| Title | Flagellum length regulation in Leishmania |
|---|---|
| Supervisors | Martin Wiese Craig Roberts |
| Research Area | Protein kinase, Leishmania, signal transduction, protein-protein interaction. Cellular Basis of Disease/Cancer and Inflammatory Disease |
| Description | Protein kinases are important regulators of all cells and play a role in vital processes like differentiation, proliferation, adaptation and motility. Leishmania have to regulate the length of their single flagellum, a highly conserved structure in eukaryotes. Mammalian-stage amastigotes display a flagellum not emerging from the cell surface whereas insect-stage promastigotes show a flagellum at least as long as the spindle-shaped cell body. We have shown that protein kinases are involved in flagellar length regulation and maintenance. As such Leishmania could function as a model organism for flagellar disorders in humans. In this project we will analyse protein kinases involved in flagellar length control. |
| Techniques Used | The project is comprised of a variety of different methods including CRISPR-Cas9, molecular biology, protein biochemistry, cell biology and microscopy. Genes will be cloned using modern cloning technologies. Recombinant proteins will be expressed using bacterial expression systems followed by purification and enzyme assays. Recombinant parasites will be generated and their phenotype analysed. Interactions of protein kinases with their interaction partners will be analysed in vivo using genetically modified parasites and methods, like proximity labelling (BioID), split-reporter proteins and mass spectrometry. |
| References | Wiese, M., Kuhn, D. and C.G. Grünfelder. Protein kinase involved in flagellar-length control. Eukaryot. Cell. Aug 2(4), 769-77 (2003) Bengs, F., Scholz, A., Kuhn, D. and M. Wiese. LmxMPK9, a mitogen-activated protein kinase homologue affects flagellar length in Leishmania mexicana. Mol. Microbiol. 55(5), 1606-1616 (2005) Erdmann, M., Scholz, M., Melzer, I.M., Schmetz, C., and M. Wiese. Interacting protein kinases involved in the regulation of flagellar length. Mol Biol Cell. 17, 2035-2045 (2006) |
| Conditions | Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a Biological Science in addition to receipt of satisfactory references and an IELTS score of 6.5 where appropriate. |
| Bench Fee | Running costs of £12000 p.a. will be associated with this project in addition to University tuition fees. |
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