Last Updated: 29/09/2025
Investigating the genetic basis of putative behavioural mechanisms of insecticide resistance in the malaria mosquito
Objectives
The goal of this project is to uncover and experimentally validate novel genetic mechanisms that enable malaria-transmitting mosquitoes to survive insecticide exposure, including those that may alter mosquito behaviour rather than just metabolic or target-site resistance.
Liverpool School of Tropical Medicine (LSTM), United Kingdom
Huge successes in reducing the malaria burden have 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.
Given the variety and heterogeneity of these new selection pressures, evolution is likely occurring at multiple loci—many of which may be unknown—throughout the genomes of malaria vector species. Data from the Anopheles Genomes Project (Ag1000G) on genetic variation in thousands of wild-caught malaria vectors provide a unique opportunity to study the full genomic landscape of recent selection, discover new adaptations to insecticide resistance, and compare the genomic characteristics of adaptation between different species and populations. Among the many selection signals recognized, several mapped to loci previously known to be involved in target-site and metabolic resistance to insecticides, validating the approach. Interestingly, other selection signals mapped to genes whose functions are difficult to reconcile with metabolic turnover of insecticide or with being direct target sites of insecticides. One such gene, the focus of this project, may influence either altered synaptic transmission of nerve signals or altered visual signalling, potentially pointing to behavioural changes that ultimately reduce insecticide exposure.
To address this, the ability to recreate, on a standardised genetic background, different alleles of genes observed in the wild and to assay their contribution to insecticide resistance and behaviour in the laboratory is transformative. A suite of CRISPR-based genome-editing tools has been developed to introduce, with high precision, genetic mutations of choice into the mosquito genome. This project will integrate information on the prevalence of novel genetic signals of selection, then design and test genetic constructs for integration into a standard mosquito strain to recapitulate and measure their effects on mosquito behaviour.
Sep 2024 — Sep 2028
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