Department Seminar Series - Dr. Corine Jackman Burden
Dr. Corine Jackman Burden
Mini-bioreactors to elucidate cell-cell communication in the human vaginal microbiome and the upper respiratory tract.
ABSTRACT:
Microbial interactions have a vital role in human health and disease. In the vagina, lactobacillus bacteria inhibit strict anaerobes while microbial imbalances may result in recurrent bacterial vaginosis. In the nasopharynx, the human pathogen Streptococcus pneumoniae (Spn) asymptomatically colonizes as a commensal, yet disseminates to the blood, brain, ear, and lungs to cause disease. Although infection is often detected at the macroscale, bacteria first colonize and interact with members of their community at high local densities at the microscale before the infection progresses to a detectable level. To investigate how bacteria interact at the microscale I adapted and implemented a microfluidic platform that enables high-parallel cultivation of bacteria to dissect and characterize microbial interactions. Cultivation takes place in aqueous droplets suspended in oil emulsion, creating thousands of monodisperse mini-bioreactors. My dissertation evaluated and validated microdroplets as an effective tool for recapitulating interactions between two common vaginal bacteria and developed a novel ex-vivo model system to culture the common and fastidious vaginal bacterium, Lactobacillus iners, in droplets containing vaginal fluid. My postdoctoral work focuses on developing a microfluidic device that keeps droplets static to investigate single-cell dynamics of a cell-signaling virulence determinant in Streptococcus pneumoniae. This technology enables measurement of cell density and assessment of the effect of environmental cues on signaling at the single-cell and population levels, as well as the role of heterogeneity as it emerges within and across populations. This microfluidic platform provides detailed single cell, pairwise interaction, and micropopulation-level insight that is not attainable using conventional techniques. The work will inform how cell-cell communication contributes to disease, and will help develop new diagnostics and therapeutics.