BME Seminar: Xiaofan Jin
Monday, September 18th, 2023 - 12:00 p.m.
Xiaofan Jin, Ph.D.
Bioinformatics Fellow
Gladstone Institutes
"Tracking Ecology and Evolution of Gut Microbial Communities Across Space and Time"
Keating 103 | Zoom link
Hosts: Dr. Mario Romero-Ortega and Dr. Shang Song
(Instructor permission required for enrolled students to attend via Zoom)
Persons with a disability may request a reasonable accommodation by contacting the Disability Resource Center at 621-3268 (V/TTY).
Abstract:
The behavior of microbial communities such as the human gut microbiome depends on both their taxonomic composition as well as spatial structure. While fecal metagenomic sequencing has successfully revealed the rich diversity of microbes found in our guts, we remain largely unaware of how these microbial communities are spatially organized between different gut regions such as lumen and mucosa, and how this structure affects community function and human health. To address this, we develop a spatially-resolved gutmicrobiome culture platform, incorporating synthetic mucosal surfaces with liquid-phase culture to simulatemucosa-lumen structure in vivo. This approach uses a complex synthetic community comprising over one hundred prevalent gut strains, with high quality genomes to enable accurate strain level profiling of community abundances using shotgun metagenomic sequencing. Independently sampling surface-attached and liquid-phase communities over time, we demonstrate that incorporation of synthetic mucosal surfaces yields a more diverse community than traditional liquid culture, allowing co-existence of closely related strains. Distinct enrichment patterns emerge with specific strains enriched for surface-attachment over liquid-phase and vice versa, including cases where closely related strains exhibit divergent spatial enrichment phenotypes. Applying phylogenetically aware statistical models, we use this data to predict microbial genetic factors underlying this spatial organization, suggesting an important role for several categories of gene families -- including lipo/exopolysaccharidebiosynthesis, transcriptional regulation, membrane transporter, and membrane proteases -- in determining mucosa-lumen gut community structure. We additionally use metagenomic sequencing data to track real-time evolutionary changes within our microbial community and find evidence of differential selective pressure associated with surface-attachment in the form of de novo mutations, horizontal gene transfer, and genomicinversions. Collectively, these findings reveal that spatial structure plays a key role in determining the eco-evolutionary dynamics of gut microbial communities.
Bio:
Xiaofan Jin is a bioinformatics fellow at the Gladstone Institutes, and previously received his Ph.D. in bioengineering from Stanford University. His research interests revolve around the structure-function relationship of microbial communities, in particular those associated with health and disease such as the gut microbiome. His work integrates bioinformatic and synthetic biology approaches to interrogate, manipulate, and ultimatelyreprogram these microbial communities to improve human health.