From Fertility to Feeding: Identifying New Gene Drive Targets in Malaria Vectors

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 Whilst significant progress has been made in the control of global malaria burden, this is now threatened in part due to the development of insecticide resistance in the vector mosquitoes. This means that malaria is still a significant global health threat, with people from Low- and Middle-Income Countries and children under 5 at highest risk. The increasing burden of malaria incidence over recent years highlights the need for new and novel vector control strategies, such as genetic control. Genetic vector control uses gene editing technologies with the aim of modifying or reducing the wild vector population. Our group uses a technique known as gene drive to bias the inheritance of these edited genetic elements to enable more rapid spread of the desired gene edit and ultimately a faster modification or reduction in the target population. Our previous and current work uses gene drives to target female fertility genes, insecticide resistance genes and those involved in bloodmeal metabolism. However, there are a number of factors that make Anopheles mosquitoes efficient vectors of malaria including longevity, host feeding behaviour, habitat preference and susceptibility to the parasite. All of these characteristics are at least in part genetic, meaning there is ample availability of genetic targets for vector control. This project will therefore look to identify new genetic targets for modification such as those involved in mosquito oviposition or blood feeding, accessing the feasibility of targeting these genes using CRISPR editing with the aim of generating new transgenic Anopheles lines with alternative target sites for population modification or suppression. Once appropriate target sites have been identified, gene drives will be introduced using a CRISPR system and resulting transgenic lines characterised.
Where does this project lie in the translational pathway? T1 - Basic Research,T3 - Evidence into Practice
Methodological Aspects
  • Bioinformatics skills to identify target regions
  • Molecular biology and cloning
  • CRISPR genome editing
  • Embryo microinjection and generation of transgenic mosquito lines
  • Characterisation of transgenic lines.
  • Cross and cage based population simulations.
  • Modelling gene drives
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 a global priority area. the development of an international profile in mosquito genetics and gene drive research; transferable personal skills to industry and/or academia
Training Opportunities
  • CRISPR genome editing
  • DNA cloning and molecular biology techniques
  • Execution of large cage studies
  • Bioinformatics
  • Insect husbandry
  • Professional development course
  • Data analysis and presentation
  • Publication and report writing
Skills Required
  • A good general understanding of genetics
  • An aptitude for molecular biology, genetics and vector control.
Subject Areas Malaria and other Vector Borne Diseases
Key Publications associated with this project

Gantz, V.M. and Bier, E., 2022. Active genetics comes alive: Exploring the broad applications of CRISPR‐based selfish genetic elements (or gene‐drives). Bioessays, 44(8), p.2100279.

Naidoo, K. and Oliver, S.V., 2025. Gene drives: an alternative approach to malaria control?. Gene Therapy, 32(1), pp.25-37.

Hammond, A., Galizi, R., Kyrou, K., Simoni, A., Siniscalchi, C., Katsanos, D., Gribble, M., Baker, D., Marois, E., Russell, S. and Burt, A., 2016. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nature biotechnology, 34(1), pp.78-83.