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Molecular adaptation in Leishmania parasites


Project Description

Leishmania are single-celled protozoan parasites of the Order Trypanosomatidae that cause the neglected tropical disease leishmaniasis. Leishmania are highly unusual eukaryotes whose cell biology and evolution are poorly understood. The Leishmania group diverged from the crown group eukaryotes (plants, animals, fungi) billions of years ago, so their molecular biology has many unusual features including polycistronic transcription (1), non-typical post-transcriptional gene regulation (2), and unique cellular structures that have evolved since their divergence from crown group eukaryotes (3).
This project will study the molecular evolution of Leishmania species within the context of the Trypanosomatidae, using both bioinformatic and biochemical approaches. You will produce multiple complete genomes from Trypanosomatidae species that diverged >100 million years ago (4) using 3rd generation sequencing technology. From these genomes you’ll be able to identify genes that have evolved rapidly, gene families that have been lost or gained and gene families that are unique to intracellular parasitism. The first focus will be on the “dark” genome, genes that currently have unknown function. The second will be to understand the genomic changes that have led to the most severe form of the disease, visceral leishmaniasis, which is fatal if untreated. These evolutionary analyses will use a combination of comparative genomes (analysing differences between species) and analysis of within-species diversity.
Importantly, you’ll have the opportunity to determine the cellular and molecular consequences of the most striking adaptive changes. By applying CRISPR/Cas9 gene editing technology, you will recreate or revert gene evolution, then use biochemical/cellular approaches to describe the phenotypic consequences of these genetic alterations, with a focus on intracellular parasitism.
At York you’ll be part of a well-resourced community of world-leading Leishmania researchers with active collaborations in Africa, Brazil, Sri Lanka, ensuring that your work will be well-guided, utilised effectively and widely dispersed to the community.

Funding Notes

The studentship is fully funded for three years by the Department of Biology and covers: (i) a tax-free annual stipend at the standard Research Council rate (£15,000 estimated for 2020 entry), (ii) research costs, and (iii) tuition fees at the UK/EU rate. The successful candidate will be required to contribute to departmental teaching by undertaking 30 hours/year demonstrating for Biology practicals.

References

Entry requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, in a are invited to apply. We welcome applications from students with backgrounds in any relevant biosciences subject that provides the necessary skills, knowledge and experience the research project.

Start date: October 2020

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

Research output data provided by the Research Excellence Framework (REF)

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