Project No. 2350

Primary Supervisor

Prof Vincent O’Connor – University of Southampton

Co-Supervisor(s)

Dr James Dillon – University of Southampton

Marcus Guest – Syngenta (Industry partner)

Summary

An important goal for the future development of crop protection strategies is selective targeting of pest species over non-pest species.

Biologics based on protein architectures offer a potential route to perturb biological function. The development of antibody technologies that disrupt molecules is an attractive approach. Conventional antibodies are oligomeric proteins with complex biogenesis. However, the relatively large size of antibodies restricts tissue access and penetration to target sites. In this proposal, we will investigate nanobodies: single chain simple polypeptide equivalents of the antibody variable heavy chain. These have epitope specificity to selectively target molecules and execute functional perturbation. The nanobodies have simplified recombinant expression and provide interfering technologies readily introduced into biological systems by transgenic approaches. We propose experiments designed to translate nanobody technology by taking advantage of the experimental tractability of C. elegans.

We will develop bioinformatics pipeline to identify candidate molecular targets that are in tissue that are accessible to nanobody perturbation.

We will use transgenic approaches to generate tagged versions of the selected target molecules expressed at physiological levels to assess nanobody binding in vivo.

We will use established phenotypes that have well known molecular determinants to allow us to score efficacy of nanobody binding to disrupt in vivo biology. This is aimed at affording routes to developing nanobody technologies for nematode pest mitigation and food security.