The single-cell Leishmania parasite transforms into many different forms during its lifecycle to adapt to very different hosts; moving from mammals to sandflies and back to mammals via sandfly bites. Only Leishmania parasites of certain lifecycle stages can infect and survive in humans. Major changes to the Leishmania parasite's appearance, metabolism and virulence occur during these transitions that enable them to survive. Gene expression in Leishmania relies almost exclusively upon regulation of messenger RNAs. In response to changes in the environment, specific parasite proteins bind mRNAs and target them for protein production to guide and promote adaptation. Proteins that control the adaptation of these parasites enable them to survive in and infect humans. Such proteins are essential for the virulence and spread of the Leishmania parasite infection. Species of Leishmania threaten 350 million people worldwide on four continents. The World Health Organisation estimates 12 million people globally are currently infected and over 1 million new cases occur annually. No vaccine currently exists and available leishmaniasis treatments are threatened by growing resistances and often overwhelmed by acute epidemics that are increasing in occurrence and severity. We have isolated specific RNA binding trans-regulatory proteins that are modified and regulated through arginine methylation. We have shown that levels of the methyltransferase enzyme responsible for this modification modulate Leishmania major infectivity and virulence. The project will focus on how arginine methylation modifies the 3D structure, interaction profile and function of target RNA binding proteins implicit in parasite infectivity and virulence. A molecular-level understanding of this epigenetic process will greatly advance our knowledge of post-transcriptional trans-regulation in Leishmania parasites.
The WR DTP and the University of York are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.
Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions.
Programme: PhD in Mechanistic Biology (4 years)
Start Date: 1st October 2022 (the student will be affiliated with the Department of Biology)
Shortlisted candidates will be interviewed in mid February 2022
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