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Gene drive in Drosophila melanogaster and Aedes aegypti

Navarro Paya, David 2017. Gene drive in Drosophila melanogaster and Aedes aegypti. PhD Thesis, Cardiff University.
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The yellow fever mosquito Aedes aegypti is the main vector for several important arboviral diseases such as dengue, yellow fever, chikungunya and zika. With the advent of genetic control strategies, new species-specific tools have emerged for the control of Aedes aegypti. This thesis describes attempts at building different gene drive systems aiming for both population suppression or population replacement, as well as exploring the possibility of inserting exogenous sequences in the male locus of Aedes aegypti. An underdominance system, consisting of two mutually rescuing killers, was investigated in Drosophila melanogaster. It did not work as expected in the configuration tested. The chosen NIPP1 killer gene could not be upregulated by tTAV when under the control of hsp83, UAS and tetO. tetO and tTAV2 resulted in a lethal positive-feedback loop. Gal4Groucho and LexAGroucho fusion proteins, previously used as corepressors in the literature, were lethal when under the control of the tetO-tTAV system. Males showed the expected feminisation phenotypes, invovling male palp shortening and less feathery antennae, upon Nix knock-out using CRISPR-Cas9. However, subsequent homology directed repair into the Nix gene in the male locus of Aedes aegypti did not succeed even after reiterated injections. Setting out from the hypothesis of Act4 haploinsufficiency in Aedes aegypti, the building of two different gene drive systems was attempted; female-specific underdominance and RIDL with drive. A CRISPR-Cas9 driven act4 knock-in unexpectedly confirmed act4 haplosufficiency in Aedes aegypti. Whilst the initially devised gene drive systems could not function as such, act4 haplosufficiency marked the finding of a new female-specific recessive flightless target (effectively sterile) for use in future population suppression drive systems.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords: Gene drive, Act4, Underdominance, Aedes aegypti, Drosophila melanogaster, Daisy-chain drive, synthetic biology, Genetic control of insects
Funders: MRC Case Studentship
Date of First Compliant Deposit: 9 May 2018
Last Modified: 17 Oct 2019 02:35

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