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Taking
aim at mosquitoes, Vector biologists at the School of Public Health are developing new approaches to disease control by studying the interaction between arthropod vectors and the disease pathogens that live within them. This work is vital, says Assistant Professor Liangbiao Zheng, Ph.D., because “many vector-borne diseases are coming back with a vengeance in parts of the world.” Diseases are not only re-emerging but spreading to new places, as with the West Nile virus discovered in New York City last summer. Associate Professor Serap Aksoy, Ph.D., specializes in research on the tsetse fly, which carries the protozoan that causes trypanosomiasis, also known as African sleeping sickness. Largely under control in the 1960s, trypanosomiasis is resurgent in central and East Africa, resulting in the worst epidemic of the century, according to Aksoy. Infection is fatal to farm animals; in humans, it causes intermittent comas and kills its victims if left untreated. Aksoy is investigating how a naturally occurring bacterium that lives in the tsetse fly can be altered genetically to make the fly inhospitable to the protozoan that causes sleeping sickness. She and her lab team have managed to introduce genes into the symbiotic bacteria and to place the bacteria into the flies. They are still working on finding genes whose expression will block the parasite. Aksoy hopes that eventually “engineered” flies that resist the protozoan causing sleeping sickness can replace natural populations in the field, thus stemming the spread of illness. Associate Professor Scott L. O’Neill, Ph.D., head of the vector biology section, is hoping to interfere with disease transmission by using a bacterial parasite found naturally in about one out of five insect species. The parasite, called Wolbachia, is able to actively invade field insect populations by manipulating the insects’ reproduction so as to favor its own vertical transmission. This ability, together with Wolbachia’s widespread distribution and ability to be introduced into new species in the laboratory, make it a very attractive tool to manipulate the genetics of a wide spectrum of insect-disease vectors. O’Neill is proposing to use Wolbachia in two different ways. The first is to harness Wolbachia as a vehicle to express foreign genes within mosquitoes. These genes could then be introduced into populations of mosquitoes, using Wolbachia’s natural spreading ability. The genes of interest to be expressed by Wolbachia would be those that could prevent human pathogens from being successfully transmitted by the vector—for example, single-chain antibodies that target the malaria parasite within the mosquito and prevent it from invading the insect’s salivary glands. Another, simpler strategy is to utilize virulent strains of Wolbachia to shorten the insect’s adult life. This approach exploits the fact that pathogens typically need a lengthy period to develop in the body of the insect before they can be transmitted to another human. (In any given mosquito population, only a small fraction, the oldest insects, is responsible for the majority of disease transmission. Since these older insects contribute little to reproduction, the mosquito population remains intact, but the pathogen is eliminated.) The O’Neill lab is currently evaluating the age-shortening strategy in tsetse flies and Aedes mosquitoes that transmit the dengue virus. They hope to extend this work to malaria vectors in the near future. Some Anopheles mosquitoes naturally resist the malaria protozoan. Zheng is exploring the genetic and molecular basis for the immune response that allows some mosquitoes to avoid infection. His group is zeroing in on the locus for the gene that determines susceptibility. Could Anopheles mosquitoes be bred with immunity to the malaria protozoan? Associate Professor Durland Fish, Ph.D., in addition to his work on West Nile, has spent the past decade staking out the territory of the tiny deer tick that carries Lyme disease. Among the tools at his disposal is remote sensing data provided by NASA, allowing Fish to use satellite images and other records to predict where the risk of tick-borne disease will be highest. This information is useful in planning prevention strategies, including use of the Yale-developed Lyme disease vaccine that became available last year. Research Scientist Leonard E. Munstermann, Ph.D., is doing basic research on sand flies, the vector for protozoa causing the two forms of leishmaniasis. One form causes disfiguring sores on the skin; the other leads to fatal disruptions of liver and spleen function. Leishmaniasis causes between 1.5 million and 2 million new illnesses annually, according to the World Health Organization. The fatal form is epidemic in eastern Brazil. (Ironically, when insecticide programs against malaria mosquitoes are terminated, it is the sand fly population that can surge to produce the prevalent disease problem.) A population geneticist, Munstermann is interested in whether genetically distinct sand fly populations should be reclassified as subspecies, some of which carry the protozoan, some of which don’t. This would have implications for vector control; there is no need to kill subspecies that don’t carry disease. He turned an informal population study of his own into an exhibit at Yale’s Peabody Museum. There he has displayed over 200 insects, from mayflies to butterflies, trapped in his suburban back yard. Munstermann is inspired not only by the possibility that he could help find a way to control the spread of leishmaniasis, but also by what the flies can tell us about all living organisms. “I’m interested in how things work. Here are flies no one has ever looked at. They’re important to humans. What are they made of?” He is drawn
to his work in part because understanding how genes interact
in tiny parasites and insects can provide information about human
beings as well. As he says: “DNA is DNA. We’re just
a more complex glop of DNA attempting to understand how less
complex glops of DNA interact.”
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