Understanding the evolutionary space for the development of insecticide resistance

Selection on natural variation in genes that encode the molecular targets of insecticides can lead to the rapid proliferation of alleles that confer insecticide resistance and are selected in wild mosquito populations where insecticide use is the mainstay of mosquito control. This project looks to develop a form of accelerated evolution in vivo, to actively generate as wide a range of target site variants as possible, through the use of CRISPR genome editing tools, active in the germline of the mosquito.

Where does the project lie on the Translational Pathway?

T1 – Basic Research & T2 Human/Clinical Research

Expected Outputs

The project will produce high quality REF returnable 3*/4* publications and will provide the evidence base for large scale research council, philanthropic (e.g. OP and Gates) and industry funding – in particular an industrial partnership award

Training Opportunities

Mosquito transgenesis, embryo microinjection, CRISPR, genome editing, bioinformatics, DNA cloning

Skills Required

Desirable skills to include:- Bioinformatic and/or quantitative biology; molecular biology; aptitude for DNA cloning; nsectary experience; population genetics

Key Publications associated with this project

Kyrou K, Hammond AM, Galizi R, Kranjc N, Burt A, Beaghton AK, Nolan T and Crisanti A A CRISPR-Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes Nature Biotechnology 24 September 2018,

A Hammond, R Galizi, K Kyrou, A Simoni, C Siniscalchi, D Katsanos, M Gribble, D Baker, E Marois, S Russell, A Burt, N Windbichler, A Crisanti and T Nolan. A CRISPR-based Gene Drive System Targeting Female Reproduction in the Malaria Mosquito. Nature Biotechnology 34,78–83 (2016

A Hammond, K Kyrou, M Bruttini, A North, R Galizi, X Karlsson, F Carpi, R D’Aurizio, A Crisanti and T Nolan The dynamics of creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito PLoS Genetics 2017, Oct 9

Hammond AM, Kyrou K, Gribble M, Karlsson, Morianou I, Galizi R, Beaghton AK, Crisanti A and Nolan T Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory contained mosquito populations  bioRxiv (2018) 360339;

Natural diversity of the malaria vector Anopheles gambiae (2017) The Anopheles gambiae 1000 Genomes Consortium.  Nature 552,  96–100 (2017)

LSTM Themes and Topics – Key Words

Malaria and other vector borne diseases; Resistance research and management