Screening for New Natural Drugs and Drug-Resistance Determinants in Trypanosomatids
Lead Supervisor: Dr David Horn (LSHTM)
Co-Supervisor: Dr Deniz Tasdemir (SoP)
Trypanosomatids are protozoan parasites spread by insect vectors, causing more than one million deaths each year. There are currently few drugs to treat these neglected diseases and the emergence of resistance is a major problem. We aim to identify novel anti-trypanosomal drugs of natural origin and, using a generic system for the elucidation of drug-resistance mechanisms, to develop therapies with reduced likelihood of resistance. The proposed project brings together expertise in complex natural extract-screening and fractionation by the Tasdemir group with RNA interference (RNAi) forward genetic screening for drug-resistance mechanisms developed by the Horn group. Our novel drug identification and validation approach will allow the discovery of novel trypanocidal compounds and parallel assessment of resistance potential.
It is essential that candidates have
- a degree in a relevant subject (2:1 or above);
- the ability to work independently and/or as part of a team;
- good communication skills, both written and verbal.
It is desirable that candidates have
- laboratory skills in molecular biology/cell culture/chemistry;
- a range of computer skills.
The cross-disciplinary nature of this project will provide the student with a range of techniques at the cutting edge of genetics, biology and natural product chemistry. At LSHTM, techniques will include parasite culture, RNA interference, DNA manipulation and bioinformatics. At the SoP, the main focus will be purification and structural analysis of bioactive compounds using chromatographic and spectroscopic methods. It is expected that the student will benefit from engaging in the work of groups in two laboratories at different institutions, where similar objectives are approached in different ways. This particular synergy will enhance opportunities for employment in either academia or industry.
Key References
1. Glover, L., McCulloch, R., and Horn, D. (2008) Nucleic Acids Res. 36: 2608-2618
2. Tasdemir, D., Kaiser, M., Brun, R., Yardley, V., Schmidt, T., Tosun, F., and Ruedi, P. (2006) Antimicrob. Agents Chemother. 50: 1352-1364.
3. Karioti, A., Skaltsa, H., Linden, A., Perozzo, R., and Tasdemir, D. (2007) J.Org. Chem., 72: 8103-8106.
4. Wilkinson. S.r., Taylor, M.c., Horn, D., Kelly, J.M., and Cheeseman, I. (2008) Proc. Natl. Acad. Sci. U S A 105: 5022-5027.
Further details about the project may be obtained from:
Supervisor: Dr David Horn; david.horn@lshtm.ac.uk
http://homepages.lshtm.ac.uk/~ipmbdhor/dhhome.htm
Tel: +44 (0) 20 7753 5845
Co-Supervisor: Dr Deniz Tasdemir; deniz.tasdemir@pharmacy.ac.uk
http://www.pharmacy.ac.uk/deniz_tasdemir.html
Tel: +44 (0) 20 7753-5845
Further information about PhDs at The London School of Hygiene & Tropical Medicine is available from:
http://www.lshtm.ac.uk/prospectus/research/ditd.html
Application forms and details about how to apply are available from:
http://www.lshtm.ac.uk/prospectus/howto/research_app_form_2009-10.pdf
Registry: http://intra.lshtm.ac.uk/registry/
Tel: +44 (0) 20 7299 4646
E-mail: registry@lshtm.ac.uk
Additional Application Requirements
Please provide a full CV and complete any Additional Sections on The Standard Application Form
Closing date for applications is 25 February 2009
