Monday, September 26, 2016
On September 26, 2016, Rachel Brouillette successfully defended her thesis titled, "Arenaviruses:glycoproteins, antibodies, and cell entry". She is pictured with her mentor Dr. Wendy Maury.
The family Arenaviridae consists of over 30 members, some of which can infect humans and cause severe hemorrhagic fever. Three arenaviruses: Machupo virus (MACV), Junín virus (JUNV), and Lassa virus (LASV), are causative agents of Bolivian hemorrhagic fever, Argentine hemorrhagic fever, and Lassa fever, respectively. Epidemics of these diseases can carry high rates of morbidity and mortality, and due to a lack of available countermeasures, all three viruses are considered category A priority pathogens by the CDC. For MACV and JUNV, neutralizing antibodies are important for viral clearance and can be used therapeutically, however, antibodies that can neutralize both viruses are uncommon. Because neutralizing antibodies exclusively target arenavirus glycoprotein complexes (GPCs), my research largely focused on identifying antibody targets and structural impediments to cross-species neutralizing antibodies between MACV and JUNV GPCs. This work included assessing the role of N-linked glycans on the GPCs that occlude protein surfaces.
Aside from that work, I also developed a project related to the central interest of my lab, which is phosphatidylserine-dependent entry of enveloped viruses. Usually, LASV binds to the cell surface receptor, α-dystroglycan (αDG). While αDG is ubiquitously expressed, multiple studies have suggested that alternative receptors exist on cell types that express LASV-incompatible forms of αDG. My work with LASV demonstrates that phosphatidylserine receptor, TIM-1, can function as a receptor for LASV entry in such cells, and mediates virion internalization in a phosphatidylserine-dependent manner.
About Rachel
My long journey to the University of Iowa began as an undergraduate at Iowa State University. There, I majored in Biology and minored in Microbiology, Entomology, and Emerging Global Diseases. My first exposure to research was a summer internship after my sophomore year at the University of Nebraska Eppley Research Institute. I worked in a yeast genetics lab studying the molecular mechanism behind the genetic disorder, Huntington’s Disease. Having enjoyed lab work, I later began working as an undergraduate research assistant at the USDA back in Ames, where I worked surveillance of Campylobacter and Salmonella contamination in meat production throughout Iowa, especially in turkeys.
After graduation and an additional semester of full-time employment at the USDA, I moved to Athens, Georgia to pursue an M.S. in Entomology from the University of Georgia. There I spent a lot of time learning all there is to know about insects, including a particularly memorable three-day tenure at Mosquito Camp. My research, though, focused on polydnaviruses, which are viruses maintained in wasp ovaries and injected with an egg to parasitize caterpillars. My work characterized an array of polydnavirus-induced metabolic disorders that prevent the caterpillar from metamorphosis.
After graduation, I moved to Iowa City to join the MPH program in Epidemiology. I lasted one week before I realized it was not for me, so I spent the remainder of the year as a genomics technician in the Department of Biology. There I used genomic hybridization microarrays to hunt for underlying genes involved in the development of cleft lip/palate. Finally, in the fall of 2012, I joined the Ph.D. program in the Department of Microbiology where I have spent the last few years working in Dr. Wendy Maury’s lab studying various aspects of hemorrhagic-fever causing viruses.