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.

粘液是一种粘糊糊的凝胶，排列在我们身体的所有潮湿表面上，是微生物组的一个关键生态位：它容纳了令人难以置信的100万亿个微生物，以某种方式选择有益的微生物，同时控制有问题的病原体。此外，它在从最简单的动物到珊瑚、蜗牛、鱼和青蛙的不同生物体中也是如此。然而，仍然不知道是什么使微生物群落能够在粘液中如此有效地生长和发挥作用。新的证据表明，形成粘液的糖衣分子通过物理，化学和营养相互作用形成微生物组。这一假设将通过解决三个问题来检验：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--谁在谁旁边，为什么？微生物组在粘液中自我组织的过程是什么？这项工作结合了三位科学家的独特和互补的专业知识，他们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。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计划和示范，整合研究和教育，并让学生和教师参与进来，帮助创建一个多元化的研究人员社区，并将粘液从粘糊糊的废物转变为具有重要生物功能的迷人生物材料。粘液是微生物的重要栖息地。 尽管它对人类和动物的功能至关重要，然而，粘液与微生物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，保持密集和多样化的健康微生物组，同时清除和消除有害微生物。该研究小组将通过调查这一关键生命规则的机制来解开这个谜团，假设粘液通过物理，化学和营养相互作用塑造微生物组。为了验证这一假设，研究人员将（I）评估粘蛋白聚糖-装饰粘蛋白蛋白的不同糖链-如何选择自然群落中的特定微生物，（II）确定不同粘液组分对复杂微生物群落的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。通过揭示粘蛋白影响微生物群落结构（分类和空间）的生化和生物物理机制，这项工作将阐明粘液作为支持有益微生物生长的生态栖息地所发挥的重要作用，同时也防止病原体的生长。研究结果还将通过为寻求工程粘液启发材料以控制环境和生物微生物组的应用提供信息而造福社会。这项工作还将激发针对所有年龄段的新的教育和外联工作，以提高公众对“粘液和微生物组”专题的认识。该项目由数学和物理科学理事会材料研究部和综合有机系统部的共生、感染和免疫小组共同资助。该奖项反映了NSF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。