Biomedical Science PhD Studentships – University Of Liverpool – UK

Posted by kanishk on July 28, 2009

Pigment Deposition In Mouse Models Of Alkaptonuria

Pigmentation In Mouse Models Of Alkaptonuria

Supervisors: Dr JC Jarvis and Professor James Gallagher and Dr D Williams
Department of Human Anatomy and Cell Biology and MRC Centre for Drug Safety Science

Description:
This project will run within a team of enthusiastic and supportive researchers. Please contact Jonathan Jarvis (0151 794 5445) with informal enquiries.
Alkaptonuria is a very rare but debilitating inborn error of metabolism. It becomes a severe arthritic condition that usually requires multiple joint replacements.
• The joint damage is caused by deposition of pigment in the cartilage, related to a high circulating level of Homogentisic acid, consequent on the mutation that destroys the function of Homogentisate 1,2-dioxygenase. Genetically equivalent mouse models now exist, although the AKU mutation does not cause an arthritic condition in the mouse. If this mutation is combined with the equivalent mutation for tyrosinaemia type I (that is non functional Fumarylacetoacetate hydrolase ) then pigmentation has been reported to occur. The tyrosinaemia can be made conditional in the mouse: the drug nitisinone blocks an earlier step in the breakdown of tyrosine. The withdrawal of nitisinone in mice is anecdotally associated with pigmentation.

Objectives:
The aims of the project are to:

Establish the mouse models in Liverpool with HGD and FAH mutations
Look at early deposition of pigment in aorta and joints (histology/em)
Test link between stress and pigment deposition by comparing pigment in exercised and control limbs
Do chemical studies on pigment and begin development of an aptamer specific for ochronotic pigment (in collaboration with the Open University)
Image pigment and decide whether possible to follow deposition and regression processes

Funding:
This project is funded for four years by MRC as a 1+3 in vivo priority studentship with additional support from the British Pharmacological Society.
The project will benefit from association with the Centre for Integrative Mammalian Biology awarded to Liverpool and Manchester.
If appropriate the appointed candidate will follow the MRes in Biomedical Sciences for the first year of appointment.

Please Look At:
www.liverpool.ac.uk/biomedsci/imb/index.htm
findAKUre.org
www.cimb.ls.manchester.ac.uk/?cmp=5