Opening up Anopheles funestus to functional genetics and the study of insecticide resistance

The study of the genetic basis of insecticide resistance in the important malaria vector Anopheles has lagged, due to a paucity of available expertise in rearing this mosquito and the resultant lack of genetic variation on which to select for traits of interest. Regions of the funestus genome associated with insecticide resistance have been identified yet the inability to easily rear and cross wild caught strains in the lab drastically limits the power and resolution to identify candidate genes that may be determining resistance, let alone identify the specific mutations that constitute a resistant allele. This not only precludes a full mechanistic understanding of the basis of resistance, it is an obstacle to developing molecular genotyping assays to detect resistance without the need to always do insecticide resistance assays in the field, which can be noisy, slow and logistically challenging. The boon of CRISPR-mediated genome editing holds much promise for introducing alleles of choice into a given genetic background. Our groups have pioneered its use in the malaria vector Anopheles gambiae, and are starting to use it to decipher insecticide resistance in that species. However, there is a large and growing body of evidence that mechanisms of resistance have evolved very differently in these two species that are separated by ~30 million years of evolution, not only at the level of target gene families but also in the predominant mechanisms of rendering insecticides ineffective. This includes preliminary data that shows a developed CRISPR pipeline that can recapitulate insecticide resistance alleles, normally found in the field, on the standardised An. funestus lab background. Now that the technology has been developed and proven the generation of a series of putative resistance alleles have been planned to understand their effect size, their mechanism of action and their interaction with other resistance mechanisms and their fitness effect.

External Reference Name

Insecticide Resistance

Oct 2023 — Oct 2026

$703,794

United Kingdom