My research is focused on the elucidation of the structure and function of connective tissue macromolecules in health and disease. I have a special interest in the study of glycosaminoglycans (GAGs) and the proteoglycans (PGs) to which they are attached.
Glycosaminoglycans are a class of sulphated polysaccharides found in association with a protein core to form a PG. The structural diversity of GAGs is large and as novel systems are being examined and increasingly sensitive methods of detection and analysis are being used this diversity is expanding.
Important functionality is associated with GAGs and PGs and my work seeks to identify and examine these functions and their relationship with structural motifs especially within the GAG chondroitin / dermatan sulphate.
My work involves the development of GAG isolation and analysis methodologies and the application of these methods to several areas of investigation.
The development of rapid and sensitive methods for the characterization of PGs and GAGs, based at present upon HPLC separation and fluorescent detection, is central to an increasing ability to identify novel structures and bio-functional motifs.
In addition, the development of novel methods for the fragmentation and isolation of PGs and GAGs allows an analytical focus to be placed upon specific motifs identified as having important roles. Study of the age and disease related changes in structure
These enabling methodologies are being used to study the normal age related changes in PG and GAG structure within extracellular matrices, especially cartilage. With these baseline data in place a study of disease related changes, with a special focus upon osteoarthritis (OA), is now possible and this will be a major area of research development.
An understanding of the outcomes of the disease process will inform future work which will seek to understand the processes which are occurring during the progression of the disease. The aim will be to defer, preventing or reverse the progression of the disease, and, explore opportunities for early biochemical tests for the presence of the disease state.
I am also applying new and improved techniques for isolation and analysis to examine the GAGs and PGs from novel biological systems and to probe known systems with the expectation of isolating and identifying previously unidentified, rare, and potentially biologically important, structures.
A knowledge of the spectrum of structures found in vivo will inform future work which seeks to elucidate the enzymes and mechanisms involved in their biosynthesis
I seek to elucidate the interactions and functions of PGs and GAGs. This work is informed by the strands of investigation described above; biologically active GAGs and PGs preparations can be identified, isolated, purified to homogeneity and characterised before being subject to interaction and functional studies.
For example, my previous work has established that the ability of Plasmodium falciparum infected red blood cells to bind to human placenta is modulated by two very specific structural motifs within chondroitin sulphate, one is required for binding but the other actively prevents, rather than simply failing to support, binding.
To have a look at each of the projects in greater details just select one from the list below: