MRes/PhD Studentship Examining the effects of G protein-coupled receptors and inflammatory signalling pathways on cartilage homeostasis using a systems biology approach



Reference Code: IA066

Closing Date: 16th August 2013

Details:

Name of the supervisor(s)
Dr C Proctor, Institute for Ageing and Health

Professor D Rowan, Institute of Cellular Medicine

Professor F Falciani, University of Liverpool

Sponsor
The MRC – Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between the universities of Liverpool, Newcastle and Sheffield. The aim of the centre is to understand the processes and effects of ageing in tissues of the musculoskeletal system leading to osteoarthritis, osteoporosis and muscle weakness, how ageing contributes to disease and how this can be treated or prevented.

Duration of the award
Four year MRes/Phd or three year PhD

Project description
Ageing is associated with OA, a disease we have previously shown to involve the serine protease matriptase which is an important activator of collagen-degrading enzymes (MMPs) and cartilage breakdown. We have shown that proteinase-activated receptor-2 (PAR-2), a G protein-coupled receptor (GPCR) leads to enhanced MMP activation.

The aims of this project are to:

1) examine which GPCRs are important in MMP up-regulation;
2) deduce the signalling pathway(s) leading from GPCR activation to increased expression and activity of MMP-1 and MMP-13.

The student will carry out experiments to establish which specific GPCRs, in addition to PAR-2, are important in cartilage degradation. The student will also develop a mechanistic computer simulation model based on current knowledge of the signalling pathways involved in GPCR signalling leading to up-regulation and increased activity of MMPs. The model will assist in design of experiments, e.g. inhibiting different parts of the pathways predicted by the model.

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To verify the signalling pathways, the student will make use of data from other on-going projects (e.g. proteomics data) and develop a network model using a systems biology approach. This part of the project will be carried out in Liverpool under the guidance of Professor Falciani.

Value of the award and eligibility
Students should have home or EU student status: studentships for UK applicants comprise tuition fees, research support costs and a tax-free stipend at the Research Council rate, while EU applicants may be eligible for a full award if they have been ordinarily resident in the UK for 3 years preceding the date of application.

Person specification
Candidates should hold a first-class or upper-second-class honours degree in Biological Sciences or an equivalent degree. Some experience in laboratory work and computational skills will be an advantage.

How to apply
Interested candidates should contact Dr Carole Proctor in the first instance at [email protected] or on 0191 248 1209.

To apply for this studentship, please complete the CIMA studentship application form and send, along with 2 x page CV, to: [email protected].

Further information
For further details, please contact:
Dr Carole Proctor
E-mail: [email protected]
Telephone: +44 (0) 191 248 1209.

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