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Deubiquitinases and differentiation in unicellular eukaryotes


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 fully-funded studentship part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. 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, chemical, and/or physical science. Students with mathematical backgrounds who are interested in using their skills in addressing biological questions are also welcome to apply.

References

Eligibility: The studentships are available to UK and EU students who meet the UK residency requirements. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award. Further information about eligibility for Research Council UK funding

Shortlisting: Applicants will be notified if they have been selected for interview in the week commencing on Monday 28 January 2019.

Interviews: Shortlisted applicants will be invited for an interview to take place in the Department of Biology at the University of York on Wednesday 6 and Thursday 7 February 2019. Prior to the interview candidates will be asked to give a 5 minute presentation on a research project carried out by them.

Related Subjects

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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