Funding and Finance

MRes/PhD Studentship - Applying ‘the 3 R’s’ to Liver Fibrosis Research

  • Institute of Cellular Medicine
  • Reference Code: ICM93

Details:

Supervisors: Dr Matthew Wright, Dr Fiona Oakley, Professor Derek Mann
Institute: Institute of Cellular Medicine
Sponsor: NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research)
The NC3Rs is funded by: MRC, BBSRC, Home Office, Wellcome Trust, ABPI, GSK, AstraZeneca, Unilever, The Dow Chemical Company, SC Johnson, Syngenta and Shell
Duration of the award: 4 years (MRes Medical and Molecular Biosciences followed by a three-year PhD)

Liver disease is a major cause of mortality and morbidity and it is predicted to rise in the future [1]. Considerable effort will be needed to find effective treatments. Animal models are essential in this respect because the fibrosis (scarring) process is dependent on multiple cell types within the liver and on tissues outwith the liver. A major aim of this project however, will be to refine the use of animal models and hence reduce the number of animals used in studies.

The project will have two major themes:

 i) to examine the potential of the periportal hepatotoxin drug methapyrilene [2], as a replacement for bile duct ligation (currently used in the model of cholestatic liver disease)
 ii) to examine the use of an antibody [3-6] to image fibrosis severity using IVIS in various animal models of liver disease.

The IVIS Imaging System 200 Series is a state-of-the-art 3D optical imaging system which utilizes Xenogen’s novel patented optical imaging technology to facilitate non-invasive longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in living animals. The system not only generates high quality 3D quantitative images of bioluminescence and fluorescence in vivo and in real time but allows the spectral images to be integrated.

The successful applicant will be required to take the MRes module "Applying ‘the 3R’s’ to in vivo experimental techniques", which will specifically reinforce the philosophy behind ‘the 3R’s ‘(reduction, refinement, replacement).  Additionally the student will attend Home Office modules and will be educated in the ethical considerations of animal research. 

The student will employ a range of in vitro techniques to test the quality of antibody preparations and pre-in vivo testing in tissue culture prior to use in animal studies. The project will therefore give the successful applicant an excellent introduction to in vitro and in vivo techniques, drug-induced liver injury and chronic liver disease, fields of major interest to the pharmaceutical industry and clinicians.  The successful applicant will also be working in a research grouping that has a prominent international profile in liver fibrosis research.

Project start date: September 2010

References
1 Wallace K, Burt AD, Wright MC. Liver fibrosis. Biochem J. 2008;411(1):1-18.
2. Ratra GS, Morgan WA, Mullervy J, Powell CJ, Wright MC. Methapyrilene hepatotoxicity is associated with oxidative stress, mitochondrial disfunction and is prevented by the Ca2+ channel blocker verapamil. Toxicology 1998;130(2-3):79-93.
3. Elrick LJ, Leel V, Blaylock MG, Duncan L, Drever MR, Strachan G, Charlton KA, Koruth M, Porter AJ, Wright MC. Generation of a monoclonal human single chain antibody fragment to hepatic stellate cells--a potential mechanism for targeting liver anti-fibrotic therapeutics. J Hepatol. 2005;42(6):888-96.
4. Douglass A, Wallace K, Parr R, Park J, Durward E, Broadbent I, Barelle C, Porter AJ, Wright MC. Antibody-targeted myofibroblast apoptosis reduces fibrosis during sustained liver injury. J Hepatol. 2008 Jul;49(1):88-98.
5. Douglass A, Wallace K, Koruth M, Barelle C, Porter AJ, Wright MC. Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy. Hepatol Int. 2008;2(4):405-15.
6. Campbell SJ, Anthony DC, Oakley F, Carlsen H, Elsharkawy AM, Blomhoff R, Mann DA. Hepatic nuclear factor kappa B regulates neutrophil recruitment to the injured brain. J Neuropathol Exp Neurol. 2008;67(3):223-30.

Eligibility and Value of the Award
The MRC’s student eligibility criteria apply to this funding. Depending on how you meet the criteria, you may receive a full or partial award. A full award covers tuition fees and an annual stipend of £13,650 (20010/11). A partial award covers fees only.

Person Specification
You should have, or expect to achieve, a first-class or upper-second-class Honours degree, in a relevant subject.

How to Apply
The University's postgraduate application form must be completed; selecting ‘Master of Research/Doctor of Philosophy - Medical Sciences (Cellular Medicine)’as the programme of study and inserting the reference number ICM93. Only mandatory fields need to be completed (no personal statement required) - a CV and covering letter must be attached. The covering letter must state the title of the studentship, quote the reference number ICM93 and state how your interests and experience relate to the project.

Closing date for applications: early application is advised as applications will only be considered until a suitable candidate is found.

Further Information
For more details, please contact Dr Matthew Wright, m.c.wright@ncl.ac.uk, 0191 222 7094, Dr Fiona Oakley fiona.oakley@ncl.ac.uk or Professor Derek Mann, Derek.Mann@ncl.ac.uk.