Insect vector-borne diseases continue to burden a large fraction of the world's population. Understanding the basic biology of the insects responsible for transmitting the pathogens that cause these diseases has been and will continue to be essential for the development of effective strategies of control. Technological advances often provide novel opportunities to enlarge our understanding of basic biology. This project will result in the creation of a genetic resource consisting of transgenic lines of the human malaria mosquito Anopheles stephensi expressing the transcription factor Gal4 specifically in hemocytes. This collection of lines will serve as a valuable tool for the investigation of the cellular immune system in mosquitoes, which consists of hemocytes that are responsible for encapsulation and phagocytosis as well as synthesis of antimicrobial proteins. This aspect of the mosquito's immune system is less well understood than the more-well-studied humoral immune system although there has been growing realization that it is an important mediator of microbial infections in these insects. This collection of lines expressing Gal4 specifically in hemocytes will be used subsequently to label hemocytes in vivo to facilitate their visualization under a variety of physiological conditions, to manipulate hemocyte gene expression (silencing, overexpression, mis-expression) to assess the genetic basis of hemocyte growth, development and/or function and to express cell-death or cytotoxic genes to specifically ablate hemocytes or subpopulations of hemocytes to assess the impact on various physiological processes.
Most mosquito species do not and cannot transmit malaria because they are unsuitable hosts for malaria parasites. Mosquitoes that are good hosts for the parasites fail to eliminate the invading parasites using their potent innate immune systems. Understanding how the mosquito's immune system works will allow scientists to understand how certain mosquitoes have become hosts of the malaria parasite and provide researchers with new opportunities to develop methods to interfere with this host/pathogen relationship and reduce malaria transmission.