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| Research Domain： |
Chemical Biology |
| Keyword： |
Prof. J.H.P. Bayley |
| Research Production： |
1. Engineering Membrane Channels and Pores
Pore-forming proteins are being engineered for applications in biotechnology. Our main focus is on a-hemolysin, a bacterial toxin that forms a heptameric transmembrane pore of known three-dimensional structure. By using genetic engineering and targeted chemical modification, pores are being made with diverse functional properties. In addition, transmembrane b barrels are being engineered by combining fragments from various bacterial toxins and porins, as well as polypeptide segments designed de novo. The new molecules are finding applications in several areas including drug delivery and the construction of biosensors. These efforts require an excellent basic understanding of membrane protein assembly and function, and we are continuing our work in this area, in particular by using single molecule approaches.
2. High-Throughput Screening with Membrane Proteins
Recent advances have demonstrated that large fractions of prokaryotic and eukaryotic genomes encode membrane proteins. Therefore, there is a pressing need for high-throughput methods to investigate the assembly and functional properties of these polypeptides. By collaborating with laboratories conversant with chip technology, we are developing approaches for the parallel processing of hundreds of membrane samples. Eventually, the approach will yield procedures for refolding membrane proteins and for forming three-dimensional crystals from them. If functional membrane proteins can be obtained on chips, they will be used for high-throughput assays in drug discovery and as a basis for making biosensor arrays.
3. Biomolecular Materials by Design
The design and synthesis of biomolecular materials is a rapidly growing interdisciplinary area, in which the properties of molecules found in nature are mimicked or extended to produce materials with unusual properties. An additional goal is to manufacture and dispose of materials by environmentally benign methods of low energy cost. The heterologous expression of protein-based materials is an attractive option. We are exploring this and related approaches for making materials that form porous sheets, fibers, adhesives and elastomers. For example, we have initiated engineering studies on S layers, the robust porous proteinaceous envelopes that surround many bacterial cells. One goal is to obtain porous monolayers containing molecular switches, for use in biosensors. In another example, we are engineering abductin, a protein found in the highly elastomeric inner hinge ligaments of bivalve mollusks. The project will yield elastomers for use thin films, and in microfluidic and energy storage devices.
4. Caged Peptides and Proteins for Signal Transduction Research
The use of "caged" reagents allows the photogeneration of molecules on or in cells with precise spatial and temporal control. In signal transduction research, effectors and inhibitors can be released at known sites, in defined doses, and at predetermined times. We are using a variety of photoremovable protecting groups to cage peptides and proteins for studies of cell signaling. One tactic has been to derivatize proteins engineered to contain single cysteines at key positions. In this way, a photoactivatable catalytic subunit of protein kinase A has been made. The activities of many cell signaling proteins are modulated by phosphorylation. Therefore, we are also examining peptides and proteins modified on the sulfur atom of thiophosphoryl groups. |
| Remarks： |
Email:hagan.bayley@chem.ox.ac.uk
Telephone:44 (0) 1865 285 100
Chemical Research Laboratory of University of Oxford |
| Original file： |
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