Malaria threatens around 400 million people globally and results in over 0.5 million deaths annually, thereby continuing to be a major public health problem. Malaria is caused by the Plasmodium parasite, which completes its complex lifecycle in a mosquito vector and a mammalian host. Signalling networks regulated by post-translational modifications of proteins are critical for successful growth and transmission of Plasmodium. Although the biology of the parasite invading the host and the vector is remarkably different, several signalling master regulators are expressed and appear to function in both stages. We recently established robust tools for conditional genome engineering and regulation of protein levels of phosphorylating enzymes in in vivo laboratory models of malaria allowing us to precisely dissect the role of signalling modulators at both host and mosquito infecting parasite forms1,2.
Ubiquitylation is a key post-translational modification, which not only marks proteins for degradation by the proteasome, but also alters protein location, function and interactions3. Using small molecule inhibitors, we recently discovered that dynamic ubiquitylation is essential for both malaria parasite infection and transmission. This project will investigate the role of selected ubiquitin modulating enzymes during these two key elements of the parasite life-cycle.
We are seeking a passionate student to join our team where the focus of the project will be tailored to the student’s interest. The PhD project will include innovative chemical-genetic, imaging and proteomic strategies to dissect the role of ubiquitin modulators during malaria parasite infection and transmission and, in turn discover identities of their effectors and regulators. Ultimately you will identify and characterise multifunctional enzymes, which could become robust infection and transmission blocking candidates. You will attend and present at weekly lab meetings, annual departmental meetings and additionally participate in national and international conferences. http://philip.bio.ed.ac.uk
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If you would like us to consider you for one of our scholarships you must apply by 5 January 2020 at the latest.
Philip N & Waters AP. (2015). Conditional degradation of Plasmodium Calcineurin reveals functions in parasite colonization of both host and vector. Cell Host and Microbe, 18(1): 122-131
Kent RS, Modrzynska KM, Cameron R, Philip N, Billker O, Waters AP (2018). Inducible developmental reprogramming redefines commitment to sexual development by malaria parasites. Nature Microbiology; Sept 03Komander, D. Rape, M. The Ubiquitin Code. Annual Review of Biochemistry 81, 203-229 (2012).