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February 8, 2023
12:00pm, PST 1100 Terasaki Life Sciences Building (TLSB)
University of Wisconsin-Madison
" Predicting and designing the human gut microbiome "
The human gut microbiome substantially expands our genome’s capabilities and is a critical determinant of our health. In a healthy state, this gut ecosystem can provide beneficial functions. However, due to contrasting evolutionary objectives, disruptions to this ecosystem can alter the composition and functions of the community, which in leads to deleterious impacts on human health. Precision engineering of the gut microbiome holds tremendous therapeutic potential for personalized medicine. However, the complexity of this system including the hundreds of diverse bacterial species that reside in the gut, variability in the composition across individuals and unpredictable dynamic responses to environmental inputs have precluded our ability to effectively manipulate this system to our benefit. A detailed, mechanistic and quantitative understanding is critical for precisely manipulating the human gut microbiome. We seek to decipher the web of cellular interactions and molecular and ecological mechanisms driving the dynamic behaviors of gut microbiota. The ecological and molecular mechanisms will be exploited as novel control knobs to steer the system towards desired metabolic states.
By combining high-throughput bottom-up assembly of human gut communities with computational modeling, we decipher the interaction networks shaping community dynamics and health-relevant functions. We exploit the data-driven models to design communities with desired behaviors including tailored metabolite profiles and enhanced resistance to invasion by human gut pathogens. We demonstrate that complex dietary fibers can enhance the stability and resilience of human gut communities to perturbations by reducing the prevalence of negative inter-species interactions and promoting metabolic diversity. Since single-cells exhibit heterogeneity within the gut microbiome, we develop high-throughput capabilities to profile the extent of heterogeneity, providing deeper insights into the key determinants of phase variation in human gut symbionts. In sum, our work provides a foundation for exploring and exploiting the structure-function landscapes of microbiomes.
Host: Nandita Garud