PhD STUDENTSHIP
Title: Anti-stress gene response in cell and tissue ageing: role of transcription factor nrf2 and effect of dietary activators
Applications are invited for a 3-year PhD studentship funded by a Biotechnology and Biological Sciences Research Council Industrial CASE award in Warwick Medical School, University of Warwick, Coventry, U.K. and Unilever R&D Colworth, Bedfordshire.
The title of the project is “Anti-stress gene response in cell and tissue ageing: role of transcription factor nrf2 and effect of dietary activators” supervised by Professor Paul J Thornalley (Warwick Medical School) and Dr Linda Wainwright (Unilever R&D Colworth, Bedfordshire). The project builds on our recent research on nrf2 regulated protective gene expression and cell senescence. In this project, we will employ human cells in culture expressing a fluorescent nrf2 reporter to identify in real-time dietary bioactives to provide potent and sustained activation of nrf2 and related antioxidant element linked gene expression, metabolism and function in vitro. Synergistic effects of combination of naturally occurring metabolites from a range of fruit and vegetables will be assessed. Mathematical models will be developed and refined to predict time- and dose-dependent vascular protective effects.
You will perform cell culture studies involving transfection and studies of nrf2-linked gene expression. You will be mainly based in Warwick Medical School (Clinical Sciences Research Institute), University of Warwick, Coventry, with a short period of secondment to Unilever R&D Colworth.
Candidates should hold, or expect to receive, a first or upper second class honours degree in biochemistry, cell biology, cellular and molecular biology, pharmacology, biomedical science, medical sciences or related subject. The successful candidate will enrol on a full-time programme of research studies leading to the award of the degree of Doctor of Philosophy. The studentship will comprise fees (at the Home and EU rate only) and an annual BBSRC CASE studentship stipend with CASE enhancement. The studentship will be awarded for a period of up to three years subject to satisfactory progress. The studentship is tenable in the Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K. Informal enquiries should be directed to Paul Thornalley (e-mail: , tel +44 (0) 24 7696 8594).
The closing date for receipt of completed applications is 30th November 2009. Interviews will be held during December 2009. The project is a multi-disciplinary collaborative project between Warwick Medical School, Warwick Systems Biology Centre and Unilever Research.
To apply, please complete the online application form at www.warwick.ac.uk/go/wmsresearchdegrees. Please put the name of the studentship and the post number on the application form. Please also send a current CV and covering letter to Professor Paul J Thornalley, Clinical Sciences Research Institute, Warwick Medical School, University Hospital, Coventry CV2 2DX, U.K. Two signed original academic references to be should also be sent to Samantha Plumb, Research Degrees Course Co-ordinator, Warwick Medical School, The University of Warwick, Gibbet Hill Road, Coventry CV4 7AL UK Tel: 024 7657 5208 Fax: 024 7652 8375
JOB DESCRIPTION
POST TITLE: / BBSRC CASE/Unilever funded PhD StudentshipDEPARTMENT: / Warwick Medical School
SUB-DEPARTMENT: / Clinical Sciences Research Institute
POST RESPONSIBLE TO: / Professor Paul J Thornalley
POST RESPONSIBLE FOR: / Pursuing research project for examination for award of the degree of Doctor of Philosophy
SALARY: / £16,623 pa (including the supplement from Unilever)
REFERENCE NUMBER:
CLOSING DATE: / 30th November 2009
Aim of the project:
To pursue research on the designated project “Anti-stress gene response in cell and tissue ageing: role of transcription factor nrf2 and effect of dietary activators” for 3 years with enrolment on a full-time programme of research studies leading to the award of the degree of Doctor of Philosophy.
Requirements of project:
1. To pursue research on the designated project “Anti-stress gene response in cell and tissue ageing: role of transcription factor nrf2 and effect of dietary activators” for 3 years under the guidance and supervision of Professor Paul J. Thornalley and others (Clinical Sciences Research Institute, Warwick Medical School) and Dr Linda Wainwright (Unilever)
2. To attend training courses as deemed necessary by the supervisors and required for the conducting the programme of research on the designated project.
3. To comply with regulations of Warwick Medical School for enrolment on a full-time programme of research studies leading to the award of the degree of Doctor of Philosophy.
4. To conduct research following procedures of good laboratory practice and standards operating procedures as designated by the local guidelines of the Clinical Sciences Research Institute, Warwick Medical School
5. To work alongside areas where research is conducted on clinical human samples. You must have appropriate immunisation prior to taking up the appointment.
PERSON SPECIFICATION
POST TITLE: BBSRC CASE/Unilever funded PhD Studentship
DEPARTMENT: Warwick Medical School, Clinical Sciences Research Institute
The Person Specification focuses on the knowledge, skills, experience and qualifications required to undertake the role effectively.
