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Title: Reengineering bacterial toxins into virus-like particles
Author: Ross, James Finnian
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2013
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The re-design and controlled self-assembly of natural systems into non-natural functional products is a quickly developing area of Synthetic Biology. Specifically, the manipulation of existing, and the introduction of new protein-protein interactions will allow great advances in bionanotechnology. In nature, protein-protein assemblies mediate many cellular processes and exhibit complex and efficient functions. It is thus rational to assume human-guided biomolecular assemblies could embody equally complex functionality designed to address current human needs. Here we present the design and preparation of a Virus-Like Particle (VLP) engineered from the cholera toxin B-subunit (CTB). This was achieved via the de novo design of a protein-protein interface between CTB subunits consisting of coiled-coil C-terminal extensions and modification to the CTB surface. A combination of computational methods was used to suggest mutations which should reduce the ΔΔG of interaction across the interface. CTB is a natural homopentamer with inbuilt cell targeting and endocytic triggering mechanism. Future applications for the VLP could include use as a drug delivery vehicle to transport protected therapeutic agents to targeted cell types. Through our investigations it became apparent that the CTB-VLP structures behaved in a similar manner to naturally occurring virus coat proteins, which suggests the successful biomimicry of these complex systems. This study provides a basis for the development of further VLPs from other homomultimeric proteins, especially further classes of homopentameric bacterial toxins.
Supervisor: Turnbull, B. ; Paci, E. ; Webb, M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available