Research Interests

Metabolic regulation in microbial biofuel producers

The production of biofuels from cellulosic biomass holds promise as a source of clean renewable energy that can reduce our dependence on fossil fuels. Attaining this goal will require engineered microorganisms capable of economical conversion of cellulosic biomass into biofuels. Effective microbe design relies on understanding the relevant metabolic pathways and their regulation, including how the integrated networks function as a whole. Current project in our lab integrate systems-level analyses, especially metabolomics, computational modeling, and genetic engineering to advance understanding of metabolism in a variety of emerging biofuel producing microorganisms, including Z. mobilis, C. thermocellum, S. cerevisiae, and others. Our main research objectives in this area are: 1) Systems-level analysis of metabolic regulation in biofuel producing microorganisms and 2) Engineering symbiotic microbial consortia for biofuel production.

Selected Publications

Metabolic Remodeling during Nitrogen Fixation in Zymomonas mobilis, Martien et. al

In Vivo Thermodynamic Analysis of Glycolysis in Clostridium thermocellum and Thermoanaerobacterium saccharolyticum Using 13 C and 2 H Tracers, Jacobson et. al

Systems-Level Analysis of Oxygen Exposure in Zymomonas mobilis: Implications for Isoprenoid Production, Martien et. al

Metabolic remodeling during B. subtilis biofilm development

Most bacteria naturally congregate to form complex communities called biofilms through an elaborate process that involves production of secreted polymeric substances, allowing cells to stick to each other and to surfaces while conferring protection against harsh environments. Bacterial biofilms are abundant in natural environments and play an important role in many clinical, industrial, and ecological settings. Due to the ubiquity and significant impacts of biofilms on human activities, there is a clear need to better understand the complex processes that control biofilm formation and development. Current projects in our lab investigate a critical but barely understood aspect of biofilms: cellular metabolism during biofilm development.

We hypothesize that dynamic remodeling of central carbon and nitrogen metabolism constitutes an essential component of the highly coordinated physiological response that takes place during biofilm development. Using Bacillus subtilis as a model organism, we leverage state-of-the-art systems-level metabolomic and proteomic approaches, microscopy, and quantitative computational modeling, to pursue the following objectives: 1) a systems-level quantitative understanding of how metabolism is remodeled during biofilm formation; 2) elucidation of driving regulatory mechanisms controlling metabolic remodeling during biofilm formation; 3) novel insights regarding metabolic heterogeneity within biofilm cell subpopulations; and 4) elucidation of the physiological relevance of major metabolic alterations during biofilm development. This research will advance our understanding of the underlying logic and unifying principles behind the complex signaling systems of biofilm regulatory networks and will provide a holistic and quantitative understanding of the role of metabolism in biofilm development.

Selected Publications

Metabolic Remodeling during Biofilm Development of Bacillus subtilis, Pisithkul et. al

Bile acid transformations by the human gut microbe

Within the last decade, the central role the gut microbiota plays in human health has become widely recognized. An important way in which gut microbes affects host physiology is through their ability to chemically modify bile acids produced by the host. Bile acids act as signaling molecules within the host by modulating activity of nuclear hormone receptors in liver and other tissues and can also modulate gut microbiota composition via selective antimicrobial properties. Changes to the bile acid pool by gut microbes therefore has the potential to affect physiology in these organs, nutrient absorption, drug metabolism, and susceptibility to infection by bacterial pathogens. However, fundamental aspects of this process are still poorly understood. In particular, the distribution of bile acid transforming activity within gut microbes remains largely unexplored and the effects on host physiology resulting from modifications in the bile pool resulting from bacterial action remain poorly understood. Projects in our lab aim to generate a systematic and quantitative understanding of bile acid transforming capabilities in gut microbes and advance our understanding of the molecular mechanisms by which modulation of BA pools by host microbes, via production of secondary bile acids, affect liver host physiology and metabolism.

Selected Publications

Dominant Bacterial Phyla from the Human Gut Show Widespread Ability To Transform and Conjugate Bile Acids, Lucas et. al