Collaborative Research: MIM: Learning how mucus shapes and maintains microbiomes

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Mucus, the slimy gel that lines all wet surfaces in our bodies, is a key ecological niche for microbiomes: It accommodates an incredible 100 trillion microbes, somehow selecting for helpful microbes while controlling problematic pathogens. Moreover, it does so in disparate organisms ranging from the simplest animals to corals, snails, fish, and frogs. Yet, it is still not known what enables microbial communities to grow and function so effectively inside mucus. New evidence suggests that the sugar-coated molecules that form mucus shape microbiomes through physical, chemical, and nutritive interactions. This hypothesis will be tested by addressing three questions: What properties of mucus do microbes care about? How are microbes structured in mucus -- who is next to whom and why? And, what are the processes by which microbiomes self-organize in mucus? This work combines the distinct and complementary expertise of three scientists specializing in mucus biochemistry, microbiome structure and molecular biology, and the biophysics of microbe-mucus interactions. Understanding how mucus controls microbiomes could yield new strategies for protecting humans from infections, as well as for leveraging beneficial microbes that can help humans and animals thrive in other ways such as by improving food digestion and salt tolerance. The investigators will also develop new citizen science initiatives and demonstrations, integrate research and education, and engage students and teachers to help create a diverse community of researchers and change the perception of mucus from a slimy waste product to a fascinating biomaterial with critical biological functions.Mucus is a critically important habitat for microbes. Despite its pivotal importance to human and animal functioning, however, the mechanisms by which mucus interacts with microbiomes are not understood. Indeed, mucus interacts with microbes in two seemingly conflicting ways, maintaining a dense and diverse healthy microbiome while simultaneously clearing and disarming harmful microbes. This research team will unravel this puzzle by investigating the mechanisms underlying this key Rule of Life, with the hypothesis that mucus shapes microbiomes through physical, chemical, and nutritive interactions. To test this hypothesis, the investigators will (I) Evaluate how mucin glycans--the chains of different sugars that decorate mucin proteins-- select for specific microbes in natural communities, (II) Identify the influence of different mucus components on the intricate spatial structure of complex microbial communities, and (III) Determine the mechanisms by which mucus regulates microbial community assembly. By revealing the biochemical and biophysical mechanisms by which mucins influences microbial community structure (both taxonomic and spatial), this work will elucidate the essential role played by mucus as an ecological habitat that supports the growth of beneficial commensal microbes while also preventing the outgrowth of pathogens. The results will also benefit society by informing applications that seek to engineer mucus-inspired materials to control environmental and organismal microbiomes. This work will also inspire new educational and outreach efforts for all ages to improve public awareness of the topic of “mucus and microbiomes”. This project was co-funded by the Division of Materials Research in the Mathematical and Physical Sciences Directorate, and by the Symbiosis, Infection and Immunity group in the Division of Integrative Organismal Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.