Self-funded PhD opportunities

Characterisation on a novel protease control switch: implications for inflammatory arthritis

  • Application end date: All year round
  • Funding Availability: Self-funded PhD students only
  • Department: School of Biological Sciences
  • PhD Supervisor: Dr Andy Pickford, Dr John McGeehan, Dr Louise Butt

Project code: 

A common pathological feature of the chronic inflammatory condition rheumatoid arthritis (RA) is the gradual destruction of the articular cartilage that lines the synovial joints of the body.  One of the predominant macromolecular components of cartilage is fibrillar collagen.  The enzymes primarily responsible for breaking down this collagen in RA are members of the matrix metalloproteinase (MMP) family.  These collagen-degrading MMP enzymes are secreted by cells as inactive zymogens (proMMPs) which are then activated in the extracellular space.  Therefore, the mechanism of activation of these collagenases is of great biomedical significance.

Typically, proMMPs consist of an auto-inhibitory pro-peptide (PRO) domain, a catalytic (CAT) domain and a hemopexin-like domain.  The thiol group of a cysteine residue within the PRO domain binds the catalytic zinc ion in the CAT domain active site cleft, keeping the enzyme inactive.  Activation of proMMPs involves disruption of this cysteine-zinc interaction.

The objective of this project is to investigate the mechanism by which the collagenase MMPs are activated by a variety of other proteases, with a particular focus on protein-protein complexes that regulate the activation process.  The PhD student will receive training in a wide range of biochemical and biophysical techniques, including site-directed mutagenesis, recombinant protein production, surface plasmon resonance (SPR), nuclear magnetic resonance (NMR) spectroscopy, small-angle x-ray scattering (SAXS) and x-ray crystallography.

Funding Notes:

This PhD opportunity is available to self-funded students. Bench fees will apply. For more information please contact the project supervisor, Dr Andy Pickford (andy.pickford@port.ac.uk).

How to apply:

To apply or make an enquiry, please visit postgraduate research: Biological sciences

All applications should use our standard application forms and follow the instructions given under the ‘Research Degrees’ heading on the following webpages: http://www.port.ac.uk/application-fees-and-funding/applying-postgraduate/#rd.

When applying please note the project code -