Dr E A Veal
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
BACKGROUND: Reactive oxygen species (ROS) are natural products of aerobic metabolism but also encountered following exposure to irradiation, drugs/xenobiotics. Oxidative damage caused by ROS is a significant cause of cell death and loss of tissue function during many diseases, and in ageing. Hence, a better understanding of ROS-defence mechanisms and how they are regulated is vital to prevent oxidative damage associated with ageing, as well as to improve the targeting of cancer cells or fungal pathogens with cytotoxic drugs. In this project you will elucidate new mechanisms by which cells sense and respond to ROS. PROJECT: Yeast and human cells are able to buffer their intracellular environment against low levels of hydrogen peroxide, using specific sensor proteins to activate protective responses that limit damage and maintain optimal conditions. Using a novel proteomic approach we have identified many candidate sensors for mediating these protective responses. These include a conserved kinase that protects cancer cells against treatment with irradiation. In this project you will use an integrated approach, involving 2 model systems [1] a yeast that is a well-established model for studies of hydrogen peroxide responses, cell division and ageing and [2] cultured human cell models that are ideal for studies of circadian regulation, cell division and senescence. You will use a wide range of molecular and cellular techniques in these model systems (including genome editing, fluorescent microscopy, methods to examine whether specific proteins are oxidised and real-time bioluminescence imaging of circadian oscillations) to determine how and at what point in a diurnal cycle this kinase is regulated in response to increases in hydrogen peroxide. The data from these studies will be used to inform a mathematical model representing how redox-regulation of this kinase and other signalling proteins, protects cells/organisms against oxidative stress. We expect this knowledge to allow the future design of new, improved strategies to target senescent or cancer cells in animals, or fungal pathogens within their host.
For further information see the website: http://www.ncl.ac.uk/camb/
To apply:
Please submit a full CV and covering letter directly to [Email Address Removed]
Funding Notes
This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,296 for 2016-17). The PhD will start in October 2017. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.
References
Tomalin LE, Day AM, Underwood ZE, Smith GR, Dalle Pezze P, Rallis C, Patel W, Dickinson BC, Bähler J, Brewer TF, Chang CJ-L, Shanley DP, Veal EA (2016) Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed Free Radicals Biol. Med. 95: 333-48. (IF=5.7)
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