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

黏液是黏稠的凝胶，分布在我们身体所有潮湿的表面，是微生物群落的关键生态位：它容纳了令人难以置信的100万亿微生物，在控制问题病原体的同时，以某种方式选择有益的微生物。此外，它在不同的生物中也会这样做，从最简单的动物到珊瑚、蜗牛、鱼和青蛙。然而，人们仍然不知道是什么使微生物群落在粘液中如此有效地生长和发挥作用。新的证据表明，形成黏液的糖包分子通过物理、化学和营养相互作用形成微生物群。这一假设将通过解决三个问题来验证：微生物关心粘液的哪些特性？粘液中的微生物是如何构成的——谁挨着谁，为什么挨着谁？微生物群在粘液中自我组织的过程是什么？这项工作结合了三位专门从事粘液生物化学，微生物组结构和分子生物学以及微生物-粘液相互作用的生物物理学的科学家的独特和互补的专业知识。了解粘液如何控制微生物群可以产生新的策略来保护人类免受感染，以及利用有益微生物来帮助人类和动物以其他方式茁壮成长，例如通过改善食物消化和耐盐性。研究人员还将开发新的公民科学倡议和示范，将研究和教育结合起来，并让学生和教师参与进来，帮助创建一个多样化的研究人员社区，并将粘液从一种粘稠的废物转变为一种具有关键生物学功能的迷人生物材料。粘液是微生物极其重要的栖息地。然而，尽管粘液对人类和动物的功能至关重要，但其与微生物群相互作用的机制尚不清楚。事实上，粘液以两种看似矛盾的方式与微生物相互作用，在保持密集和多样化的健康微生物群的同时，清除和解除有害微生物。这个研究小组将通过研究这一关键生命法则背后的机制来解开这个谜团，并假设粘液通过物理、化学和营养的相互作用来塑造微生物群。为了验证这一假设，研究人员将(I)评估粘蛋白聚糖（修饰粘蛋白的不同糖链）如何在自然群落中选择特定微生物，（II）确定不同粘液成分对复杂微生物群落复杂空间结构的影响，以及（III）确定粘液调节微生物群落组装的机制。通过揭示黏液蛋白影响微生物群落结构的生化和生物物理机制（包括分类和空间），这项工作将阐明黏液作为生态栖息地所发挥的重要作用，它支持有益共生微生物的生长，同时也阻止病原体的生长。这一结果也将造福于社会，因为它将为寻求设计以黏液为灵感的材料来控制环境和有机微生物群的应用提供信息。这项工作还将激发针对所有年龄层的新的教育和宣传工作，以提高公众对“粘液和微生物组”主题的认识。该项目由数学和物理科学理事会材料研究部以及综合有机体系统部的共生、感染和免疫组共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.