Identifying resistance liabilities to new insecticides in mosquitoes that transmit urban tropical diseases

Increasing urbanisation in tropical disease endemic countries is elevating the threats posed by urban-adapted mosquito vectors of tropical diseases. Of particular concern in Africa are Aedes aegypti, which transmits dengue, yellow fever and Zika viruses, and the recently invasive Anopheles stephensi, vector of both Plasmodium falciparum and Plasmodium vivax malaria. Both thrive in urban environments where traditional mosquito control methods such as indoor residual spraying are challenged by poor community acceptance.  New ways to prevent mosquito-borne disease transmission and control outbreaks in urban environments are urgently required. Volatile insecticides developed for agriculture may be exploited in new products targeting urban mosquitoes to reduce the spread of disease and there is high promise for combination with new insecticides, such as the butanolide class, which show a different mode of action which might be expected to limit resistance. However, mosquitoes are genetically diverse and well-primed to develop rapid resistance to insecticides. Research to date on this new insecticide class has focused on agricultural pests, and despite high potential for use within mosquito-borne disease control tools, studies to date on whether mosquitoes have capacity to resist toxicity to these new insecticides are lacking.

This PhD project will investigate the resistance capabilities of key urban mosquito vectors to aid the development of a new generation of mosquito control products. This will involve a combination of molecular biochemical laboratory experiments, mosquito line selection experiments with associated transcriptomic analysis, and in silico biochemical and genomic investigations using data from the Anopheles and Aedes aegypti 1000 genomes projects, along with novel Anopheles stephensi data generated by a Wellcome Trust funded LSTM programme.

Where does the project lie on the Translational Pathway?

T1 – Basic Research, T3 – Evidence into Practice

Expected Outputs

This PhD project will use varied biochemical approaches, coupled with selection experiments, transcriptomic analyses and genomic analyses from extant data to generate knowledge and tools to guide deployment of this new insecticide and co-formulations. We anticipate that the variety of approaches will generate cross-cutting publications and reports for industry, control programmes and their funders to generate follow on larger-scale field evaluation work.

Training Opportunities

In addition to training at LSTM, training will be provided via placements with Bayer crop science under the supervision of  Uwe Plushkell  and Ralf Nauen . Additional training opportunities with IVCC may be explored

Skills Required

Laboratory skills in molecular biology/ biochemistry

Interest in evolutionary and molecular genetics

Strong interest in vector biology and control

Key Publications associated with this project

Hayward A, et al. (2019) The leafcutter bee, Megachile rotundata, is more sensitive to N-cyanoamidine neonicotinoid and butenolide insecticides than other managed bees. Nature Ecol Evol 3:1521-4

Yunta CH, et al. (2019) Cross-resistance profiles of malaria mosquito P450s associated with pyrethroid resistance against WHO insecticides.  Pest. Biochem. Physiol. 161:61-67

Moyes CL, et al. (2021) Assessing cross‑resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations. Parasites & Vectors 14:11

Dusfour I, et al. (2019) Management of insecticide resistance in the major Aedes vectors of arboviruses: Advances and challenges. PLoS Negl Trop Dis 13: e0007615.

Oumbouke WA, et al. (2020) Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Côte d'Ivoire. Sci Rep. 10:15066

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