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

合作研究：MIM：了解粘液如何塑造和维持微生物组

• 批准号: 2245229
• 负责人: Jessica Mark Welch
• 金额: $ 80万
• 依托单位: The Forsyth Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2245229&HistoricalAwards=false
• 关键词: Collaborative; Research; MIM; Learning; how

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.

粘液是将我们体内所有湿表面的粘合凝胶排列的粘合凝胶，是微生物组合的关键生态生态位：它可容纳令人难以置信的100万亿微生物，以某种方式选择有用的微生物，同时控制有问题的病原体。此外，它在不同的生物中这样做，从最简单的动物到珊瑚，蜗牛，鱼和青蛙。然而，尚不清楚什么使微生物群落在粘液内部如此有效地生长和发挥作用。新的证据表明，通过物理，化学和营养相互作用形成粘液形成微生物的糖包被的分子。该假设将通过解决三个问题来检验：微生物关心粘液的特性？微生物是如何在粘液中结构的 - 谁是谁，为什么？而且，微生物组在粘液中进行自组织的过程是什么？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独特和完全专业的知识。了解粘液如何控制微生物组可以产生保护人类免受感染的新策略，以及利用有益的微生物，这些微生物可以帮助人类和动物以改善食物消化和耐盐性来以其他方式繁荣发展。研究人员还将开发新的公民科学计划和演示，综合研究和教育，并吸引学生和老师，以帮助建立一个由研究人员组成的潜水社区，并将粘液的感知从粘糊糊的废物产品转变为具有关键生物学功能的迷人生物材料。粘液是微生物至关重要的栖息地。尽管对人类和动物功能的重要性至关重要，但是却不了解粘液与微生物组相互作用的机制。确实，粘液以两种看似相互矛盾的方式与微生物相互作用，保持着密集和潜水的微生物组，同时清除并解除有害微生物的武装。该研究团队将通过研究这一关键生活规则的机制来揭示这一难题，并假设粘液通过物理，化学和营养相互作用来塑造微生物组。 To test this hypothesis, the investigators will (I) Evaluate how mutin glycans--the chains of different sugars that decorate mutin 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.通过揭示粘蛋白影响微生物群落结构（分类学和空间）的生化和生物物理机制，这项工作将阐明粘液作为一种生态栖息地所起的基本作用，该生态栖息地支持有益的致密微生物的增长，同时还可以防止病原体的产生。结果还将通过告知寻求设计粘液启发的材料以控制环境和有机微生物组的应用程序来使社会受益。这项工作还将激发所有年龄段的新教育和推广工作，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局的材料研究部共同资助，并由综合有机体系统部门的共生，感染和免疫小组共同资助。该奖项反映了NSF的法定任务，并被认为是通过评估基金会的智力和更广泛的影响来通过评估来获得支持的珍贵。