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Self-funded BMS project: Regulation of Leishmania cellular remodelling during life cycle transition


   York Biomedical Research Institute

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  Prof J Mottram, Prof A J Wilkinson  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

This project aims to investigate the signalling pathways that regulate key events in the life cycle of Leishmania and which protein kinases are essential and therefore potentially responsive to chemotherapeutic modulation. Using CRISPR-Cas9 directed loss-of-function genetic screens in Leishmania mexicana we have identified protein kinase genes involved in signalling pathways regulating parasite differentiation during transition between animal and sandfly hosts [1]. Protein kinase genes were also identified that are essential for proliferation and survival of Leishmania once an infection is established in the mammalian host and are therefore potential drug targets [1]. The research will provide insights into protein kinase function in Leishmania and a holistic overview of cell signalling pathways that will integrate into ongoing “omics” analyses within the Leishmania community. The research will focus on elucidating specific signalling pathways involved in regulating the ubiquitin-proteasome system during the cellular remodelling processes that occur during differentiation [2,3]. Techniques to be used will include CRISPR-Cas9 genome editing of Leishmania.

The York Biomedical Research Institute at the University of York is committed to recruiting extraordinary 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 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 Biomedical Science

Start Date: 1st October 2022 


Funding Notes

This is a self-funded PhD research project. Applicants need to have adequate funds to meet the costs of fees and living expenses for the duration of the PhD programme.

References

[1] Baker N, Catta-Preta et al., (2021) Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival. Nat Commun. 12:1244. doi: 10.1038/s41467-021-21360-8.
[2] Damianou, A, et al., (2020) Essential roles for deubiquitination in Leishmania life cycle progression PloS Pathog. 16: e1008455.
[3] Burge, RJ, et al., (2020) Leishmania differentiation requires ubiquitin conjugation mediated by a UBC2-UEV1 E2 complex. PLOS Pathogens 16: e1008784.
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