Structural analysis of insecticidal proteins
Applicants (UK, EU and international) capable of self-funding or with scholarship are welcome to apply.
Principal Supervisor: Dr Colin Berry, BIOSI
2nd Supervisor: Prof Tim Wess, OPTOM
Industrial Supervisor: Dr Ken Narva, DAS
Bacillus thuringiensis strains produce insecticidal proteins that make the bacteria suitable for use in the biological control of insect pests of crops and insect vectors of human disease. Transgenic plants expressing these proteins have also been developed to confer insect resistance and these are widely-used in the field. Many of these insecticidal proteins belong to a so-called “three-domain family” of toxins and our understanding of their mechanism of action is well-advanced and has been aided by our knowledge of their 3‑dimernsional structures. However, an increasing number of insecticidal toxins is being discovered that are unrelated to this family and we have no knowledge of their structure or how this may contribute to their activity and insect specificity. In collaboration with an industrial partner we aim to undertake the characterisation of these atypical toxins and study their structure and function relationships. Structural analysis will involve the use of circular dichroism to estimate secondary structure composition and Small Angle X‑ray Scattering (SAXS) to determine the topology of the proteins. The quaternary structure of toxins in solution will be assessed using a range of techniques such as analytical ultracentrifugation, size exclusion chromatography, fluorescence tumbling or surface plasmon resonance. For some toxins we will also establish crystallisation trials. Functional studies will assess the effect of mutations, deletions and the construction of chimeric proteins on insecticidal activity. Using the information gathered we will relate structure to function. The insights gained will allow us to undertake the redesign of the toxins to target different insect species in the future. The student will be trained in techniques of microbiology, protein biochemistry, molecular biology and structural analysis.