Disentangling interactions between the mosquito and its microbiome

Abstract

Given the rise of insecticide resistance and the invasion of vectors into new areas in the course of climate change and urbanisation; new, alternative approaches to vector control are urgently needed. Ideal control measures can be used in conjunction with already existing ones to avoid reliance on one single method, which renders the system inflexible and control failure has dramatic consequences until a replacement is found.

An attractive approach is the use of mosquito-associated bacteria as delivery vehicles for toxins or other modifying traits; which can lead to death of the mosquito, blocking of arboviral infection, or reducing the mosquito lifespan. However, whilst a large body of work is ongoing to find the delivered toxins or other genetic manipulation methods; we still have very limited understanding of the bacteria inhabiting the midgut; which however are one of the two essential components, i.e. the delivery vehicle of the trait of interest. In addition, recent publications highlighted again the relevance of screening members of the microbiome for toxic molecules they might express naturally that can block arboviral or parasite infection and thus transmission via the mosquitoes.

This PhD proposal will be embedded in the closely interlinked teams of Grant Hughes (GLH; mosquito microbiomes) and Eva Heinz (EH; microbial genomics), and address the ability of bacteria to colonize the mosquito with a focus on the bacterial cell surface and how bacteria establish themselves as stable symbionts. The other highly relevant part of the project will be to screen our existing, already sequenced, collection of ~500 bacterial isolates derived from mosquito midguts, for toxins and establish whether any molecules could be candidates for blocking arboviruses or pathogens.

This project will be placed in the collaborative work between EH and GLH, which includes a five-year funded BBSRC-NSF grant, where this position will use mosquito midgut-derived whole-genome sequence data generated in the course of this larger project, and focus on the diversity and evolution of surface protein families as well as the relevance of cell surface polysaccharides in the ability of bacteria to colonize the mosquito host.

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 essential data for translational follow-up work on using microbes to control arboviral vectors. Previous and current PhD students from the team have all published high-quality first-author publications, and have moved to postdoctoral positions or are working as programmer in industry. Recent work from EH and GLH on mosquito microbiomes has resulted in high-quality publications in Current Biology, the ISME Journal, PLoS Pathogens and PLoS NTD. The project will have the unique opportunity to access large-scale sequence data from mosquito-derived symbionts which has been generated in the course of a shared 5-year BBSRC/NSF-funded project by EH, GLH and Dr. Kerri Coon (USA).

Given EH placement at KEMRI Kisumu, there is clear potential to expand the work in collaboration with the large mosquito research programs on Kisumu campus.

Training Opportunities

Training will be provided in bioinformatics (molecular evolution, comparative genomics, host-pathogen interaction, protein family evolution), evolutionary models (EH); insectary work, cell culture and molecular techniques (GLH). The student will furthermore be embedded in the already closely collaborating network between the supervisory team and further collaborators world-wide.

Skills Required

The student should be interested in working with mosquitoes and in microbial genome evolution, host-microbe interactions, and co-evolution.

Key Publications associated with this project

Foo et al. 2023 Wellcome Open;  Recovery of metagenomic data from the Aedes aegypti microbiome using a reproducible snakemake pipeline: MINUUR

Hegde et al. 2023 bioRXiv  Aedes aegypti gut transcriptomes respond differently to microbiome transplants from field-caught or laboratory-reared mosquitoes.

Kozlova et al. 2020 ISME Journal; Microbial interactions in the mosquito gut determine Serratia colonization and blood-feeding propensity.

Hegde et al. 2019 PLoS NTD; CRISPR/Cas9-mediated gene deletion of the ompA gene in symbiotic Cedecea neteri impairs biofilm formation and reduces gut colonization of Aedes aegypti mosquitoes