Full Name

Jessica Mark Welch

Using Spatial Structure to Understand Microbial Community Function

Bacteria play a critical role in both human health and the functioning of healthy ecosystems. In the human body, bacteria are necessary for normal development and function.  Microbes in the mouth colonize densely on all available surfaces, including the teeth as well as the gums, tongue, and tonsils where bacteria interact directly with human tissues and the human immune system. Gut bacteria function as a digestive organ that provides energy and essential nutrients to the human body and produces a huge array of metabolic products. Understanding the structure and function of these bacterial communities in the human body is critical to improving human health and developing personalized medicine.

In natural ecosystems, bacteria make up a large fraction of the total biomass, carrying out chemical transformations that influence, for example, the fate of carbon dioxide and nitrogen in the environment. Understanding these microbial ecosystems is critical to predicting and mitigating the outcomes of climate change. Microbes also play a key role in the physiology of keystone species on which the health of an ecosystem (e.g. a salt marsh) depends.

A key limitation in understanding microbial communities is the near-total absence of information on their micron-scale spatial structure. Microbes that are touching or located within a few micrometers of each other can acquire properties that they do not have independently, such as the ability to survive in an aerobic environment or invade a host cell and evade the host immune response. Therefore, to understand the properties of these microbes it is critical to know who their immediate neighbors are. Much information about complex microbial communities has been learned from DNA sequencing approaches, but the process of homogenizing the sample for DNA extraction destroys critically important spatial information.

My research program focuses on analyzing the spatial organization of microbial communities. My colleagues and I have developed a method that gives us the unique ability to simultaneously image and identify dozens of microbial taxa, using a technique we call Combinatorial Labeling and Spectral Imaging – Fluorescence in situ Hybridization (CLASI-FISH). Using CLASI-FISH we are analyzing the spatial structure of bacteria in the human mouth, with the goal of understanding the normal structure and function of these communities in health and its disturbance in disease. We have also the method to studies of the microbes living on kelp, in the gut of cuttlefish, on marine plastic debris, and in gnotobiotic mice  as a simplified model system of the human gut microbiota.

An article by Ed Yong about our work on the spatial organization of the plaque microbiome is here.

An article by Carl Zimmer about our work on oligotyping the oral microbiome is here.

Spatial Organization of the Oral Microbiome

The human oral microbiome consists of more than 700 bacterial species. In collaboration with Gary Borisy and Floyd Dewhirst of the Forsyth Institute, we are employing CLASI-FISH to investigate the spatial organization of the dental plaque biofilm as well as the microbiome on the tongue and other oral surfaces. In dental plaque we discovered an extraordinarily complex and highly organized microbial consortium, which we named a “hedgehog,” organized around filamentous corynebacteria. Within the structure, individual taxa are localized at the micron scale in ways suggestive of their functional niche in the consortium. The hedgehog consortium illustrates how complex structural organization can emerge from micron-scale interactions of the constituent organisms.

Spatial Organization of Microbiomes of Marine Organisms

Microbes are key to the biology and adaptation of many of the diverse organisms found in the waters around Woods Hole and around the globe. Spatial organization gives us clues to the functional roles of microbes and their relationship to their hosts. In collaboration with Cathy Pfister (https://pfisterlab.uchicago.edu/) of the University of Chicago, we are investigating the organization of the microbes living on seaweeds, a diverse group of algae that evolved multicellularity more than a billion years ago in an ocean populated by diverse microbial lineages. In particular, we have investigated the microbial community of kelp, an important ecosystem engineer and foundational taxon in the kelp forests of the Pacific coast of North America.