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MRes/PhD Studentship - Understanding the role of the Peroxiredoxin Redox Switch in signalling, stress resistance and ageing - Newcastle University - Institute for Cell and Molecular Biosciences

BBSRC MRes/PhD Studentship - Understanding the role of the Peroxiredoxin Redox Switch in signalling, stress resistance and ageing - Newcastle University - Institute for Cell and Molecular Biosciences.

Peroxiredoxins (Prx) are abundant, cellular antioxidants with important roles in protecting against oxidative damage, cancer and ageing (Veal et al 2007 Mol Cell, Olahova et al 2008 PNAS). Intriguingly, the thioredoxin peroxidase activity of eukaryotic Prx is highly sensitive to inactivation by hyperoxidation of a catalytic cysteine (Wood et al 2003 Science). The expression of sulphiredoxin (Srx) enzymes that specifically reverse Prx hyperoxidation, is tightly controlled, suggesting that the redox state of Prx is also tightly regulated (Biteau et al 2003 Nature, Bozonet et al 2005 JBC). However, the function of this Prx redox switch in controlling responses to hydrogen peroxide is unclear. One suggestion is that Prx hyperoxidation may be important to allow hydrogen peroxide-signalling (Wood et al 2003 Science). Other studies suggest hyperoxidation converts Prx from thioredoxin peroxidases to chaperones (Jang et al 2004 Cell).

The aim of this project is to use experimental and computational modelling (Kirkwood et al 2003 Nature Rev Mol Cell Biol) to develop a dynamic model of hydrogen peroxide responses to understand how the Prx redox switch influences cellular and whole organism redox homeostasis and ageing. This will be achieved by:

1. Using the yeast Schizosaccharomyces pombe to develop a dynamic model to understand how the Prx redox switch contributes to cellular redox homeostasis. S.pombe is easily genetically manipulated, amenable to quantitative study, and, importantly, contains single genes for components of the system (eg. Prx) rendering it uniquely well-suited for developing a dynamic model.

2. Applying the cellular level dynamic model developed in [1] to the nematode worm C.elegans, an established model for ageing research, to explore the role of the Prx redox switch in different cell types and in whole organism ageing.

Together these approaches will help us understand the links between oxidative stress and ageing/age-related diseases eg neurological and cardiovascular diseases and cancer.

Project start date: September 2010.

Eligibility and Value of the Award
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 and an annual stipend of £13,290 (2009/10). A partial award covers fees only.

Person Specification
You should have, or expect to achieve, a minimum of an upper-second-class Honours degree, or equivalent, in a relevant subject such as biochemistry, biological sciences, biomedical sciences, cell biology, genetics, microbiology, molecular biology, pharmacology.

How to Apply
You must complete the University's postgraduate application form. Select "Master of Research/Doctor of Philosophy (Medical Sciences) – Cell and Molecular Biosciences" as the programme of study. 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 CMB80.

Closing date: prompt application is advised as this post is only available until a suitable candidate is appointed.