1. New genetic tools for the human microbiota. We have developed the first CRISPR-Cas9 based genetic system for a Clostridium commensal Clostridium sporogenes. We are interested in applying the CRISPR-Cas9 technology to other gut bacteria that have shown a strong correlation with human health and disease but are currently not genetically tractable.
2. Modulating microbiota metabolites in the host and study their effects on host biology. An increasing number of studies are revealing important connections between microbiome-derived metabolites and human diseases like inflammatory bowel disease and colon cancer. We will focus on a group of molecules that are derived via microbial fermentation of nutrients (e.g. propionate and butyrate). These molecules are highly abundant and circulatory (have body-wide effects) in the body and their levels can be manipulated via genetic engineering of the gut microbiome. We will apply the genetic tools in the lab to toggle on/off these microbiota metabolites in vivo and investigate their effects on host intestinal immunity and IBD development.
3. Regulating the metabolic interaction between host and gut microbiota. The microbiome is one of the key orchestrators in mediating human health. We will use bioinformatics and molecular genetics to design and engineer a microbiota community for a predefined function in regulating host intestinal immunity for IBD treatment.