Speaker
Description
Chemical interactions enable bacteria to associate closely with organisms across all domains of life. Beyond mutualistic and pathogenic interactions, small molecules known as metabolites not only provide essential building blocks for cellular membranes but also facilitate interactions between microbes and their hosts. A major challenge in studying metabolites involved in host-microbe interactions is determining whether a given metabolite corresponds to the site of colonization. Mass spectrometry imaging (MSI) offers a powerful approach for unraveling the metabolic fingerprints and interactions of microbes within animal tissues.
To study the endosymbionts of chemosynthetic mussels of the genus Bathymodiolus from deep-sea vents, I integrated high-resolution MSI with fluorescence labeling of the intracellular symbionts. With this correlative approach, I was able to assign hundreds of metabolite distributions to either the host or its symbionts within a single measurement, revealing the heterogeneous metabolic landscape of the animals’ symbiotic organ on a micrometer scale.
To investigate the site-specific metabolism of another intimate microbe that colonizes specific micro-niches in its host, I applied my approach to study the interaction between the pathogen Helicobacter pylori and stomach epithelium. H. pylori colonizes the human stomach and can persist for decades. Since MSI is limited to metabolic snapshots, the next frontier in studying spatial metabolism involves mimicking and experimentally perturbing the tissue microenvironments that arise from host-microbe interactions. I use a novel gastric organoid model to monitor and manipulate the cell-cell interactions between bacteria and host, ultimately resolving micrometer-scale metabolic interactions between clonal microcolonies and the gastric epithelium through MSI.
By pivoting between research on environmental symbioses and pathogenesis, my goal is not only to discover but also to test the factors that drive the metabolic heterogeneity underlying host-microbe interactions.