REQUIREMENTSThe postholder must be able
to demonstrate: / ESSENTIAL (E) or
DESIRABLE (D)
REQUIREMENTS / MEASURED BY:
a) Application Form
b) Test/Exercise
c) Interview
d) Presentation
A first or upper second class honours degree or equivalent in biochemistry, cell biology, cellular and molecular biology, pharmacology, biomedical science, medical sciences or related subject (or expect to shortly receive one). / E / a
Good communication and written skills / E / a, c
Ability to:
· Reason accurately
· Think logically
· Solve problems
· Work independently
· Innovate
· Assimilate information
· Make decisions
· Act on own initiative / E / a, c
The ability to interact with research team members in a co-operative, responsible and reliable manner / E / c
The ability to work to tight schedules and to make effective use of time and facilities / E / c
Computer literate / E / a, c
Familiar with Microsoft Office / D / a, c
Understanding of biochemistry, metabolism and molecular physiology / D / a, c
Interest in dietary relationships to health and ageing – particularly protective gene expression likely contributing to healthy ageing / D / c
In accordance with the national agenda in higher education to modernise pay and grading structures, the University of Warwick has completed a significant programme of change that has seen the introduction of a new pay spine and single job evaluation scheme. The work commenced in September 2004 and was communicated and implemented across the University in August 2006.
All salaries detailed within this recruitment document are post implementation and will be subject to normal salary progression as defined by the relevant terms and conditions of service.
In conjunction with this, the University is now commencing discussions with trade unions to harmonise terms and conditions. Further details on this phase of the project will be available shortly.
FURTHER PARTICULARS
Research team of Professor Thornalley
Professor Paul J. Thornalley is Professor of Metabolic Biochemistry and Systems Biology. He leads a Protein Damage and Systems Biology research group co-supervised by Dr Naila Rabbani - Assistant Professor of Experimental Systems Biology. Both have joint appointments in Warwick Medical School and Systems Biology Centre (SBC). They are both based in modern, well-equipped laboratories in the CSRI, University Hospital campus. They have been studying mechanisms underlying ageing-related disorders – particularly proteome damage and metabolic mechanisms protecting against it - for over 25 years. They co-supervise a research team of 12 investigators (6 post-doctoral researchers, 4 PhD students and 2 technicians) based mainly in the CSRI. Cell culture and clinical studies are performed in the CSRI laboratories and pre-clinical in vivo studies in facilities maintained jointly with the Department of Biological Sciences.
Research interests:
Professor Paul J. Thornalley (Recipient of Fritz Worwag International Science Prize 2007 for studies on vitamins in medicine):
ANTIOXIDANT RESPONSE ELEMENT-LINKED GENE EXPRESSION: Isothiocyanate-mediated activation, nrf2 transcription factor signal transduction, and prevention of cancer, vascular disease and ageing.
PROTEIN GLYCATION, OXIDATION AND NITRATION: Physiological formation and quantitation of glycation, oxidation and nitration adducts; proteolytic processing of damaged proteins; involvement in the chronic complications of diabetes, cardiovascular disease, atherosclerosis, renal failure, cirrhosis, Alzheimer’s disease, arthritis and ageing.
PROTEOMICS: Identification of proteins and sites of damage, functional effects, modelling and bioinformatics.
VASCULAR DISEASE: Biochemical dysfunction, metabolic monitoring and therapy.
THIAMINE METABOLISM AND THERAPY IN DIABETES: Clinical trial of thiamine and thiamine derivatives for the prevention of vascular complications of diabetes, studies of cellular and physiological basis of disturbance in thiamine metabolism in diabetes and link to risk of vascular complications
Dr Naila Rabbani (Recipient of Shaul Massry Prize on Uremic Research and Toxicity, 2005):
ANTIOXIDANT RESPONSE ELEMENT-LINKED GENE EXPRESSION: Small molecular activation of transcription factor nrf2 and anti-lipogenic effect.
VASCULAR DISEASE: Disturbance of lipoprotein metabolism – particularly relate to post-translational modifications of low density lipoprotein (LDL) and high density lipoprotein (HDL).
PROTEIN GLYCATION, OXIDATION AND NITRATION: Physiological formation and quantitation of glycation, oxidation and nitration adducts – particularly lipoproteins and involvement in the chronic complications of diabetes
THIAMINE METABOLISM AND THERAPY IN DIABETES: Clinical trial of thiamine and thiamine derivatives for the prevention of vascular complications of diabetes, studies of cellular and physiological basis of disturbance in thiamine metabolism in diabetes and link to risk of vascular complications
OTHERS INVOLVED IN THE PROJECT
Experimental data on similar projects on-going in the Protein Damage and Systems Biology research group are being used to develop and refine a mathematical model of dietary bioactive activated and nrf2-regulated protective gene expression. The mathematical modelling is led by Professor David Rand.
