Posted on 31 March 2021
The parasite causes the neglected tropical disease leishmaniasis, which is prevalent in the tropics and sub-tropics. Using CRISPR-Cas9 gene editing technology Leishmania mutants were created that were defective in their ability to develop in the insect or mammalian hosts – the research identifies new potential drug targets to treat the disease and increases knowledge on the biology of Leishmania. The work was published in Nature Communications and is currently featured in the “Microbiology and infectious diseases” Editors’ Highlights
The research was carried out in the Department of Biology and York Biomedical Research Institute by two postdoctoral researchers, Nicola Baker and Carolina Catta-Preta as part of a larger team funded by a Wellcome Trust Investigator Award to Jeremy Mottram. An important element was the interdisciplinary collaboration with Ben Powell, Jon Pitchford and Laurence Wilson in the departments of Mathematics and Physics at York, who are developing statistical clustering methods, high-resolution image and motion analysis, and predictive modelling to address a range of emergent problems in Leishmaniasis research. Expertise in sand fly biology was provided by the group of Petr Volf, Charles University Prague and Leishmania motility by Pegine Walrad.
The development of new genetic tools to manipulate Leishmania in this work led to the award of a Wellcome Trust Collaborative Award to Jeremy Mottram and colleagues in Glasgow (Eva Gluenz, PI) and Oxford (Richard Wheeler, Jack Sunter). LeishGEM (the Leishmania genetic modification project) is a 5 year, £2.3m project that will use high throughput genetic tools to understand how Leishmania are such successful pathogens. LeishGEM will determine which proteins are needed for Leishmania parasites to progress through their life cycle and survive in their hosts, which stages they are important for and where they are found in the cell. The two genome-wide screens that are the LeishGEM foundations will also be community resources; Deletion bar-seq and Leishtag. These will transform our understanding of Leishmania molecular cell biology.
Baker, N., Catta-Preta, C.M.C., et al. Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival. Nat Commun 12, 1244 (2021).