Exploiting antivirals for control of arboviruses in mosquitoes.

Abstract

Arboviral diseases cause significant global mortality and morbidity, and the incidence of disease is forecast to increase further due to global change. As such, novel approaches are required to reduce the burden of disease. Exploiting mosquito behaviour for the delivery of desirable chemicals is a novel approach for targeted vector control. Recent findings suggest mosquitoes are attracted to specific colours and surfaces which could act as conduits for antiviral molecules. The use of an antiviral has several advantages over conventional insecticide chemistries, which kill the insect, in that they are safe and specific approaches which should mitigate the emergence of resistance in the mosquito. Here the candidate will have the opportunity to explore questions spanning a range of topic for developing antivirals for control of arboviruses in mosquitoes including; 1) explore the efficacy of antiviral molecules and synergistic interactions between chemistries, 2) explore natural produces from bacteria to identify novel antivirals, 3) examining methods to administer these molecules to mosquitoes, if the molecules have anti-viral activity in vivo, are molecules transferred by touch or how they can be altered to enhance contact efficacy, and 4) how the behaviour of mosquitoes can be exploit to deliver these antivirals. This research will lay the foundations for developing novel antiviral molecules from surfaces which mosquitoes are attracted to inhibit virus transmission in Aedes aegypti mosquitoes. 

Where does the project lie on the Translational Pathway?

T1 – Basic Research

Expected Outputs
  • The project will determine which antiviral can be delivered to mosquitoes by touch and provide and understanding on how these can influence virus development in the mosquito. Combined with the vector behaviour aspects, we will have all the elements required for a AVATSA’.
  • 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, PMcC, MM, and AK 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. Recent collaborative work between GLH and PMcC resulted in review in the prestigious Microbiome Journal, while GLH and AK have several collaborative projects planned.

Training Opportunities
  • Courses using R to examining big data sets.
  • Vector biology and training to work with high containment pathogens.
  • Workshops on machine learning and artificial intelligence.
  • Point pattern and spatiotemporal analyses.

Skills Required
  • A general understanding of vector biology, virology, and behaviour, as well as interest in statistics and coding.

Key Publications associated with this project

Murray GPD, Lissenden N, Jones J,  V Voloshin, KH Toé, E Sherrard-Smith, GM Foster, TS Churcher, JEA Parker, CE Towers, WM Guelbeogo, Sagnon N’Falé, H. Ranson, D. Towers, P. J. McCall (2020) Barrier bednets target malaria vectors and expand the range of usable insecticides. Nature Microbiol.5(1):40-47. https://rdcu.be/bZ6ip

Parker JEA, Angarita-Jaimes N, Abe M, Towers CE, Towers, D & McCall, PJ. (2015) Infrared video tracking of Anopheles gambiae at insecticide-treated bed nets reveals rapid decisive impact after brief localised net contact. Scientific Reports, 5, 13392.  https://doi.org/10.1038/srep13392 

Lynd A &McCall PJ. (2013) Clustering of host-seeking activity of Anopheles gambiae mosquitoes at the top surface of a human-baited bednet. Malaria J, 12, 267. https://doi.org/10.1186/1475-2875-12-267

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.

Saldaña MA*, Etebari K, Hart CE*, Widen SG, Wood TG, Thangamani S, Asgari S, Hughes GL. (2017) Zika virus alters the microRNA expression profile and elicits an RNAi response in Aedes aegypti mosquitoes.PLoS Neglected Tropical Disease 11(7):e0005760.