Chemical Biology and Glycomics Strategies for Decoding Heparan Sulfate Structure-Function

Heparan sulphates (HS) are complex sulphated polysaccharides expressed at the cell surface. They are essential co-receptors for many proteins, most notably many signalling growth factors, and they act as dynamic regulators of protein function. Studies on these sugars are at the forefront of the glycobiology field and will be a critical facet of the post-genomic era; “glycomics” (large scale analysis of sugar structure and function) is increasingly important in partnership with proteomics for understanding complex cellular functions. We are actively studying the structure-activity relationships of HS in relation to cell signalling, and development and disease. This project will focus on exploitation of our recent development of a range of novel methods for purification and analysis of HS structures and determination of their functional interactions with cognate proteins such as FGFs in cell signalling. Chemically synthesised glycans will also be exploited in collaboration with partners in Spain, Oxford, and New Zealand. These techniques and resources will be integrated to implement chemical biology and “glycomics” strategies that allow for the first time analysis of larger numbers of HS structures from synthetic chemistry and in vivo (tissue) sources such as brain or skin. Novel information on the structure-activity relationships of HS and the mechanisms by which HS controls protein functions in biological systems contexts will be generated. Techniques used will include: chemical biology; glycomics; glycoarrays & bioarrays; LC-ESMS (mass spectroscopy); cell culture; bioassays; affinity/interaction techniques; HPLC/FPLC chromatography with fluorescence detection.


Training:
Specific practical training will be provided in:
1. Glycobiology (glycan purification; cell culture; bioassays; glycobioarrays)
2. Glycoanalysis (HPLC/FPLC; glycan analysis; ES mass spec sequencing)
3. Glycomics (large scale glycoanalysis; saccharide microarrays; glycobioarrays)
Generic skills training will be provided through:
□ Regular oral presentations of work at group meetings.
□ Producing regular reports where publication quality data are fully analysed and prepared for publication
□ Discussion and criticism of literature at journal club meetings.

Attend national and international meetings and present results (poster/short talk). The student will also potentially be involved lab exchanges with collaborators in the UK, Spain or Sweden.