Dr Dave Gilham & Dr Dominic Rothwell

In this fully-funded 4-year BBSRC ICASE project, we plan to develop methods and equipment to improve the quality of tissue cryopreservation. The eventual target is to satisfy the demands of high quality tissue for current state-of-the-art molecular and ultrastructural biological analyses. The project will be run in collaboration with Asymptote, a leading specialist in cryopreservation.

The PhD will test the quality of preserved tissue by immunohistochemical and electron microscopy studies while examining the feasibility to isolate nucleic acid from laser captured material to perform next generation sequencing analysis. Importantly, the project will focus upon streamlining the overall process to enable the rapid delivery of molecular analysis that could be used for genetic screening and systems biology investigations.

Chemical fixation (e.g formalin) is a convenient method that is routinely used to preserve tissues for routine pathological analysis but is limited for more intensive study due to antigen disruption and nucleic acid fragmentation. Vitrification followed by freeze substitution represents the current gold standard preparative method for the high-resolution imaging of biological materials.

However, current equipment for vitrification is large, expensive and requires skilled operators. In this project, we will develop Progressive Lowering of Temperature (PLT) techniques to produce samples that maintain good ultrastructure in the frozen state with high cell viability upon thawing.

Importantly, the development of the Stirling Cryocooler platform by Asymptote provides opportunity to develop PLT capability that would obviate the requirement for expensive process equipment currently used to vitrify samples by rapid cooling.

The study will span the Institute of Cancer Sciences (ICS) and Asymptote, Cambridge. Regular placements at Asymptote will be incorporated as part of the equipment design and manufacture, so providing research experience in a commercial environment.

Extensive training will be provided in the development of new bioprocessing equipment, the physics of freezing biological tissues and ultrastructural analysis. Such skills-sets will equip the successful candidate to progress into a postdoctoral career in a variety of clinical and biomedical areas.

The 4-year full-time studentship provides full support for UK/EU tuition fees and an annual minimum tax-free stipend at RCUK rates (currently £13, 863). The project is due to commence October 2015 and is open to UK/EU* nationals only due to the nature of the funding.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in either a physical science (engineering, physics, maths) or life science (biological/medical science). A Masters degree in a similar discipline would be beneficial as would previous experience of some of the techniques referenced above.

Please direct applications in the following format to Dr Dave Gilham (david.gilham<στο>ics.manchester.ac.uk):               

•       Academic CV

•       Official academic transcripts

•       Contact details for two suitable referees

•       A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Gilham.

*Applicants must be UK/EU nationals who have resided in the UK since at least 1 September 2012 in order to qualify for full funding.

http://www.cancer.manchester.ac.uk/staff/78188

http://www.cancer.manchester.ac.uk/

http://asymptote.co.uk/

http://www.mhs.manchester.ac.uk/postgraduate/