Investigating the Role of Copy Number Variation in Insecticide Resistance

Huge successes in reducing the malaria burden haven been achieved over the last 20 years, predominantly due to deployment of the effective combination of insecticides and bednets as a method of mosquito control. Duplication of genes and genomic regions is a major source of evolutionary novelty and is increasingly recognised as a key component of adaptive response. Genes or segments of genomes that show copy number variation (CNV) between insects are a rich source of potentially adaptive polymorphism which may help overcome the constraints of purifying selection on conserved genes and/or permit elevated transcription. We have recently shown that CNV can influence insecticide resistance and that some types of CNV appear to be under positive selection in areas where insecticide use is high. Our findings were based on data from genome sequencing of mosquitoes caught in the field. However, not all CNVs detected in the genomes of field-caught mosquitoes are expected to confer resistance and their increasing incidence may, in part, reflect advances in our methods and ability to detect it. Being able to distinguish between CNVs that are causative, as opposed to incidental, to insecticide resistance is essential if we are to improve our ability to use genotyping methods to detect insecticide resistance in the field and to change vector control approach or insecticide class accordingly.

To this end the ability to recreate, on a standardised genetic background, different CNVs identified from the wild and assay their contribution to insecticide resistance would be game changing. We have developed a suite of genome editing tools based on CRISPR that allow us to introduce, with high efficiency, genetic mutations of choice precisely into the mosquito genome. This project will thus integrate information emerging from the field on the prevalence of CNVs and then design and test genetic constructs for integration into a standard mosquito strain to recapitulate the effect of the CNV.

Where does the project lie on the Translational Pathway?

T1 (Basic Research) – T3 (Evidence into Practice)

Expected Outputs

An improved understanding of the genetics of insecticide resistance; improved operational outcomes in vector control programs due to better screening for insecticide resistance; peer-reviewed publications in quality scientific journals; the development of an international profile in mosquito genetics and insecticide resistance; transferable personal skills to industry and/or academia

Training Opportunities

Training in DNA cloning, genotyping, presenting data, data analysis, report and project writing

Skills Required

A good grounding in molecular biology and/or genetics

Key Publications associated with this project

Lucas et al. 2019 ( doi:10.1101/gr.245795.118)

Grigoraki et al 2021 ( doi.org/10.1371/journal.pgen.1009556)

Clarkson et al. 2021 ( doi.org/10.1111/mec.15845)

LSTM Themes and Topics – Key Words

Malaria and other Vector-borne diseases