CAREER: Defining bacterial extracellular vesicle biogenesis and interactions within the host environment

About This Grant

Human microbiomes contain a mixed population of bacteria. These bacteria communicate with each other and with the host. Bacteria produce enclosed capsules, called vesicles, that shuttle information (DNA, protein, RNA) between cells and between the bacteria and the host. The communication can affect the types and relative numbers of bacteria present. They can affect the health of the host by stimulating or suppressing immune responses. They impact the local environment, which can also impact reproductive disease resistance, for example. This project is designed to understand bacterial signal production and transmission in a vaginal microbiome. How bacterial vesicles are produced will be investigated. How these capsules move through barriers such as mucus will be evaluated. How they affect the bacterial community composition, and ultimately, health, is of critical importance and will be studied. The project will also provide research experiences for local high school students and undergraduates. This project is designed to advance understanding of how microbiomes contribute to health, with a specific focus on bacterial extracellular vesicles (bEVs). bEVs are a poorly understood mode of cross-kingdom cellular communication. As membrane-bound, nano-sized particles that transport proteins, small molecules, and nucleic acids, bEVs facilitate cellular communication both locally and at distant sites throughout a host. The model system to be studied is the vaginal microbiome. This project has three technical objectives. The first is to characterize bEV biogenesis. The second is to evaluate how the mucus barrier impacts the fate of bEVs. The third is to determine how bEV function is affected in physiologically relevant environments. The proposed research will advance fundamental understanding of bEV loading and perturbations to bEV-based signaling in response to changes in the host environment. This work differs from current efforts as it examines bEV biogenesis, fate, and function in physiologically relevant model systems, allowing for a comprehensive understanding of the role of bEVs in microbe-host communication. Microcalorimetry, transcriptomics, lipidomics, and proteomics will be used to map changes to bEV loading and production in response to environmental perturbations. Multi-particle tracking technology will quantify the transport of bEVs across mucus barriers. Finally, mucus-based models will probe microbe-host interactions in physiologically relevant systems. Knowledge gained from this research will generate new insights and provide a deeper understanding of bEVs that will prove useful for engineers, microbiologists, and health researchers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.