The 2024/25 application process is now CLOSED
Visit the MRC DTP/CASE at LSTM pages for further information.
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Abstract |
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. Given the variety and heterogeneity of these new selection pressures, evolution is likely to be occurring at multiple loci, many of which may be unknown, throughout the genomes of malaria vector species. The availability of data from the Anopheles genomes project (Ag1000G) on genetic variation in thousands of wild-caught malaria vectors provides a unique opportunity to study the full genomic landscape of recent selection, to discover new adaptations to insecticide resistance, and to compare the genomic profile of adaptation between different species and populations. Of the many selection signals identified, several of these mapped to loci known previously to be involved in target-site and metabolic resistance to insecticides, confirming the validity of the approach. Interestingly though other selection signals mapped to genes whose function is difficult to reconcile with metabolic turnover of insecticide or with being direct target sites of insecticides. One such gene, which is the focus for this project, may have roles in either altered synaptic transmission of nerve signals or, potentially, altered visual signalling, which may point to altered behaviour that ultimately leads to less insecticide exposure To this end the ability to recreate, on a standardised genetic background, different alleles of genes observed in the wild and assay their contribution to insecticide resistance and behaviour in the laboratory is 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 novel genetic signals of selection and then design and test genetic constructs for integration into a standard mosquito strain to recapitulate and measure their effect on mosquito behaviour. |
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Where does the project lie on the Translational Pathway? |
T1 – Basic Research T3 Evidence into Practice |
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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 |
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Training Opportunities |
Training in DNA cloning, genotyping, presenting data, data analysis, report and project writing |
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Skills Required |
A good grounding in molecular biology and/or genetics |
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Key Publications associated with this project |
Anopheles gambiae 1000 Genomes Consortium et al. 2017 (doi: 10.1038/nature24995) |
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Grigoraki et al 2021 ( doi.org/10.1371/journal.pgen.1009556) |
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Clarkson et al. 2021 ( doi.org/10.1111/mec.15845) |
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