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Anthony A. James

Distinguished Professor, Microbiology & Molecular Genetics School of Medicine Distinguished Professor, Molecular Biology and Biochemistry School of Biological Sciences

PH.D., University of California, Irvine

Research Interests Molecular biology of insect vectors of disease, genetics of vector competence, malaria, dengue fever.

Faculty/lab web: http://www.ucihs.uci.edu/microbio/

Faculty/lab web: http://mbb.bio.uci.edu/home.html

Faculty/lab web: http://stopdengue.hs.uci.edu/

Graduate Programs: Immunology and Pathogenesis Biotechnology

Professional Society American Society of Tropical Medicine and Hygiene American Association for the Advancement of Science American Committee on Vector Entomology Royal Entomological Society Entomological Society of America Genetics Society of America Society of Vector Ecology

Abstract 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 the West Nile virus 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. In parallel lines of research, we are evaluating the genetic control hypothesis using mosquitoes that have been engineered to be resistant to the pathogens that cause malaria or dengue fever. Our research group has focused first on the laboratory component of this strategy and we identified three research goals that must be met in order to make pathogen-resistant mosquitoes. The first goal was to identify as a target of intervention a tissue in which specific interactions occur between the pathogens and host mosquitoes. Our approach has been to isolate and characterize genes expressed specifically in that tissue, and use the control DNA sequences of these genes to express a coding region that will confer resistance to the pathogens. Our second goal was to develop transgenesis technology that would allow the introduction into the genome of mosquitoes a gene or genes capable of interfering with pathogen development. Our final goal was to develop a hybrid gene that interferes with pathogen development when expressed in the mosquito. This will be the gene that is spread through a target population and is expected to affect pathogen transmission. Our laboratory has had much success with these goals using avian malaria as a model. We are working now with the most lethal human malaria parasite, Plasmodium falciparum. Most recently, we have partnered with a network of laboratory and field scientists and modellers to develop genetic control approaches for preventing the transmission of dengue viruses. Recently we have started experiments that will investigate the second major research area, the movement of laboratory-developed, pathogen-resistance genes into wild populations of mosquitoes. We have planned a number of experiments that will test the mobility of genes in caged populations of mosquitoes. These experiments should give us an indication of what will be needed to drive introduced genes in a safe and effective manner through target populations. This work is being explored firts with the vectors of dengue viruses. The laboratory also has researched malaria parasite development in the mosquito. Our efforts have identified genes whose products may be therapeutic or vaccine targets. For a more detailed description of our research efforts, please see the website: http://darwin.bio.uci.edu/~faculty/james/main.html

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Updated: Last Updated: 03/04/2009