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Deubiquitinases and differentiation in Leishmania


Project Description

The ubiqutin proteasome system is the primary mechanism for protein
degradation in eukaryotic cells. Ubiquitin is conjugated to target proteins
through a sequential mechanism involving E1, E2 and E3 conjugating enzymes.
Ubiquitin homeostasis is regulated by the action of deubiquitinases (DUBs),
which cleave ubiqutin from ubiqutinated proteins, as well as via processing of
ubiquitin precursors. We have shown using genome editing that 5 DUBs are
essential for life cycle transitions of the parasitic protozoon Leishmania, which
differentiates from a free living promastigote in the sandfly to obligate
intracellular amastigote in the mammalian host. In this project we aim to (1)
investigate the essential role of DUBs in the cellular remodelling that occurs
during promastigote to amastigote differentiation (2) Identify the substrate
proteins and interactors for DUB2, a DUB that is essential for ubiquitin
homeostasis (3) Crystallise DUB2 and determine its structure, as a prelude for a
structure based drug discovery programme. The project will utilise a variety of
approaches including Turbo BioID to define the DUB interactome and to identify
potential substrates, CRISPR-Cas9 genome editing to validate interactions and
to investigate the role of DUBs in differentiation and protein expression/
crystallography to investigate mechanisms of DUB activity.

Funding Notes

Funding: This is a 4-year studentship fully-funded by the Department of Biology at the University of York for entry in October 2019. The studentship covers: (i) a tax-free stipend at the standard Research Council rate (around £15,000 per year), (ii) tuition fees at UK/EU rate, (iii) research consumables and training necessary for the project.

Entry requirements: At least an upper second class honours degree, or equivalent in any biological science.

References

Eligibility: The studentship is available to UK and EU students only.

Interviews: Tuesday 23 July 2019 in the Department of Biology at the University of York.

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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