| EPSRC Reference: |
EP/C539001/1 |
| Title: |
Synthetic Functionalisation of Glycosaminoglycans for FRET studies. |
| Principal Investigator: |
Hulme, Professor A |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Sch of Chemistry |
| Organisation: |
University of Edinburgh |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 December 2005 |
Ends: |
30 April 2009 |
Value (£): |
222,745
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
Chemical Biology |
| Chemical Synthetic Methodology |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
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| Related Grants: |
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| Panel History: |
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Summary on Grant Application Form |
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Some very important processes in the human body, including blood clotting, and the body's defence against infection, are controlled by how cells respond to signals in the gel-like material that surrounds them, or how they recognise other cells that are their neighbours. These processes can be controlled by the interaction of a particular type of sugar known as a glycosaminoglycan, or GAG for short, with other molecules on the surface of the cell (such as proteins). So cells can recognise each other by the sugar part of one cell sticking to a protein on the surface of another cell.GAGS are actually polymers made up of different sorts of sugars which are linked together, somewhat like a string of coloured beads on a chain. Each bead has a different role to play in the overall shape of the GAG polymer and the proteins on the cell surface will stick more, or less, strongly to any particular sequence of colours. It is thought that GAG polymers might have many different shapes depending on exactly which sugars are linked together, e.g. a helix - as in DNA, or u-shaped - as in a horseshoe. But at the moment there is no way of determining what the shape of each complex polymer actually is, and it is not possible to predict accurately how the GAG polymer and the protein stick to each other. This kind of prediction will help in the design of new drugs.We are going to develop a chemical method to attach a specific label at either end of a short piece of the GAG sugar polymer. Then we will be able to use a new technique called time-resolved fluorescence resonance energy transfer (TR-FRET) to determine how far apart the ends of the GAG polymer are. The TR-FRET technique uses a very short flash of light from a laser to energise ( excite ) the label at one end of the GAG polymer. Then fluorescence occurs, and light of a slightly different colour is given out which excites the label at the other end of the polymer. So overall, energy is transferred from one end of the chain to the other in the form of light. The efficiency of this energy transfer depends very much on how far apart the two labels are. So, by studying very carefully how this energy transfer happens we will be able to say how far apart the ends of the chain are, and if they are fixed relative to each other, or if they are moving about. When we carry out this experiment with a protein present as well, we will be able to explain why the protein and the GAG polymer stick to each other. Once developed, this new approach will allow many different GAG sugar-protein interactions to be investigated.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.ed.ac.uk |