Vector-borne diseases cause over one million deaths annually in people worldwide. The long term objective of this research is to develop strains of vector mosquitoes that are genetically refractory to the transmission of pathogens such as those that cause malaria and dengue fever. These insects will be used to test the hypothesis that an increase in the frequency of a gene or allele that confers decreased vector competence to a population of mosquitoes will lead to a reduction in the incidence and prevalence of that disease. Following the successful efforts of our laboratory and others demonstrating the possibilities for engineering synthetic effector genes that produce pathogen refractory phenotypes in mosquitoes, we now propose to investigate specific drive mechanisms that would facilitate the safe and efficient spread of such genes in vector mosquito populations.
The SPECIFIC AIMS of this application have been designed to take advantage of the progress made with mosquito transgenesis and the fundamental nature of embryonic development in insects, to meet the need to research gene drive mechanisms.
The SPECIFIC AIMS are to: 1) Identify the cis-acting DNA and promoter elements responsible for the specific expression patterns of the nanos (nos) orthologous genes in Anopheles gambiae, An. stephensi and Aedes aegypti; 2) Construct and test synthetic transposable elements composed of mosquito nos genes and the Mos1 and piggyBac transposons; and 3) Determine if synthetic transposons can spread in caged populations of An. gambiae and Ae. aegypti.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG1-SSS-Q (10))
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Costero, Adriana
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University of California Irvine
Schools of Arts and Sciences
United States
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Juhn, J; Marinotti, O; Calvo, E et al. (2008) Gene structure and expression of nanos (nos) and oskar (osk) orthologues of the vector mosquito, Culex quinquefasciatus. Insect Mol Biol 17:545-52
Terenius, Olle; Marinotti, Osvaldo; Sieglaff, Douglas et al. (2008) Molecular genetic manipulation of vector mosquitoes. Cell Host Microbe 4:417-23
Adelman, Zach N; Jasinskiene, Nijole; Onal, Sedef et al. (2007) nanos gene control DNA mediates developmentally regulated transposition in the yellow fever mosquito Aedes aegypti. Proc Natl Acad Sci U S A 104:9970-5
Juhn, J; James, A A (2006) oskar gene expression in the vector mosquitoes, Anopheles gambiae and Aedes aegypti. Insect Mol Biol 15:363-72
Calvo, Eric; Walter, Marika; Adelman, Zachary N et al. (2005) Nanos (nos) genes of the vector mosquitoes, Anopheles gambiae, Anopheles stephensi and Aedes aegypti. Insect Biochem Mol Biol 35:789-98
Adelman, Zach N; Jasinskiene, Nijole; Vally, K J M et al. (2004) Formation and loss of large, unstable tandem arrays of the piggyBac transposable element in the yellow fever mosquito, Aedes aegypti. Transgenic Res 13:411-25
Jasinskiene, Nijole; Coates, Craig J; Ashikyan, Aurora et al. (2003) High efficiency, site-specific excision of a marker gene by the phage P1 cre-loxP system in the yellow fever mosquito, Aedes aegypti. Nucleic Acids Res 31:e147
James, A A (2002) Engineering mosquito resistance to malaria parasites: the avian malaria model. Insect Biochem Mol Biol 32:1317-23
Atkinson, Peter W; James, Anthony A (2002) Germline transformants spreading out to many insect species. Adv Genet 47:49-86
Coates, C J; Jasinskiene, N; Morgan, D et al. (2000) Purified mariner (Mos1) transposase catalyzes the integration of marked elements into the germ-line of the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 30:1003-8

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