EASTBIO InsPeC: a novel and sustainable method to control insect pests and disease vectors.

Supervisors:

Dr Juliano Morimoto (University of Aberdeen)
www.jmorimoto.com

Dr Andrew Quigley (Diamond Light Source)
https://www.diamond.ac.uk/Instruments/Mx/MPL.html

Dr Jelena Baranovic (University of Edinburgh)
https://orcid.org/0000-0003-2310-960X

Dr Wael Houssen (University of Aberdeen)
https://www.abdn.ac.uk/people/w.houssen

This project aims to change the way pest control is done, making it more efficient, specific and sustainable.

Insect pests of agriculture, like the spotted-wing Drosophila suzukii, can inflict an annual cost of £65 billion to worldwide economy, an estimate that is higher if livestock pests (e.g., sheep blowfly) are included. Moreover, according to World Health Organization (WHO), 700,000 deaths every year are attributed to diseases transmitted by insects, mostly mosquitoes (aka ‘insect vectors’), with almost 4 billion people at risk of having Dengue fever [1]. These staggering numbers show that current approaches to control insect pests and vectors are failing. But how can we do better?

Insect pests and vectors have, in their cells, membrane proteins that are activated by peptides hormones. Once activated, these membrane proteins communicate that ‘it’s time to produce and lay eggs.’ In response, insects change their behaviour to eat more protein (needed to produce eggs) and search sites to lay eggs. These behavioural changes that lead vectors to feed on blood (i.e., protein source) and pests to lay eggs on fruits and crops. If we can stop these messages, we can in theory create a robust way to significantly decrease or abolish pests’ outbreaks and disease transmission.

InsPeC (Insect peptide control) combines structural biology, drug design, and entomology to achieve this in practice.

Research training and skill development
The first part of the project involves cloning, expression, and crystallisation (and/or cryoEM) of the membrane proteins and their natural hormones. This will allow for the 3D atomic structure of the membrane protein and their hormones, separately and together, to be resolved, providing atomic resolution information on how hormones bind and activate the membrane proteins. Biophysical characterisation of this binding will also be achieved through the 3D structure and supplementary techniques (e.g., FTIR). The candidate will be trained both at the University of Aberdeen and at Diamond Light Source on techniques including PCR, RF-LIC cloning, protein purification and crystallisation (e.g., sitting and hanging drop methods). Protein expression (both in bacteria and insect cells) will provide the candidate with expertise in cell culture.

The second part of the project involves computational biology, where the candidate will gain expertise on molecular simulations and ‘drug design’. Using the structural information above, the candidate will design synthetic peptides similar to natural hormones in structure but that bind and inactivate the membrane proteins. These synthetic peptides will block the membrane protein messages that change insect behaviour thereby stopping blood feeding (vectors) and oviposition in fruits and crops (pests).

InsPeC uses Drosophila melanogaster as model organism, for which most molecular tools are readily available, to develop a proof-of-principle for the concept. This proof-of-principle is readily patentable and transferable to other insects, including medflies and other tephritid pests, spotted- wing D. suzukii, blowflies, tsetse flies and mosquitoes. InsPeC can revolutionise the future of insect management.

Summary of skills and training
Bioinformatics;
Cryo-EM/X-Ray Diffraction,
Molecular biology;
Experimental design;
Cell culture;
Storytelling with Data

Application Procedure:

http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts to Alison McLeod at [Email Address Removed]. Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to [Email Address Removed].