Contextualizing host-microbe interactions using chemical cartography
Dr. Laura-Isobel McCall(University of Oklahoma)
– Date/time change
Title: Spatial context is essential in understanding host-microbe-environment interactions. The McCall laboratory leverages an approach called “chemical cartography” to study chemical communication in 3D. By combining 3-dimensional mapping, systematic sample collection and liquid chromatography-tandem mass spectrometry, we characterize the small molecule context surrounding invading pathogens, and then leverage this information to develop novel treatments for infectious diseases. Current research in the laboratory focuses on Trypanosoma cruzi protozoan parasites, the causative agents of Chagas disease. T. cruzi parasites have selective tissue tropism, preferentially causing cardiac damage, megacolon and megaoesophagus. Using chemical cartography, we determined that different regions of the heart display distinct overall molecular signatures and we showed regiospecific differences in small molecule patterns between fatal and non-fatal infections. Likewise, we assessed microbial and metabolic changes systematically throughout the gastrointestinal tract of T. cruzi-infected and control animals. This enabled us to build a three-dimensional model of functional microbiome disturbances, in correlation with localized parasite burden. The greatest microbial disruptions were observed in the colon, where parasite burden was the highest, and in the esophagus, in association with changes in the small molecule profile. Pharmacological modulation of some of these pathways significantly improved animal survival in acute-stage Chagas disease models. Overall, these results are expanding our understanding of the small molecule-mediated communication between host, parasite and microbiome and leading to new therapeutics for infectious diseases.
Bio: Dr. McCall’s work focuses on the interplay between mammalian hosts, their environment and microbes, with the ultimate goal of improving human health. Dr. McCall conducted undergraduate research on leishmaniasis with Drs. Martin Olivier and Greg Matlashewski at McGill University in Montreal, Canada, followed by a PhD on visceral leishmaniasis determinants under the direction of Dr. Matlashewski. She then joined the Center for Discovery and Innovation in Parasitic Diseases (CDIPD, first at UCSF and now at UCSD) as a postdoctoral fellow, working with Drs. James McKerrow on high-throughput, high-content anti-trypanosomal drug discovery. Her more recent work focuses on integrating mass spectrometry-based metabolomics with three-dimensional reconstructions to map the chemical communication between Trypanosoma cruzi and the host directly within infected organs. She joined the faculty at the University of Oklahoma in August 2017.
Dr. McCall is the guest of Dr. Dajana Vuckovic