Professor David Rand (Warwick Systems Biology Centre) led earlier research in nonlinear dynamics and was awarded the LMS Whitehead prize. Over the past decade he has worked on applying mathematics to biological problems: spatial systems in ecology, epidemiology and evolutionary theory, pair approximations, and mathematical descriptions of biological processes at the molecular and cellular level – including circadian rhythms, new statistical techniques for the analysis of the sort of biological systems data being considered in this grant. Since 1998 he has been an investigator on over £7m of grants from EPSRC, BBSRC, the EU and the Wellcome Trust. He is director of the Warwick SBC. He also directs the Interdisciplinary Programme in Cellular Regulation (IPCR) spanning biological, mathematical and physical sciences and is one of the three main investigators.
Activation of transcription factor nrf2 will be followed in this project by time-lapsed video microscopy of green fluorescent fusion constructs of nrf2 and related proteins. This will be supervised by Dr Tony Shymgol.
Dr Tony Shmygol (Warwick Medical School) Tony Shmygol’s laboratory is also based in the CSRI where he uses multidimensional digital imaging and confocal microscopy combined with mathematical modelling to investigate the signalling pathways. His experience in time-lapsed video microscopy and related instrumentation will we employed on this project. He will be designated as second supervsiro of this project.
Relevant publications:
1. Xue, M.Z. and Thornalley, P.J. (2007) Sulforaphane suppresses reactive oxygen species and induces transcriptional activation of antioxidant response element related genes expression in human BJ-5ta fibroblasts. Comp. Biochem. Physiol. 146A, S55 – S56
2. Foyer, C.H., Faragher, R., Thornalley, P.J. (2009) Redox metabolism and longevity relationships in animals and plants. Preface. SEB Exp Biol Ser 62, xix-xxx, 2009Bottom of Form
3. Xue, M. Qian, Q., Antonysunil, A., Rabbani, N., Babaei-Jadidi, R. and Thornalley, P.J. (2008) Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes 57, 2809 -2817.
4. Xue, M.Z., AntonySunil, A., Rabbani, N. and Thornalley, P.J. (2009) Chapter 15. Protein damage by glycation, oxidation and nitration in the ageing process. Advances in quantitation of protein damage and the emerging importance of decline in enzymatic defences as the ageing phenotype develops. In: Redox Metabolism and Longevity Relationships in Animals and Plants (Foyer, C., Faraghar, R. and Thornalley, P.J. eds), SEB Exp Biol Ser 62, pp. 227 – 265.
5. Thornalley, P.J, Xue, M. and Rabbani, N. (2009) Methodologies for in-vitro and in-vivo activity of bioactive compounds. In: Health-Promoting Properties of Fruits and Vegetables (Terry, L. ed.), CABI, Oxford, UK., in press.
The University
The University of Warwick is arguably the most successful of UK universities founded within the past half-century, and has earned an outstanding reputation both for research and teaching. Warwick is comfortably ranked within the top ten of all UK university newspaper rankings including 6th in the most recent Sunday Times Good University Guide.
Founded in 1965 Warwick has been a unique and uniquely successful British university combining a “can-do” entrepreneurial spirit with a commitment to absolute academic excellence. Professor Nigel Thrift, Warwick’s 5th Vice-Chancellor, was appointed last year to transform the University from a leading university within the UK to become one of the world’s top 50 universities by 2015. A new university strategy will be launched in autumn 2007 as a result of extensive consultation with staff, students and Warwick’s many external stakeholders.
Warwick employs nearly 5,000 members of staff, of whom 1,500 are academic and research staff spread across 28 academic departments and 30 research centres; 91% of the academic staff are in departments with research ratings of 5 or 5*. Of the 24 departments assessed under the subject review process, 22 were rated excellent (or scored 21 or more out of 24) for teaching quality.
The University of Warwick has a total student population of over 20,000 of whom approximately 12,000 are undergraduates and almost 7,000 are postgraduates. Nearly one-quarter of Warwick’s students are international, helping to create a vibrant and cosmopolitan campus environment which is valued and celebrated by the University.
The University’s campus, located on a 400-acre site spanning the south west boundary of Coventry and the county of Warwick, has an open and pleasant outlook and was voted “Best University Campus” in a national student poll published by the Times Higher Education Supplement in 2006. The campus offers excellent sporting facilities, including a swimming pool, a newly refurbished gym, a climbing wall, an all weather running track and acres of football and rugby pitches.