- Opens: Thursday 5 March 2020
- Number of places: 1
- Duration: 36 Months
OverviewProtein kinase, Leishmania, signal transduction, protein-protein interaction. Cellular Basis of Disease/Cancer and Inflammatory Disease
B.Sc. in a Biological Science at Upper Second Class or above or equivalent qualification
Protein kinases are important regulators of all cells and play an important role in vital processes like differentiation, proliferation, adaptation and motility. The human parasite Leishmania like other eukaryotes relies on signal transduction via reversible phosphorylation. As such parasite protein kinases are potential drug targets to be used to treat leishmaniasis, a human disease, which dependent on the parasite species and the immunological background of the host can be fatal. In fact, protein kinases are part of signal transduction networks. In this project we want to identify activators of Leishmania protein kinases and their substrates. This will allow to set up enzymatic assays, which can be used to identify specific inhibitors for parasite protein kinases.
The project is comprised of a variety of different methods including CRISPR-Cas9, molecular biology, protein biochemistry, cell biology and screening. Genes will be cloned using modern cloning technologies. Recombinant proteins will be expressed using bacterial expression systems followed by purification and enzyme assays. 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.
Wiese, M.. A mitogen-activated (MAP) protein kinase homologue of Leishmania mexicana is essential for parasite survival in the infected host. EMBO J., 17, 2619-2628 (1998)
Wiese, M. Leishmania MAP kinases – familiar proteins in an unusual context. Internat. J. Parasitol. 37(10), 1053-62 (2007)
John von Freyend S, Rosenqvist H, Fink A, Melzer IM, Clos J, Jensen ON, and Wiese M. LmxMPK4, an essential mitogen-activated protein kinase of Leishmania mexicana is phosphorylated and activated by the STE7-like protein kinase LmxMKK5. Int J Parasitol. 40(8), 969-78 (2010)
Applicant will need to self-fund, find sponsorship for tuition and bench fees of £12000 per annum for duration of studies
Applicants can apply using the University PEGASUS Application System https://www.strath.ac.uk/science/strathclydeinstituteofpharmacybiomedicalsciences/studywithus-postgraduate/phd/