The genetic basis of host control of the microbiome in mosquitoes.

The microbiota of mosquitoes profoundly influences many phenotypes of the vector, including the ability to transmit pathogens to humans. As such, several microbe-based approaches are being investigated to reduce mosquito-borne disease. However, before such strategies can be implemented, it is essential to gain a greater understanding of how mosquitoes acquire and maintain their microbiota. From our limited understanding it appears mosquitoes acquire their microbiota in their aquatic and adult life stages, and environmental, genetic, and stochastic factors as well as microbial interactions shape the microbiome composition and abundance. Transmission of microbes between mosquitoes occurs by horizontal and/or vertical routes within and between species. As such the microbiome can be highly variable, and this variability could provide a possible explanation for differences in several host traits, including vector competence. When reared in a lab environment, mosquito lines usually have a similar microbiome, however we have found several diverse Aedes aegypti lines that have divergent microbiomes, indicating that non-environmental factors mediate these differences. This project will examine the role of host genetics in microbiome assembly in these diverse Ae. aegypti lines by exploiting microbiome transplantation approaches recently developed in the lab, as well as transcriptomics, genomics and CRISPR-Cas9 gene editing to garner a greater understanding of host genetic control of the microbiome in Ae. aegypti.

Where does the project lie on the Translational Pathway?

T1 – Basic Research

Expected Outputs

A greater understanding of how host genetics influences the microbiome of mosquitoes.

Training Opportunities

The student will have the opportunity to attend bioinformatics and biostatistics courses on microbiome or transcriptomic data processing and analysis, including the BIOL445 Bioinformatics and CHIC581 Statistical Genetics and Genomics modules at Lancaster University. The student also will have the opportunity to attend the Host-Microbe Symbioses: From genetics to metabolic interactions in Portugal.

Skills Required

Understanding of microbiology and vector biology. Experience of microbiome research and dynamical modelling (e.g. Lancaster’s Infectious Disease Modelling module) would be an advantage.

Key Publications associated with this project

Chaverra-Rodriguez D*, Macias VM, Hughes GL, Pujhari S, Suzuki Y, Peterson DR*, Kim D, Rasgon JL (2018) Targeted delivery of CRISPR-associated endonuclease (Cas9) into arthropod ovaries for heritable germline gene editing. Nature Communications. 9(1): 3008. Equal contribution.

Hegde S, NilyanimitP, Kozlova E,NAnderson EA, Narra HP, Sahni SK, Heinz E, Hughes GL. (2019) CRISPR/Cas9-mediated gene deletion of the ompA gene in an Cedecea neteri gut symbiont impairs biofilm formation and reduces gut colonization of Aedes aegypti mosquitoes. PLoS NTD. Accepted

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.

Hegde S*, Khanipov K, Albayrak L, Pimenova M, Saldaña MA*, Rojas MA, Hornett EA, Motl CM, Fredregill CL, Dennett JA, Debboun M, Fofanov Y, Hughes GL (2018) Microbial co-occurrence networks and microbiome community structure from lab-reared and field-collected mosquito vectors Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus. Frontiers in Microbiology. 9:2160

Macias VM, McKeand S, Chaverra-Rodriguez D, Hughes GL, Fazekas A, Pujhari S, Jasinskiene N, James AA, Rasgon JL (2019) Cas9-mediated gene in the malaria mosquito Anopheles stephensi by ReMOT Control. BioRxiv. https://doi.org/10.1101/775312

LSTM Themes and Topics – Key Words

Neglected tropical disease, Malaria and other vector borne disease

The call for applications for the 2020-21 round of studentships is now OPEN. Deadline for receipt of complete application 23:59 13th February 2020

Further information on the programme and application process can be found here