James, Anthony A. - University of California, Irvine - Department of Molecular Biology and Biochemistry

研究领域

Mosquitoes are arguably the most dangerous animals in the world. Annual human mortality from malaria transmitted by just one species, Anopheles gambiae, exceeds two million, while Aedes aegypti transmits viral diseases such as dengue and yellow fever. While these diseases occur principally in tropical zones, emerging pathogens such as Chikungunya and West Nile viruses may represent future medical and public health threats in more temperate regions. The goal of our laboratory is to develop novel, genetics-based control methods for blocking transmission of human pathogens by mosquitoes. The hypothesis driving our efforts is that the introduction into a population of mosquitoes of a gene that confers resistance to a pathogen should lead to a decrease in transmission of that pathogen. Implicit in this hypothesis is the assumption that less transmission will result in less disease and death. To test this hypothesis, a gene or allele that interferes with pathogen development or propagation must be discovered or developed, and subsequently spread through a mosquito population. Following implementation of this strategy, there should be measurable decreases in incidence and prevalence of the targeted disease. Research in three areas needs to be done to test the hypothesis. First, we must develop mosquitoes that are resistant to pathogens. Second, we must develop procedures for moving genes developed in the laboratory into wild mosquito populations. Finally, we must have sufficient information about the target mosquito population so that we can model and predict how the gene will behave in the population. This is important for both the introduction of the gene and establishing parameters by which the success of the introduction will be measured.

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Gantz, V. M., Jasinskiene, N., Tatarenkova, O., Fazekas, A., Macias, V. M., Bier, E. and James, A. A. (2015) Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito, Anopheles stephensi. Proc.Natl. Acad. Sci. USA 112(49):E6736-43: PMID:26598698. Chen, X.G., Jiang, X., Gu, J., Xu, M., Wu, Y., Deng, Y., Zhang, C., Bonizzon,i M., Dermauw, W., Vontas, J., Armbruster, P., Huang, X., Yang, Y., Zhang, H., He, W., Peng, H., Liu, Y., Wu, K., Chen, J., Lirakis, M., Topalis, P., Van Leeuwen, T., Hal,l A.B., Jiang, X., Thorpe, C., Mueller, R.L., Sun, C., Waterhouse, R.M., Yan, G., Tu, Z.J., Fang, X. and James AA. (2015) Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution. Proc Natl Acad Sci U S A. 112(44):E5907-15. PMID:26483478 Brown, D.M., Alphey, L.S., McKemey, A., Beech, C., and James, A.A. (2014) Criteria for identifying and evaluating candidate sites for open-field trials of genetically-engineered mosquitoes. Vector Borne Zoo. Dis., 14, 291-299. PMID: 24689963 Franz, A.W.E., Sanchez-Vargas, I., Raban, R.R., Black, W.C., James, A.A. and Olson, K.E. (2014) Fitness impact and stability of a transgene conferring resistance to dengue-2 virus following introgression into a genetically-diverse Aedes aegypti strain. PLoS NTD 8 (5): e2833. PMID: 24810399 Chagas, A.C., Ramirez, J.L., Jasinskiene, N., James, A.A. Ribeiro, J.M.C., Marinotti, O. and Calvo, E. (2014) The collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti. Proc. Natl. Acad. Sci. USA 111 6946-6951. PMID: 24778255 Marinotti, O., Ngo, T., Burini-Kojin, B., Chou, S., Nguyen, B., Juhn, J., Carballar-Lejarazú, Marinotti, P., Jiang, X, Walter, M., Tu, Z., Gershon, P.D. and James, A.A. (2014) Integrated proteomic and transcriptomic analysis of the Aedes aegypti eggshell. BMC Developmental Biology 14 (1) 15. PMID: 24707823 Ramsey, J.M., Bond, J.G., Macotela, M.E., Facchinelli, L., Valerio, L. Brown, D.M., Scott, T.W. and James, A.A. (2014) A regulatory structure for working with genetically-modified mosquitoes: Lessons from Mexico. PLoS Negl Trop Dis 8(3): e2623. doi:10.1371/journal.pntd.0002623