Determining drivers of viral community composition in UK mosquitoes and the impact of virome heterogeneity on mosquito competence for arboviruses

Vector-borne pathogens transmitted by mosquitoes include some of the major viral infections of humans such as dengue and zika viruses. Mosquito-borne viruses are a major public health risk. For example, the combined burden of dengue, yellow fever and Japanese encephalitis was >2,000,000 disability-adjusted life years in 2017.

The deployment of Wolbachia-infected Aedes mosquitoes to successfully reduce dengue incidence has brought attention to the importance of understanding how viruses and bacteria naturally infecting mosquitoes influence their potential to transmit human-infective pathogens. The community of viruses within a mosquito; termed the ‘virome’ may not only provide a new source of control options in the long-term, but heterogeneity in the virome of mosquitoes may explain spatial variation in vector competence and thus variation in arbovirus outbreak risk. However, the drivers of spatial variation in the virome of mosquitoes are currently unknown. This project will characterise the virome of Aedes detritus and Culex spp from the Wirral, UK using minION and Illumina sequencing. Resulting data will be used to determine variation between and within populations of mosquitoes by land cover type and life history stage. Next steps will include the assessment of the impact of the mosquito virome on the ability of mosquitoes to become infected by, and transmit, arboviruses.

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 the supervisor team 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 a programmer in industry.

 

There is clear scope for translational impact, and there is a strong drive for more virus-focused funding calls both from national (in particular UKRI-BBSRC) and international funders, evidenced amongst others by the recent formation of a Pandemic Preparedness Institute, where LSTM, including JL, is heavily involved. Targeting vector-borne viral disease is a key strategic area for LSTM as evidenced by JL who was awarded the inaugural highly prestigious Janet-Hemingway-Fellowship and is on the Career Track scheme; EH who was recruited from the Wellcome Sanger Institute and was confirmed for tenure in the first year of her Career Track followed by promotion to Senior Lecturer, and TE who was recently promoted to join the Career Track scheme.

Training Opportunities

The student will receive a highly sought-after combination of skills in i) bioinformatics, including comparative genomics and molecular evolution and accompanying laboratory-based in-depth insights into different sequencing techniques; ii) molecular biology, in particular insect culturing, virology and work on containment level three; and iii) epidemiology, in particular geospatial understanding of host-virus dynamics and planning an informed sampling frame for field collections, as well as mathematical modelling of vector competence depending on their innate virome.

Skills Required

Basic knowledge of and strong interest in vector biology, virology and bioinformatics.

Key Publications associated with this project

Patterson et al. (2021). Negeviruses reduce replication of alphaviruses during coinfection. Journal of Virology. 95(14): e0043321. https://doi.org/10.1128/JVI.00433-21

Lord and Bonsall (2021). The evolutionary dynamics of viruses: virion release strategies, time delays and fitness minima. Virus Evolution. 7(1): veab039.  https://doi.org/10.1093/ve/veab039

Maklin et al. (in press). Bacterial genomic epidemiology with mixed samples. Microbial Genomics.

Walker et al. (2021). Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes. Current Biology. 31(11):2310-2320. doi: 10.1016/j.cub.2021.03.056.

Fletcher (2021). Characterising the virome of UK Aedes detritus: method comparison of cDNA production prior to MinION sequencing. Tropical Disease Biology MSc Thesis. LSTM.

LSTM Themes and Topics – Key Words

Neglected Tropical Diseases, Malaria & other Vector Borne Diseases, Resistance Research & Management

Now Accepting Applications 

CLOSING DATE FOR APPLICATIONS: Application Portal closes: Wednesday 9th February 2022 (12:00 noon UK time)

Shortlisting complete by: End Feb/early March 2022

Interviews by: Late March/early April 2022

For more information on Eligibility, funding and how to apply please visit the MRC DTP/CASE pages