Trypanosome morphogenesis and pathogenicity
Supervisor: Dr Paul McKean
The African trypanosome Trypanosoma brucei is a pathogen of considerable medical importance in sub-Saharan Africa: over 60 million people are at risk of developing African sleeping sickness, there is little prospect for the development of a vaccine, and existing chemotherapeutic treatments are unsatisfactory (due to inherent toxicity, poor efficacy and increasing evidence of drug resistance). Thus, there is an urgent need to develop novel chemotherapeutic strategies.Building from our existing studies on the role of the flagellum in cell morphogenesis and division (e.g. Broadhead et al 2006; Davidge et al 2006), we have begun to consider other aspects of cytoskeletal re-modelling during the trypanosome division cycle. Using a combination of bioinformatic, biochemical and proteomic approaches we have identified a catalogue of novel, trypanosomatid-specific proteins, which are associated with the sub-pellicular microtubule-based cytoskeleton that defines trypanosome cell shape. Some of these microtubule-associated proteins (MAPs) are essential and our data suggest regulated assembly of these MAPs as distinct complexes and/or in a defined temporal order on microtubules during trypanosome cell division.The aim of this project is to undertake a detailed interrogation of newly identified MAPs to provide greater understanding of their functional role in directing morphogenesis and to characterise functional interactions between individual MAPs. The study of cell shape and morphogenesis is of fundamental cell biology interest, but in addition could potentially identify novel drug targets for the sleeping sickness parasite.The successful applicant will receive excellent training in a wide range of molecular, biochemical and cell biology techniques in newly refurbished microbiology laboratories within the Faculty of Health and Medicine at Lancaster University. The project will be co-supervised by Dr Paul McKean and Dr Michael Ginger - informal enquiries are welcome to either supervisor.