Supervisors: Dr Janice Bramham, Dr Alan Bowman
Project Description:
This project will explore a potential strategy for the control of insect pests that is target-specific and eco–friendly. It proposes to determine whether gene silencing by RNA interference (RNAi) can be used as a tool for pest management by focussing upon a biological pathway in insects that has been identified as essential for successful reproduction. The proposed project has potential for a wide impact as it could be applied to many oviparous pests with specificity, for example disease-carrying insects such as mosquitos; major crop pests; and parasitic insects such as bee mites.
Vitellogenesis is the vital process of nutrient provision for oviparous animals. Vitellogenin (Vg) is the precursor of the major yolk protein vitellin which provides the raw materials for early development of the embryos: its entry into oocytes is mediated by its cognate receptor, VgR. Its fundamental role in reproduction makes vitellogenesis an attractive target for pest control. Our hypothesis is that interfering with this critical pathway will adversely affect embryonic development, thereby significantly reducing the fecundity of the pest, resulting in overall decrease in the population.
The specific molecular details for the interaction between Vg and VgR are ill-defined. Therefore, the research will employ a biophysical and structural approach to obtain atomic-level structural data of Vg and VgR from numerous insects, to characterise their properties and to investigate specific intra-, and intermolecular interactions at the domain level in order to fully understand the interaction. Structure-guided, site-directed mutagenesis will be employed to confirm the functional importance of specific residues and interactions revealed by the structural work. In parallel, RNAi will be performed to knock down VgR in specific insects and/or parasite and to evaluate the effect on oocyte development, in order to validate the essentiality of the interaction in vivo, to test for specificity and, ultimately, to assess the feasibility of this gene-knockdown approach for pest control.
The student will receive interdisciplinary training with that for the recombinant protein work being primarily in Edinburgh and for the RNAi/insect work being primarily in Aberdeen. Early in the project, training will be in bioinformatics, molecular biology and recombinant protein technology, in order to design, construct, over-express and purify recombinant proteins from various expression systems. The student will also be trained in a range of biophysical techniques, including high-resolution NMR and/or crystallography, mass spectrometry, light scattering, circular dichroism and isothermal titration calorimetry. Further training will develop skills with insect cell culture and RNAi.
Both the universities of Edinburgh and Aberdeen have excellent infrastructure, state-of-the-art equipment and expertise for this project.
The student will have access to all the PhD training programmes including journal clubs, method clubs, scientific writing skills and presentation skills.
Receptor-ligand interaction between vitellogenin receptor (VtgR) and vitellogenin (Vtg), implications on low density lipoprotein receptor and apolipoprotein B/E.(2003) Li et al. J Biol Chem. 278, 2799-806.
The first vitellogenin receptor from a Lepidopteran insect: molecular characterization, expression patterns and RNA interference analysis. (2011) Shu et al. Insect Mol. Biol. 20, 61-73.
Gene-knockdown in the honey bee mite Varroa destructor by a non-invasive approach: studies on a glutathione S-transferase. (2010) Campbell et al. Parasites & Vectors, 3:73.
If you wish to apply for this project, please go this link.
