Vacancies in the Microvascular Research Laboratories

1. PhD studentship in prostate cancer research (sponsored by Prostate research campaign)

The Microvascular Research Laboratories at the University of Bristol are looking to appoint a PhD student supported by The Prostate Cancer Charity to start in October 2010. The project is to investigate how mRNA splicing of vascular growth factors can regulate angiogenesis and disease progression in prostate cancer. The project will involve cell and molecular biological techniques, in vivo models of prostate cancer, and determination of splice factor expression in human prostate cancer samples. The project will be jointly supervised by Professor David Bates at the University of Bristol, Mr David Gillatt (prostate cancer specialist) at North Bristol NHS Trust , and Dr Michael Ladomery (splicing factor specialist) at the University of the West of England. We are looking for an enthusiastic, bright, motivated individual seeking a career in biomedical science, with an emphasis on cancer or vascular biology. Applicants should have, or expect to have an honours degree a relevant subject, particularly cancer biology, cell or molecular biology, physiology, biological or biomedical sciences, anatomy, zoology or related subjects.  Recent and current final year graduates are eligible. A stipend of ¬£14,000 is available, and fees are included in the project. This project is only available to students eligible for home fees. Applications should be sent to Professor Bates. For further details see www.mvrl.org.

Closing date for applications 1 July 2010.

The project
Although there are only 20,000 genes in human DNA, these can generate over one million different proteins. A great deal of this discrepancy is explained by the process of alternative messenger RNA splicing, such that each gene can generate many mRNAs. In 2002 we found that the key protein involved in providing new blood vessels (angiogenesis) for prostate cancers to grow has two different forms generated by different splicing of the mRNA. One form prevents blood vessels from growing (is anti-angiogenic) and is found in normal but not cancerous prostate.  The way that the cell decides which of these forms to make is through control of proteins involved in binding to the mRNA, by changing the phosphate groups on those proteins. We have found the specific protein pathway that controls splicing using kidney epithelial cells as a model. This pathway involves two key proteins, called ASF, which binds the mRNA, and SRPK1 which modifies ASF. Removing either of these proteins from the cell can increase production of the anti-angiogenic form in kidney epithelial cells. As we know that in prostate cancer there is a change in the isoforms from anti-angiogenic to angiogenic, it is likely that both ASF and SRPK1 are involved (and we have some evidence for this). We are therefore proposing that removing ASF and SRPK1 from prostate cancer cells will increase their production of anti-angiogenic isoforms, so making them less aggressive, grow less quickly and spread more slowly. As we now have some chemicals that specifically block these molecules these might be new therapies for prostate cancer, and we will try and see if these chemicals may be effective in animal models of prostate cancer.

2. PhD Studentship (sponsored by the MRC)

The environment:

The successful candidates will join a thriving and dynamic research team consisting of twenty-three members at the University of Bristol MVRL within the Department of Physiology and Pharmacology. The team includes pre and postdoctoral researchers, clinical researchers, PhD students and technicians. We work on many aspects of microcirculation research with particular emphasis on vascular endothelial growth factor biology in health and disease. The project will enable the successful candidate to be able to learn a large variety of molecular, cell, microscopical and in vivo techniques and gain a good broad background in the physiology and pathology of cancer and vascular biology. The facilities in Southwell Street in Bristol are the highly equipped state of the art integrative Microvascular Research Laboratories. They receive ongoing support from major medical charities such as the Wellcome Trust and the British Heart Foundation as well as the AICR, Cancer Research UK and Diabetes UK, and work with major pharmaceutical companies such as Novartis and Astra Zeneca. This position is an excellent opportunity for a budding research scientist to lay the foundations of a successful career in laboratory based medical research working at the cutting edge of modern medical science. This research area will enable the application of basic cell physiological principles to the vascular biology of prostate cancer. The MVRL is an extremely exciting laboratory to join and we are looking for an individual who is bright, motivated, enthusiastic and who wants to be able to help make breakthroughs in our understanding and treatment of disease states. The laboratories have facilities for in vivo and ex vivo cancer biology, biochemistry, immunology, pharmacology and molecular biology, and excellent microscopy facilities for both light and electron microscopy.

Training
(a) Subject Specific and Generic Research Training The student will receive training by the Graduate School of Biomedical Sciences, the Department, and the MVRL. The GSBS provides training modules in scientific method, including intellectual property, research ethics, safety and radiation protection and risk assessment, data handling, statistical analysis, experimental design, etc. Subject specific training is also provided within GSBS on specialist practical approaches (e.g. making and using antibodies, using DNA databases, gene therapy, transgenic techniques). The GSBS also provides a social coherence for the 150 postgraduate students in the School. Subject specific training is provided within individual research groups, and many generic research skills are also learnt at this level. The student will be joining an interdisciplinary group of scientists within state of the art MVRL run by Prof Bates and Prof Harper.
(b). Transferable Skills Training The student will be expected to present their work at scientific meetings at every opportunity. Oral skills are developed by presentations at regular in-house laboratory meetings, ’Äúwork-in-progress’Äù talks to the Department (3 during three years) and by exposure of students to visiting speakers during seminars, including the MVRL seminars, weekly Departmental seminar series, and Oncology seminar series in the Faculty. Students participate in tutorial and class teaching (~20 hours a year). University Staff Development (USD) and the Department run seminars to instruct students in teaching skills. Writing skills are honed by preparation of articles for publication, and of progress reports at the end of years 1 and 2. Forward planning and time management are encouraged by the supervisors, and informally monitored by the Postgraduate Tutor during yearly meetings. In addition, thesis preparation, writing for publication, leadership, teamwork and organisational skills, time management and personal effectiveness are covered in seminars run by USD. They also hold training days to advise students in each of the three years of their degree (Planning, Managing, and Completing your PhD). Acquisition of generic computing skills occurs within the MVRL, but the Computing Services and USD run courses and workshops devoted to specific IT skills (such as excel, word, etc) and use of internet resources.
(c) Monitoring of Progress. The student will have three advisers ’Äì Prof Bates (principal) Mr Gillatt (secondary clinical), and Dr Ladomery (secondary, scientific). Overlapping supervision works well in the MVRL, and ensures that students get a thorough appreciation of the clinical and specific scientific relevance of their work. Dual supervision is also necessary due to the multi-disciplinary nature of the project and commitments of the principal supervisor, to ensure prompt and regular review and to permit timely trouble-shooting. Progress is monitored by regular one to one sessions with the supervisors (every 2-3 weeks for current students in the lab), regular in-house laboratory meeting presentations, and work-in-progress talks to the Department. A formal review by the Head of Department and the Postgraduate Tutor, preceded by preparation of a written report, is conducted at the end of the 1st and 2nd years. Over the last 5 years the Department of Physiology and Pharmacology has higher than 95% of students completing their studies within four years, and the MVRL has graduated 14/14 students with an average time to submission of 37 months. Further details may be found at the MVRL home page

Details of the Department and working environment are available at http://www.bristol.ac.uk/phys-pharm/ and http://www.bris. ac.uk/ respectively.

Applications

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