Exploiting native Wolbachia strains in Anopheles mosquitoes for novel malaria control approaches.

The 2024/25 application process is now CLOSED

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Abstract

Despite an intense control effort, malaria continues to be a major public health challenge, particularly in sub-Saharan Africa. Promisingly, new vector control strategies are being developed such as microbial and genetic control approaches. While Wolbachia-based control has been effective in Aedes mosquitoes, the use of this bacterium is more challenging in Anopheles mosquitoes.  However, recently, we have found two Wolbachia strains that naturally infect Anopheles mosquitoes, and these strains are promising candidates for control in other medically relevant Anopheles vectors. Wolbachia is desirable for control given in can manipulate the reproduction of its host. One common manipulation is cytoplasmic incompatibility, which enables Wolbachia to spread into insect populations. The mechanisms by which Wolbachia exerts CI has recently been elucidated, with the Cif genes implicated in the phenotype. This project will examine the functionality of Cif genes in the two Wolbachia strains that infect Anopheles. To do this the project will involve creating transgenic mosquitoes expressing these bacterial genes, and characterising the  capacity of these constructs to induce CI, to spread into mosquito populations as a form of gene drive, and to suppress population reminiscent of population suppression approaches. Data acquired from these cage experiments can then be used to model the effectiveness of Cif based gene drive approaches. The findings from this work will be instrumental in developing Wolbachia-based microbial control or transgenic Cif-based approaches to control Anopheles mosquitoes.

 

Where does the project lie on the Translational Pathway?

T1 – Basic 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 funding in a global priority area. Previous and current PhD students from GLH, and TN have all published one or several high-quality first author papers, and have all moved to postdoctoral positions, head of regional vector control programmes or government bodies or are working in industry.

Training Opportunities
  • Courses using R to examining big data sets.
  • Molecular biology training
  • Training for embryo microinjections techniques.
  • Modelling

Skills Required
  • A general understanding of either vector biology, genetics, and/or synthetic biology

Key Publications associated with this project

Walker T, Quek S, Jeffries CL, Bandibabone J, Dhokiya V, Bamou R, Krisan M, Messenger LA, Gidley A, Harbach RE, Hornett EA, Anderson ER, Cansado-Utrilla C, Hegde S, Bantuzeko C, Stevenson JC, Lolo NF, Wagstaff SC, Heinz E, Antonio-Nkondjio C, Irish SR, Hughes GL (2021). Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes Current Biology. 31, 1-11

Hughes GL, Dodson BL, Johnson RM*, Murdock CC, Tsujimoto H, Suzuki Y, Patt AA*, Cui L*, Nossa CW, Barry RM*, Sakamoto JM, Hornett EA, Rasgon JL. (2014) Native microbiome impedes vertical transmission of Wolbachia in Anopheles mosquitoes. Proceedings of the National Academy of Sciences USA. 111 (34): 12498-12503.