Widening the species range of gene drives for mosquito control

This PhD opportunity is being offered as part of the LSTM and Lancaster University Doctoral Training Partnership. Find out more about the studentships and how to apply

Abstract Genetic insect control is the deliberate introduction of genetic traits into a population, with the goal of reducing its ability to cause harm. In the case of mosquito control these traits can either directly reduce the mosquito's ability to harbour and transmit parasites, or they can negatively affect the mosquito's ability to reproduce, thereby suppressing the population. This type of approach offers a targeted, species-specific form of control and we have demonstrated that we can genetically engineer such traits in the malaria vector Anopheles gambiae. However, a key challenge is how to get these traits into the population since they are unlikely to increase in frequency since they impose a fitness cost on the mosquito. To overcome this we have developed a technology called gene drive which permits the genetic element to copy itself during the process of gamete formation, meaning that it shows strongly biased inheritance among offspring. These gene drive elements can rapidly increase in frequency, despite carrying a fitness cost, and can reach fixation in just a few generations and thus affect the whole population. They therefore represent a self-sustaining, species-specific intervention that is available to all regardless of healthcare access, since the mosquitoes themselves are responsible for delivering the intervention.
If these are to be employed towards malaria elimination it will require that they are developed not just for An gambiae, but for other Anopheles vector species that may be significant vectors in a given area. This project will investigate the feasibility of identifying suitable genetic targets for gene drives in other Anophelines, as well as designing and testing the control elements needed to make these work efficiently in the germline of the new species. Importantly, there will also be a quantitative/modelling aspect to this project that will use the experimental parameters determined for the gene drive to model how likely these new gene drives are to spread in a given ecology and in combination with other conventional interventions.
Where does this project lie in the translational pathway? T1 - Basic Research
Expected Outputs High impact publications in well-cited journals.
Training Opportunities Modelling in collaboration with Target Malaria. Potential industrial placement at Biocentis. Training in molecular biology and cloning at LSTM.
Skills Required An aptitude or strong interest in molecular biology and genetics as well as desire to make mosquito strains that could have a large impact on mosquito and malaria control.

Key Publications associated with this project

doi: 10.1038/nbt.3439
  doi.org/10.1038/nbt.4245
  doi: 10.1093/g3journal/jkab201
  doi: 10.1038/s41467-021-24790-6
  doi.org/10.1371/journal.pgen.1009321