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Bbsrc Mres/Phd Studentship At Newcastle University
How does the Regulation of Ubiquitin/ubiquitin-like Pathways Determine Cellular Responses to Reactive Oxygen Species?
Reference Code: CB108

Name of the supervisors
Professor B Morgan, Institute for Cell and Molecular Biosciences (ICAMB)
Dr J Quinn, Institute for Cell and Molecular Biosciences (ICAMB)

This studentship is sponsored by the Biotechnology and Biological Sciences Research Council (BBSRC) as part of the Doctoral Training Partnership (DTP).

Duration of the award
Four years (MRes Biosciences followed by a three-year PhD).

Project description
Oxidative stress-induced cell damage caused by reactive oxygen species (ROS) is associated with cancer, diabetes, cardiovascular disease, certain neurodegenerative diseases and shortened lifespan. However, ROS are also used by the immune system to defend against disease-causing organisms and play important roles as signalling molecules. Thus, to understand how cells function in ageing and disease it is important to explore the mechanisms by which cells sense and respond to ROS. Recently we and others, using yeast as a model, discovered that conserved antioxidants, previously thought to mainly act in restoring redox homeostasis, play key roles in sensing and signalling the presence of ROS [1,2]. Furthermore, ubiquitin (Ub)/ubiquitin-like (Ubl) modifications of proteins regulate many fundamental biological processes and, excitingly, we recently demonstrated that the specific sensitivity of a conserved ubiquitin pathway enzyme, Cdc34, to oxidation coordinates cell cycle delay to prevent oxidative stress-induced damage [3].

Thus, the project aim is to build on these exciting data, using yeast as a model eukaryote, to determine the regulation and roles of conserved Ub/Ubl protein modifications in responses to ROS. Broadly applicable experience will be obtained of genetics, biochemical, cell biology, microscopy, molecular biology techniques, and also techniques to investigate protein modification.

[1] Day AM et al. (2012) Inactivation of a peroxiredoxin by hydrogen peroxide is critical for thioredoxin-mediated repair of oxidized proteins and cell survival. Mol. Cell 45, 398-408.

[2] Veal EA et al. (2007) Hydrogen peroxide sensing and signaling. Mol. Cell 26, 1-14.

[3] Doris KS et al. (2012) Oxidative stress responses involves oxidation of a conserved ubiquitin pathway enzyme. Mol. Cell. Biol. 32, 4472-4481.

Value of the award and eligibility

Depending on how you meet the BBSRC’s eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees at the UK/EU rate and an annual stipend of £13,726 (2013/14). A partial award covers fees at the UK/EU rate only.

Person specification
Candidates should have or expect to achieve a first-class or upper-second-class Honours degree in a relevant science subject.

How to apply
You must apply through the University’s online postgraduate application form selecting 'Master of Research/Doctor of Philosophy (Medical Sciences) – Cell and Molecular Biosciences’ as the programme of study. Please insert the studentship/partnership reference number CB108. Only mandatory fields need to be completed (no personal statement required) but you must attach a copy of your CV and a covering letter, quoting the title of the studentship and reference number CB108.

Closing date for applications
The post will remain open until a suitable applicant is appointed. Early application is advised.
Sasa Milosevic
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