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PhD Studentship - The Role of Mitochondria in the Relationship between Ageing, Oxidative Stress and Nutritional Status - Newcastle University - Institute of Cellular Medicine

PhD Studentship - The Role of Mitochondria in the Relationship between Ageing, Oxidative Stress and Nutritional Status - Newcastle University - Institute of Cellular Medicine.

Mitochondrial dysfunction caused by oxidative damage has been proposed as an underlying cause of the ageing process. Mitochondria possess their own genetic material (mitochondrial DNA or mtDNA) and the accumulation of mutations in this genome is thought to be one of the causes of age-dependent cellular decline. These mutations may be generated principally through mechanisms involving production of reactive oxygen species (ROS) in the process of elevated oxidative stress.

Skin is a tissue frequently exposed to ultraviolet radiation (UVR) and this radiation enhances ROS production and accelerates ageing. Mitochondrial DNA (mtDNA) deletion mutations have previously been shown to accumulate with photoageing, consistent with the idea that mtDNA damage is generated principally through mechanisms involving oxidative stress. Over the last 15 years, the Birch-Machin group have pioneered the development of the novel idea of using mitochondrial DNA (mtDNA), rather than nuclear DNA, as a more sensitive and reliable biomarker of cumulative UVR-exposure in human skin (Birch-Machin 2006, Birket and Birch-Machin 2007, Birket et al., 2009; Birch-Machin and Swalwell 2009). In addition we have shown in human skin that the accumulation of an ageing-dependent mtDNA mutation is accelerated by exposure to sunlight (Birket & Birch-Machin, 2007).

It is clear that dietary antioxidants from plants (eg carotenoids and flavonoids) are able to provide further protection to the skin following exposure to inducers of oxidative stress. In fact a collaborative pilot in vivo study has shown that lycopene (administered as tomato paste) helped protect the skin from UV-induced erythema and reduced the UV-induced mitochondrial DNA damage (featured on BBC2, Discovery Channel).

This project will aim to provide further understanding of the key role which mitochondria play in the relationship between ageing, oxidative stress and nutritional status using skin as a model (but not exclusive) tissue. This is a multi-disciplinary PhD studentship and includes cellular and molecular biological techniques such as cell culture, FACS analysis, Laser Capture microscopy, UVR dosing regimes, real time PCR, gene array profiling and mutational analysis, electrochemistry, percutaneous absorption, HPLC, mitochondrial functional analysis, ORAC, FRAP assays. The supervisory team will be led by Professor Birch-Machin and includes academic colleagues from the School of Agriculture, Food and Rural Development and the Institute for Research on Environment and Sustainability.

Project start date: October 2010

References
Birch-Machin MA. The role of mitochondria in ageing and carcinogenesis. Clin Exp Dermatol. 2006 31(4):548-52.
Birket M, Birch-Machin MA. The T414G mitochondrial DNA point mutation accumulates in a photoaging-dependent manner in human skin. Ageing Cell. 2007. Aug;6(4):557-64.
Birket, MJ; Passos J; von Zglinicki, T, Birch-Machin MA. The relationship between the agegging- and photo-dependent T414G mitochondrial DNA mutation with cellular senescence and reactive oxygen species production in cultured skin fibroblasts. J. Invest. Dermatol. 2009. 129: 1361-1366.
Birch-Machin MA and Swallwell H. How mitochondria record the effects of UV exposure and oxidative stress using human skin as a model tissue. Mutagenesis (2009; December 2nd doi: 10.1093/mutage/gep061 ahead of print).
Henderson JR, Swalwell H, Boulton SJ, Manning P, McNeil CJ, Birch-Machin MA. Direct, Real-Time Monitoring of Superoxide Generation in Isolated Mitochondria. Free Radical Research 2009 Sep;43(9):796-802.

Eligibility and Value of the Award
The award covers tuition fees at the UK/EU rate and provides an annual stipend (living allowance).Students of any nationality may apply for this project. However, international students will need to source additional funding to cover the extra cost of international tuition fees.

Person Specification
You must have, or expect to achieve, a minimum of an upper-second-class Honours degree in a relevant subject, for example biomedical sciences, biochemistry or biology. Candidates with a Master’s degree are particularly encouraged to apply.

How to Apply
Please complete the University’s online postgraduate application form, selecting ‘PhD in the Faculty of Medical Sciences – Cellular Medicine’ and quoting the reference number CL018. Please attach a copy of your CV and a covering letter to your application.

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