GENERAL RESEARCH GOALS
Research focussed in health care and environmental management. Though these are very disparate fields, the problems tackled are linked in that they focus on protein engineering with antibodies as the paradigm, and design and use novel combinatorial libraries to select and evolve new proteins with higher affinity for their targets, improved stability, and ease of production.
Particular goals were:
to provide novel binding proteins with affinities for their targets which are much higher than those provided by traditional monoclonals through the use of antibody phage display libraries and combinatorial libraries based upon novel scaffolds.
to design antibody fragment configurations with improved solubility, thermal, proteolytic resistance, and stability in organic solvents and detergents.
to provide methods for manufacture of antibody fragments on a scale, and at a cost acceptable for application in environmental management and as components of topical pharmaceuticals, cosmeceuticals or consumer goods.
These challenges were tackled using a variety of genetic and protein engineering techniques and the construction and design of combinatorial libraries. Immunotechnologies, BiaCore biosensor analysis and computer modelling were used extensively. The aims of the research were successfully completed and are overviewed in the publication: “Exploiting Antibody based Technologies in the Management of Environmental Pollution” (1999). Harris, W. J. Trends in Biotechnology. 17, 290-296.
Projects in Detail
ANTIBODY ENGINEERING AND COMBINATORIAL
LIBRARIES.
Humanization of antibodies by our fixed framework method (In : Antibody Engineering, 1995, Ed. C Borrebaeck, Oxford Press 159-183), selection of phage antibodies from combinatorial libraries, and configuration of antibody fragments for topical or mucosal delivery, formed the basis of collaborative research programmes related to providing short term protection against Yersinia pestis and Venezualan equine encephalitis virus and discovery research of the autoimmune diseases posterior uveitis and multiple sclerosis.
Phage antibody display libraries derived from sheep have been developed to provide
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