| EPSRC Reference: |
EP/C530187/1 |
| Title: |
Determination of structure and composition via an optical analog of 2D NMR: Optical Fingerprinting of Complex Biomolecules and Molecular Mixtures |
| Principal Investigator: |
Klug, Professor DR |
| Other Investigators: |
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| Department: |
Chemistry |
| Organisation: |
Imperial College London |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 March 2005 |
Ends: |
30 November 2008 |
Value (£): |
563,590
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| EPSRC Research Topic Classifications: |
| Chemical Structure |
Genomics |
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Summary on Grant Application Form |
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In the future, medicine and therapeutic drugs will be tailored to the individual rather than prescribed generically. In order to make this possible we will have to revolutionise our ability to diagnose individual medical problems and to accurately asses the biochemical state of an individual.Proteomics is the label usually given to attempts to analyse some of the -100,000 proteins present in an individual cell. This information, if it were possible to obtain it, would transform our ability to study the effects of new drugs, to design new drugs, and to diagnose medical problems.The most important factors in such a diagnosis are the levels of particular proteins in specific cells, and the exact chemcial state of these proteins. Unfortunately many of the most important proteins are present in low abundance. There is also no generic high throughput way to identify large numbers of proteins reliably and certainly not to determine their chemical state. The chemical state, such as whether particular amino acids have been phosphorytated or not, often controls whether the protein is in an active state or not, and therefore just knowing the levels of a particular protein is often insufficient.The most precise and information rich method currently available is NMR. However NMR takes many hours to obtain the data for a single protein. Current high throughput methods such as mass spectrometry are not able to determine phophorylation levels reliably or identify many types of protein well and are still insufficiently high throughput and insufficiently quantitative to be useful in diagnosis.Optical analogues of NMR exist which have similar chemical sensitivity and data content to NMR, but are much more sensitive and are potentially high throuput. These optical methods work by measuring vibration-vibration coupling and are therefore sensitive to chemical structure and compostion. We have shown in a pilot study that one such method has great potential to be used for protein analysis in a way useful to aid proteomic analysis.In this project we will improve optical 2D fingerprinting methods to the point at which they are a useful tool for studying proteins and the chemical state of proteins. This involves studying the molecular dynamics that go to make an optical fingerprinting and predicting the fingerprints of proteins. By comparing these with measured fingerprints we will start to gain a clearer understanding of how to make reliable definitive fingerprints and also examine whether the method may be helpful in analysing the structure of proteins and reactive intermediates in biological catalysis.
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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.imperial.ac.uk |