Bioinformatic and molecular approaches toward molecular surveillance of insecticide resistance in African Aedes aegypti

The most important arboviruses affecting humans originated in Africa, yet research on the major Aedes vectors in Africa, where misdiagnosis and malaria-focus leads to underestimated arboviral impacts, lags far behind that elsewhere in the world. Indeed, current WHO dengue control guidelines are based on evidence from Latin America and South East Asia, and their applicability to African vector-disease settings is unclear. African Aedes aegypti are genetically distinct from those elsewhere in the world, and are more diverse phenotypically, suggesting control strategies may need adaptation. With increasing frequency and severity of outbreaks of dengue, chikungunya and an ever-present threat of yellow fever outbreaks, this knowledge gap is rapidly gaining in importance.

Insecticides play a crucial role in Aedes control and some diagnostic molecular markers for target site mutations are in use in control programmes in Latin America and SE Asia. This project will focus on the genetic basis of insecticide resistance in African Ae. aegypti, which is poorly understood, and the identification of markers for deployment in molecular surveillance of resistance. Of particular interest is how mechanisms may converge or vary geographically and link with hybridisation between the Aedes aegypti subspecies found in Africa. The project will build on recent and ongoing transcriptomic studies at LSTM and utilise data from the ongoing Aedes 1000 genomes project. Adapting successful methodologies from the highly-successful Anopheles gambiae 1000 genomes project, the project will use whole-genome sequence data to identify genomic areas under selection, coupled with transcriptomic analyses and in vitro functional validation of key genes and markers. The diagnostic capacity of resulting assays will be evaluated in phenotyped samples from wild African populations.

Where does the project lie on the Translational Pathway?

T1 – Basic Research, T2 – Human/Clinical Research, T3 – Evidence into Practice

Expected Outputs

The work is anticipated to produce a range of outputs from ‘omic’-level variant/gene discovery, links with hybridisation and validation to diagnostic development and testing. The Weetman and Paine groups have a strong track record in these areas with previous PhD students producing highly-cited outputs in journals such as Nature Communications and PLoS Genetics.  This is a highly novel area, which is likely to generate significant attention and impact via a well-established network of African collaborators.

Training Opportunities

Genomics and transcriptomics

Advanced statistics including machine learning

Biochemical in vitro analyses

Skills Required

Laboratory-based skills in molecular biology

Strong interest in/ knowledge of evolutionary, molecular and population genetics

Highly numerate with good general knowledge of statistical analysis 

Interest in vector biology and control

Key Publications associated with this project

Weetman, D, Kamgang B, Badolo A, Moyes CL, Shearer FM, Coulibaly M, Pinto J, Lambrechts L, McCall PJ (2018) Aedes mosquitoes and Aedes-borne arboviruses in Africa: current and future threats. International Journal of Environmental Research and Public Health 15: 2.

Badolo A, Sombié A, Pignatelli PM, Sanon A, Yaméogo F, Wangrawa DW, Sanon A, Kanuka H, McCall PJ, Weetman D (2019) Insecticide resistance levels and mechanisms in Aedes aegypti populations in and around Ouagadougou, Burkina Faso. PLoS Negl Trop Dis. 13:e0007439.

Lucas ER, Miles A, Harding NJ, Clarkson CS, Lawniczak MKN, Kwiatkowski DP, Weetman D, Donnelly MJ; Anopheles gambiae 1000 Genomes Consortium (2019) Whole-genome sequencing reveals high complexity of copy number variation at insecticide resistance loci in malaria mosquitoes. Genome Res. 29:1250-1261.

Moyes CL, Vontas J, Martins AJ, Ng LC, Koou SY, Dusfour I, Raghavendra K, Pinto J, Corbel V, David J-P, Weetman D (2017) Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans. PLoS Negl Trop Dis 11(7): e0005625

Clarkson CS*, Weetman D*, Essandoh J, Yawson AE, Maslen G, Manske M, Field SG, Webster M, Antão T, MacInnis B, Kwiatkowski D, Donnelly MJ (2014) Adaptive introgression eliminates a major genomic island of divergence but not reproductive isolation between Anopheles gambiae sibling species. Nature Communications 5:4248

LSTM Themes and Topics – Key Words

Malaria and other vector borne diseases; neglected tropical diseases; resistance research and management