Exploring control of arboviral disease using Wolbachia in Aedes aegypti formosus

Arboviral diseases cause significant global mortality and morbidity, and the incidence of disease is forecast to increase further due to global change. The main vector of viruses to humans is the mosquito, Aedes aegypti, which includes two subspecies, Aedes aegypti aegypti and Aedes aegypti formosus. The former is a highly effect vector that is intimately associated with humans, while the latter is a forest dwelling mosquito that is important for the sylvatic cycle of viruses. While Wolbachia control strategies in Aedes aegypti aegypti have been demonstrated to be highly effective at controlling dengue virus in humans, little attention has been paid to Wolbachia control of Aedes aegypti formosus. This project will investigate the use of Wolbachia to control viral transmission and spill over in Aedes aegypti formosus. The project will explore the ability to infect Aedes aegypti formosus with Wolbachia and characterise the infection by next generation sequencing and microscopy-based approaches, examine viral blocking in the mosquito, and characterise reproductive manipulations in this mosquito. The project will take the first steps towards using Wolbachia control to virus transmission in Aedes aegypti formosus. 

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 EH have all published one or several high-quality first-author papers, including Molecular Microbiology, PLoS Pathogens, Microbial Genomics and Nucleic Acids Research, and have all moved to postdoctoral positions or are working as programmer in industry. Recent work from GLH and EH on collaborative projects have resulted in several high-impact publications, including ISMEJ and Current Biology. The project will have the unique opportunity to work on highly relevant questions to the arguably currently most promising vector control tool against Dengue virus, and development of a Wolbachia infected Aedes aegypti formosus line will be a highly valued resource and desirable for funding agencies. In addition, the student will be embedded in a larger collaborative network on Wolbachia-mosquito interactions, which included Dr Tom Walker (LSHTM), Dr Frank Jiggins (University of Cambridge), Dr Antonio Nkondjio (OCEAC, Cameroon).

Training Opportunities

Vector biology, virology, high containment training, bioinformatics.

Skills Required

General vector biology and bioinformatics background

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.

Khoo JJ, Kurtti TJ, Nurul Aini Husin NA, Beliavskaia A, Zulkifli MMS, Al-Khafaji A, Hartley C, Darby AC, Hughes GL, AbuBakar S, Makepeace BL, Bell-Sakyi L (2020) Isolation and propagation of laboratory strains and a novel flea-derived field strain of Wolbachia in tick cell lines. Microorganisms. 8(7): 988.

Etebari K, Hedge S*, Saldaña MA*, Widen SG, Wood TG, Thangamani S, Asgari S, Hughes GL. (2017) Global transcriptome analysis of Aedes aegypti mosquitoes in response to Zika virus infection. mSphere. 6 (2): 300456-17.

Quek S, Cerderia L, Jefferies CL, Tomlinson S, Walker T, Hughes GL, Heinz E (2021). Wolbachia endosymbionts in two Anopheles species indicates independente acquisition and lack of prophage elements. BioRxiv.

LSTM Themes and Topics – Key Words

Resistance Research & Management, Malaria & other vector-borne disease, Neglected Tropical Disease.