objectives of the PhD
The aim of the project is to recombinantly expressed TbTOPs and to purify the enzymes in active form suitable for inhibitor screening assays. The individual measurable objectives are:
(i) to clone and express TbTOPs as His-tagged proteins,
(ii) to purify His-tagged TbTOPs and to determine their enzymatic activities, and
(iii) to screen compound libraries for specific inhibitors of TbTOPs.
The gene sequences of all TbTOPs are available, and these will be utilized to construct primers for the cloning of these genes in His expression vectors. His-tagged TbTOPs will be purified from cell extracts using Ni2+-NTA agarose columns. The activity of the purified TbTOPs will be determined by using topoisomerase assay kits. Recombinant TbTOPs will then be used for screening small compound libraries using a recently developed high-throughput assay. Promising compounds will be tested for their trypanocidal activity in cell culture with bloodstream forms of T. brucei.
For more information on the supervisor for this project, please go here: https://www.uea.ac.uk/medicine/people/profile/d-steverding
This is a PhD programme.
The start date of the project is 1 October 2020.
The mode of study is full-time. The studentship length is 4 years (3 years period of study, 1 year period of registration).
Please note: Applications are processed as soon as they are received and the project may be filled before the closing date, so early application is encouraged.
Acceptable first degree in Biology, Biochemistry, Microbiology, Parasitology, Molecular Biology, Cell Biology, Biological Science, Biomedical Science, Medical Science, Infectious Disease, Medicinal and Biological Chemistry, Chemistry.
The standard minimum entry requirement is 2:1.
ii) Steverding, D. & Wang, X. (2009) Evaluation of anti-sleeping sickness drugs and topoisomerase inhibitors in combination on Trypanosoma brucei. J. Antimicrob. Chemother. 63, 1293-1295.
iii) Jobe, M., Anwuzia-Iwegbu, C., Banful, A., Bosier, E., Iqbal, M., Jones, K., Lecutier, S.J., Lepper, K., Redmond, M., Ross-Parker, A., Ward, E., Wernham, P., Whidden, E.M., Tyler, K.M. & Steverding, D. (2012) Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi. Mem. Inst. Oswaldo Cruz 107, 946-950.
iv) Ellis, S., Sexton, D.W. & Steverding, D. (2015) Trypanotoxic activity of thiosemicarbazone iron chelators. Exp. Parasitol. 150, 7-12.
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