We are working on genetic approaches that target vector mosquitoes to control transmission of malaria parasites. We are testing the hypothesis that the introduction into a population of vector mosquitoes of a gene conferring resistance to malaria parasites will decrease pathogen transmission and result in less disease and mortality In humans. The goals that must be met to test this hypothesis Include the development of mosquitoes engineered genetically to be incapable of the transmission of malaria parasites. Major steps in the laboratory efforts to develop these insects Included the adaptation of transgenesis technologies for the stable introduction of genes into the appropriate vector mosquito species, the discovery of promoter sequences from mosquito genes that could be used to express effector molecules at a time and place In the insects so as to optimize the impact on the target pathogens, and the formulation of effector genes that efficiently prevent the development of pathogens while at the same time Impose negligible fitness loads on the mosquitoes carrying them.
The Specific Aims of this proposal address the working hypothesis that it should be possible to engineer the effector genes so as to achieve the target of zero parasite prevalence (percent of all mosquitoes with an infection) and mean intensities of infection (average number of parasites in only those mosquitoes infected) in the salivary glands of parasite-challenged mosquitoes.
The Specific Aims are 1) optimize expression of single-chain antibodies (scFv) that disable Plasmodium falciparum In the midgut and hemolymph of transgenic Anopheles stephensi;2) construct and test in parasite-challenge assays transgenic An. stephensi carrying single and multiple optimized scFvs for their ability to prevent parasites from infecting midguts and salivary glands;and 3) evaluate the fitness of strains of An. stephensi carrying one or more transgenes expressing anti-parasite scFvs relative to control laboratory colonies using life-table parameters. Gene cloning, transgenesis (both transposon- and site-specific recombination-mediated), fitness assays and parasite-challenge assays are used to develop and test genes that confer resistance In An. stephensi to the human malaria parasite, P. falciparum.

Public Health Relevance

Malaria eradication will require vector-control strategies that are both self-sustaining and not affected by migration of infected humans and mosquitoes. Replacement of wild malaria-susceptible mosquito populations with transgenic strains that block parasite development could Interrupt the cycle of disease transmission and support eradication efforts.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Costero, Adriana
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Irvine
Schools of Arts and Sciences
United States
Zip Code
Biedler, James K; Qi, Yumin; Pledger, David et al. (2015) Maternal germline-specific genes in the Asian malaria mosquito Anopheles stephensi: characterization and application for disease control. G3 (Bethesda) 5:157-66
Marinotti, Osvaldo; Ngo, Tuan; Kojin, Bianca B et al. (2014) Integrated proteomic and transcriptomic analysis of the Aedes aegypti eggshell. BMC Dev Biol 14:15
Costa-da-Silva, Andre L; Marinotti, Osvaldo; Ribeiro, Jose M C et al. (2014) Transcriptome sequencing and developmental regulation of gene expression in Anopheles aquasalis. PLoS Negl Trop Dis 8:e3005
Wang, Yueqiang; Tan, Anjiang; Xu, Jun et al. (2014) Site-specific, TALENs-mediated transformation of Bombyx mori. Insect Biochem Mol Biol 55C:26-30
Chagas, Andrezza Campos; Ramirez, José Luis; Jasinskiene, Nijole et al. (2014) Collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti. Proc Natl Acad Sci U S A 111:6946-51
Jiang, Xiaofang; Peery, Ashley; Hall, A Brantley et al. (2014) Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi. Genome Biol 15:459
Xu, J; Wang, Y; Li, Z et al. (2014) Transcription activator-like effector nuclease (TALEN)-mediated female-specific sterility in the silkworm, Bombyx mori. Insect Mol Biol 23:800-7
Macias, V; Coleman, J; Bonizzoni, M et al. (2014) piRNA pathway gene expression in the malaria vector mosquito Anopheles stephensi. Insect Mol Biol 23:579-86
Carballar-Lejarazu, Rebeca; Jasinskiene, Nijole; James, Anthony A (2013) Exogenous gypsy insulator sequences modulate transgene expression in the malaria vector mosquito, Anopheles stephensi. Proc Natl Acad Sci U S A 110:7176-81
Wang, Chunmei; Xu, Jiabao; Zhou, Xiaohong et al. (2013) Strongyloidiasis: an emerging infectious disease in China. Am J Trop Med Hyg 88:420-5

Showing the most recent 10 out of 23 publications