Northwestern University Feinberg School of Medicine

Mandel Laboratory

Research

Microbiome colonization

Animals are symbiotic superorganisms, composed of eukaryotic cells and specific microbial residents that perform essential functions for their host. In humans there is evidence that half of the cells in our body are microbial. Many of these organisms reside in human gut, skin, and oral cavity, where the presence of healthy communities is critical for proper development of the immune system, of the host tissue, and for nutrient acquisition.

Model systems are leading to illustrate the molecular mechanisms that allow for specific relationships to be recapitulated during each host generation. Our research uses the simplified symbiosis between the Hawaiian bobtail squid and its luminous light-organ bacterial symbiont, Vibrio fischeri, to ask two broad questions: (1) During each new host generation, how does molecular communication ensure that the host becomes colonized exclusively with the correct symbiont? and (2) How do microbe-host interactions evolve to lead to new associations or to maintain robust interactions when the underlying signaling changes?

Symbiotic development

There are three broad stages -- termed initiation, accomodation, and persistance -- during which specific bacterial behaviors are required for colonization. To identify the molecular bases underlying these important behaviors, we are applying a high-throughput genetic approach to identify and characterize novel colonization factors. We have identified over 200 such factors and are combining genetic and imaging approaches to characterize their role during symbiosis.

Evolution of microbe-host specificity

The squid hatch into seawater that contains one million bacteria in every milliliter, yet fewer that 0.1% of those bacteria are the V. fischeri symbiont. Nonetheless, communication between host and microbe lead to host colonization exclusively by V. fischeri. We are interested in the molecular signal transduction pathways that underlie the specifcitiy.  We have previously demonstrated the importance of the acquisition of the biofilm regulator, RscS, in squid colonization by North Pacific Ocean symbionts. We are following up on those studies to examine how regulatory pathways evolve to facilitate new microbe-host relationships and to determine how they are retained during changes in genome content.

Learn more about our study system


Euprymna scolopes squid are colonized by a single species of bacteria,
Vibrio fischeri (video courtesy of Siouxsie Wiles, University of Auckland)