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Molecular Analysis and Engineering of the Human Microbiome

Stanford ChEM-H solicited proposals from Stanford faculty members who are interested in the interdependency of gut microbiota and human health and seek to develop or apply molecular tools and thought processes to interrogate and engineer this complex but essential relationship.

Proposals were solicited through two phases. In the first phase, eight faculty collaborators identified as co-investigators on the six highest ranked proposals were each provided with a small amount of seed funding with the goal of intermixing the faculty members to promote community and collaboration among the broader group. In the second phase, two proposals were selected from a competitive pool of applciations for one year of funding beginning in November 2016.

Phase I Investigators:

Ami Bhatt, Medince and Genetics
Joshua Elias, Chemical & Systems Biology
Polly Fordyce, Genetics and Bioengineering
Christopher Gardner, Medicine
K.C. Huang, Bioengineering
Timothy Meyer, Medicine
Elizabeth Sattely, Chemical Engineering
Justin Sonnenburg, Microbiology & Immunology

Phase II Selected Projects:

"Proteomic Tools to Discover Non-Host GI Antigens Presented to the Adaptive Immune System"

Principal Investigators:

Joshua Elias, Chemical & Systems Biology
Justin Sonnenburg, Microbiology & Immunology

Project Summary:

Research describing how we should cultivate “good bacteria” in our gastrointestinal tracts (GI), and the dangers of gluten in our diets are reported daily in the news. Although we know that GI bacteria and the food we eat have strong influences on our immune systems, the mechanisms by which they do this is almost always unknown. Although active immune systems are critical for fighting infections and cancer, inappropriate immune activation can lead to diseases like diabetes and multiple sclerosis. Therefore, it remains critically important to discover how our immune systems are tuned by GI bacteria and our diets at the molecular level. Our research will accomplish this using mass spectrometry technologies invented in the Elias Lab, and specialized mouse models that will let us examine specific foods and bacteria for their ability to be seen by specialized cells in the immune system (T-cells). Our method will show us exactly which bacteria- or food-derived proteins are capable of shaping our immune systems. We envision this knowledge could lead to new “smart” probiotic pills, containing specialized microbes capable of delivering the exact molecules that activate or pacify a person’s immune system as needed, to prevent and fight disease.

This award was made in partnership with the Institute for Immunity, Transplantation, and Infection (ITI), which has provided funds to support the use of their Human Immune Monitoring Center.


"Defining the Role of Gut Microbes in Activating Plant Nutrients and Impact on Host Biology"

Principal Investigators:

Elizabeth Sattely, Chemical Engineering
Justin Sonnenburg, Microbiology & Immunology

Project Summary:

Diet is a key environmental factor that influences human health and disease risk. Various nutrients from dietary plants have been linked to disease prevention; importantly, their absorption in the intestine often depends on biochemical processing by gut bacteria. It is known that human gut bacterial communities differ markedly in their ability to process certain plant-derived nutrients; as a result, two people eating the same meal are thought to absorb different quantities of key nutrients. However, the molecular details of this phenomenon (which bacterial species and enzymes do the processing) are not well understood, nor has the extent of bacterial nutrient ‘liberation’ been explored. The goal of this proposal is to study the gut bacterial processing of an important class of plant-derived nutrients known as glucosinolates, which are abundant in cruciferous vegetables such as broccoli and cabbage. Here, we will perform experiments in mice colonized by a single bacterial species to show that an individual bacterial operon controls the level of glucosinolate metabolites absorbed by the host, and to discover additional plant-derived chemicals processed by the same enzymatic system. In addition, we will use isotope-labeled plants to broadly characterize liberation of dietary small molecules by the gut microbiota in an effort to better quantify the impact of diet on health.