Cracking the Mosquito Genome

    By Mary L. Holden

    Picture a mosquito laboratory. The lucky ones who live there—in a secure, resort-like atmosphere known as an Arthropod Containment Level 2 insectary—dine on human blood (provided by the American Red Cross after the use-by date expires) through special containers that mimic skin. Larvae hatch in carefully tended tubs of water. The mosquito lab at the University of Arizona, led by Michael Riehle, Ph.D., keeps two special kinds of mosquitoes—some that carry the malaria parasite and others that have been genetically engineered to kill the malaria parasite in their bodies.

    Riehle and his collaborators at the University of California, Davis are credited with discovering that by “making a small change to the mosquito genome,” carriers of malaria known by their scientific name as Anopheles stephensi will eventually no longer be able to play a role as vectors. Riehle described his work in the lab: “We inject DNA into newly laid eggs to insert our gene and a fluorescent marker into the genome. We then rear these injected eggs to adulthood, let them mate and then look at their offspring (as late larvae or pupae) to see if they inherited our gene and fluorescent marker.

    DNA microarray technology has furthered the science of molecular biology upon which scientists like Riehle base this kind of research. He used the University of Arizona’s microarray machine, which has probes that correspond to the “approximately 15,000 protein-coding genes in the mosquito genome for testing mosquito gene samples,” to determine which of the probes would bind to the gene that prevents malaria from being carried, Riehle explained. Although this technology played a small role in the work on the malaria-resistant mosquito, it nevertheless helped further the research.

    Currently in Riehle’s lab, malaria-resistant mosquitoes are being mated with carrier mosquitoes. Half of the resulting progeny will not become vectors, and over enough generations, the ability to carry malaria in a mosquito’s body will breed out. While this is not the focus of Riehle’s research, he says that other labs around the world are trying to increase the heritability rate of malaria resistance from the usual 50 percent to as much as 90 percent to 100 percent.

    “This will allow the malaria resistance to spread through the wild population, but it can take years until it happens naturally because there will be many greenhouse trials and exhaustive testing by state and local governments and public health agencies before the non-carriers can be released,” Riehle noted. “For example, although these mosquitoes will not be able to transmit malaria, we want to make sure that they don’t begin transmitting other mosquito-borne diseases.”

    Once thorough testing has been completed, the ultimate goal is to totally replace the malaria-carriers with the malaria-killers in the wild, especially in sub-Saharan Africa. According to the World Health Organization’s Fact Sheet No. 94 (April 2010), “In 2008, there were 247 million cases of malaria and nearly one million deaths—mostly among children living in Africa … [where] a child dies every 45 seconds of malaria .…”

    This important discovery will take some time to make a positive change in the world. Riehle is looking for an answer as to why this gene modification kills the malaria parasite. “We have some ideas about what the specific killing mechanism is,” he said, “and we’re still testing.”



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