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  Investigating systems for reducing pathogen transmission by mosquitoes


   Biomedical and Life Sciences

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Prof S Sinkins  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

The project will use molecular biology techniques to study mosquitoes, with the aim of contributing to the development of novel biological and genetic strategies for controlling mosquito-borne pathogens such as malaria parasites and arboviruses. Based at Lancaster University, it will also involve a period of at least one year based at Oxitec Ltd., a leading biotechnology spin-off company based in Oxfordshire.

The Lancaster University laboratory will study Wolbachia inherited intracellular bacteria in mosquitoes. Wolbachia can spread through insect populations by manipulating their reproduction, using patterns of sterility known as cytoplasmic incompatibility. Previous studies in Aedes and Anopheles mosquitoes have demonstrated that certain strains of Wolbachia can inhibit or block the transmission of mosquito-borne pathogens, including arboviruses and Plasmodium. The project will investigate Wolbachia-mosquito interactions at a molecular level, including the priming of the host innate immune system that can occur in the presence of Wolbachia. It will utilize mosquito manipulation and injection techniques, cell lines, gene knockdown and gene expression studies.

At Oxitec the 'RIDL' system (Release of Insects carrying a Dominant Lethal gene) was developed and has already been shown to work successfully for population suppression in Aedes mosquitoes. The project will investigate potential population replacement methods, which could ultimately be used take pathogen-inhibiting transgenes to high population frequency or fixation in natural mosquito populations. Several approaches could be taken; one is the 'killer-rescue' pair, where 'sterile' males produce sex & stage-specific progeny inviability when they mate with wild-type females, while a separate line contains a sterility 'rescue' factor, thus giving them a selective advantage compared to wildtypes. The project will involve the creation and characterization of transgenic lines of mosquitoes.

Funding Notes

MRC Industrial CASE studentship
Eligibility requirements are listed at
http://www.mrc.ac.uk/Fundingopportunities/Applicanthandbook/Studentships/Eligibility/index.htm

References

Kambris Z, Cook PE, Phuc HK, Sinkins SP (2009) Immune activation by life-shortening Wolbachia and reduced filarial competence in mosquitoes. Science 326: 134-6.
Blagrove MS, Arias-Goeta C, Failloux A-B, Sinkins SP (2012) The Wolbachia strain wMel induces cytoplasmic incompatibility and blocks dengue transmission in Aedes albopictus. Proceedings of the National Academy of Sciences of the USA 109:255-60.
Thomas, D.D., Donnelly, C.A., Wood, R.J. and Alphey, L.S. (2000). Insect population control using a dominant, repressible, lethal genetic system. Science, 287: 2474-2476
Wise de Valdez, M.R., Nimmo, D., Betz, J., Gong, H., James, A.A., Alphey, L., and Black, W.C., IV (2011). Genetic elimination of dengue vector mosquitoes. Proceedings of the National Academy of Sciences (USA) 108:4772-4775