Matthew DeGennaro, Ph.D.
I am a neurogeneticist with 20 years of experience in biomedical research. Throughout my scientific career, I have used molecular genetics to address biological questions. My graduate training at NYU Medical Center was with Ruth Lehmann, one of the founders of developmental genetics, who has made fundamental contributions to the fields of germ cell and RNA biology. My postdoctoral training at Rockefeller University was with Leslie Vosshall, a leader in the field of olfaction who initially identified insect olfactory receptors and determined their unique mechanism of action. During my post-doc, I created the first mosquito mutant using zinc-finger nucleases to initiate the molecular genetic analysis of olfactory receptor function in Aedes aegypti. My work revealed new knowledge about the integration of host cues, mosquito host-preference, mosquito nectar-seeking, and the mechanism of DEET repellency. My current goal is to identify olfactory receptors that mosquitoes use to sense their human and plant hosts. These genes will provide molecular targets that can be used to screen for new chemicals to modify mosquito behavior. My results have appeared in a number of peer-review publications including Nature, Developmental Cell, Current Biology, PLOS Genetics, and the Journal of Biological Chemistry. My laboratory at Florida International University studies the molecular genetics of mosquito host detection.
Despite the danger that mosquito host-seeking behavior poses to human health, little progress has been made in understanding its genetic basis. Body odor and carbon dioxide are long-range, attractive cues that guide mosquitoes to their human hosts. Mosquitoes also depend on plant hosts for nutrients. Nectar is usually the first meal mosquitoes ingest. Since male mosquitoes do not blood feed, nectar is their principle energy source. Similar to human host attraction, plant volatiles such as floral odors guide mosquitoes to nectar sources. Understanding the odors that attract mosquitoes and the receptors required to sense these odors, will allow for new approaches to manipulate mosquito behavior.
To identify the mosquito receptors that respond to human odor and plant volatiles, I developed a technique for targeted mutagenesis in the dengue fever mosquito, Aedes aegypti, using zinc-finger nucleases. Using this approach, I demonstrated that orco, an olfactory co-receptor, enables host odor and nectar volatile attraction, the preference of mosquitoes for human hosts, and DEET-driven repellency. By establishing techniques for behavioral neurogenetics in the mosquito, my work has opened the door to the comprehensive genetic analysis of these important disease vectors.
Going forward, my research program is focused on the olfactory receptors that mediate the mosquito’s human and plant host-seeking behavior and the genes that regulate their appetitive drives. To do this, I am taking advantage of the highly stereotyped behavioral transitions that occur during the gonotrophic cycle. In particular, after a mosquito has taken a blood meal, she no longer seeks human hosts and begins to look for a place to lay eggs. I initiated the generation of a neurotranscriptome of chemosensory, neural, and reproductive tissues to document the changes in gene expression that underlie this behavioral switch. The candidate genes I am identifying using this approach will provide targets for a screen to identify novel regulators of mosquito behavior. By understanding the genetic basis of mosquito host-seeking, I will illuminate fundamental processes that drive innate behavior while identifying new molecular targets for mosquito control.
Header mosquito photo by Alex Wild.