About the Project
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350 million people in Africa, Asia, the Americas and the Mediterranean are at risk from the Leishmaniases, a group of neglected tropical diseases caused by the single-celled Leishmania parasite and spread by sand flies, with up to 1 million new cases and 65,000 deaths annually.
Symptoms include disfiguring skin lesions, destruction of mucous membranes, visceral disease and death.
Leishmaniasis disproportionately affects the poor and malnourished, with disease incidence influenced by environmental and climate changes.
No vaccines exist and available drug treatments are costly, toxic, difficult to administer and may be ineffective due to parasite resistance or host immunosuppression e.g. in HIV patients.
Novel treatments, underpinned by increased biological understanding of their targets, are urgently required.
Essential protein kinases are attractive starting points for drug discovery efforts, since they are clinically druggable.
Further, since cell division is an essential process and divergent in Leishmania compared to mammalian cells, this project will focus on identifying and characterising essential Leishmania cell cycle protein kinases.
Leishmania cell division is complex, involving replication of various single copy organelles as well as dramatic morphological changes, but has been relatively little studied at the molecular level due to challenges in purifying individual cell cycle stages for analysis, and (until recently) a lack of molecular techniques to allow inducible knockout or overexpression of essential regulators.
Our initial experiments indicate that microfluidic focussing of L. mexicana promastigotes through spiral channels has promise as a label-free method to separate individual cell cycle stages based on differences in their shape, size and deformability.
During this PhD project, existing microfluidic sorting protocols will be refined to obtain highly enriched populations of different Leishmania cell cycle stages.
These will then be analysed using comparative proteomics to shed light on the key regulators of cell cycle progression, with a focus on protein kinases.
Molecular and biochemical approaches, including inducible diCre and/or CRISPR/Cas9 technologies and in vitro kinase assays, will be used to functionally characterise protein kinases identified and assess their validity as novel drug targets.
This interdisciplinary project will provide the student with robust training in parasite culturing and genetic manipulation, a range of molecular, biochemical and imaging techniques, and microfluidics and associated MATLAB software.
Further, the student will develop a wide range of transferrable skills, including oral and written presentation skills, critical analysis of literature and data, data reporting and management, statistics and science communication
Funding Notes
This is a 3 year PhD project funded by The Cunningham Trust, an interdisciplinary project supervised by Dr Tansy Hammarton from the Institute of Infection, Immunity & Inflammation and Dr Melanie Jimenez from the School of Engineering at the University of Glasgow.
Applications will be reviewed by the supervisors and by The Cunningham Trust’s Scientific Adviser.
Applicants should have a strong background in at least one of the following: molecular biology, cell biology, biochemistry and parasitology. Prior engineering/microfluidics experience, while advantageous, is not essential.
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