CAREER: Understanding Spatial Heterogeneity in Biofilms Using Colloidal Engineering

职业：利用胶体工程了解生物膜的空间异质性

• 批准号: 2328766
• 负责人: Connie Chang
• 金额: $ 50万
• 依托单位: Mayo Clinic Rochester
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2328766&HistoricalAwards=false
• 关键词: CAREER; Understanding; Spatial; Heterogeneity; Biofilms

Non-Technical Abstract:Many microorganisms, including bacteria and algae, form thin films on surfaces known as biofilms. Examples of these include dental plaque, the slime that forms on ship hulls, and wound-associated infections. Biofilms contain millions of microscopic cells, and the individual locations of these cells affect their ability to function. For example, the location of cells within a wound-associated biofilm affects their ability to resist antibiotics. To understand how cell location affects function, their locations must be controlled in three dimensions; however, because the microorganisms within a biofilm are microscopically small, they are difficult to manipulate at a single cell level. This CAREER award by the Biomaterials program in the Division of Materials Research to Montana State University, Bozeman, supports the investigation of biofilm structure and function by building biofilms from microscopic modules that can be assembled, disassembled, and analyzed in a controlled manner. This approach will enable researchers to synthetically construct multi-species biofilms in the laboratory to understand how bugs communicate, cooperate, or compete. The proposed work will benefit society as a whole by uncovering the physical mechanisms behind microbial virulence and antibiotic resistance. This understanding can lead to new methods that will aid in controlling these persistent, surface-associated microbial colonies. Impact in the state of Montana will be provided by a "Soft Materials Shop" (SMASH), which will be used for both outreach and teaching, and will strengthen the connection of sciences, engineering, architecture, and art on campus. This space will be the first in the state of Montana and will be accessible to the public. This proposal will help prepare Montana students for future careers in STEM using inquiry-based learning strategies and hands-on demos, educate the public about microfabrication and engineering, and provide opportunities for outreach that will engage public audiences from youth to adults. Technical AbstractBiofilms are ubiquitous in the natural world, are formed by nearly all microorganisms, including algae, bacteria, archaea, and can be both beneficial and harmful. The spatial locations of microbes in a biofilm impact biofilm function and physiology; however, methods for structuring biofilms in three dimensions are currently lacking. The ability to synthetically construct a heterogeneous, multi-species biofilm by placing microorganisms in discrete locations within a cultivated environment would allow researchers to bridge this gap and explore how bugs communicate, cooperate, or compete. To achieve this, colloidal engineering techniques will be applied to place microbes in spatially organized three-dimensional locations to understand how spatial heterogeneity influences structure-function relationships in biofilms. The aims of this proposal are to create monodisperse capsules of gels and shells to encapsulate microbes, to assemble capsules into three-dimensional structures, and finally to create modular synthetic consortia of bacteria to explore questions related to heterogeneity in biofilms. These constructs will be used to understand how biofilm behavior such as quorum sensing, matrix formation, and dormancy arises from heterogeneity in biofilms. This CAREER award by the Biomaterials program in the Division of Materials Research to Montana State University, Bozeman, will support the integration of soft matter science into classes, workshops, demonstrations, and tours within a dedicated space called "SMASH", the creation of K-8 after-school outreach modules, and an undergraduate/graduate course on "Soft Matter Engineering". This award will allow for creative, multidisciplinary collaboration, bringing together students in art, architecture, engineering, and science on campus to create, prototype, design, and build. The ideas, workshops, and demonstrations created in this space will be incorporated into current K-8 outreach efforts and extended to future outreach efforts to introduce soft matter science, a relatively young area of research, to students and the general public.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.

非技术摘要：许多微生物，包括细菌和藻类，在表面形成薄膜，称为生物膜。例如，牙菌斑、船体上形成的粘液以及伤口相关感染。生物膜含有数百万个微观细胞，这些细胞的各个位置会影响它们的功能。例如，伤口相关生物膜内细胞的位置会影响它们抵抗抗生素的能力。为了了解细胞位置如何影响功能，必须在三个维度上控制它们的位置；然而，由于生物膜内的微生物在显微镜下很小，因此很难在单细胞水平上进行操作。该职业奖由蒙大拿州立大学博兹曼分校材料研究部生物材料项目颁发，通过利用可以以受控方式组装、拆卸和分析的微观模块构建生物膜来支持生物膜结构和功能的研究。这种方法将使研究人员能够在实验室中综合构建多物种生物膜，以了解细菌如何沟通、合作或竞争。拟议的工作将通过揭示微生物毒力和抗生素耐药性背后的物理机制使整个社会受益。这种理解可以带来新的方法，有助于控制这些持久的、与表面相关的微生物菌落。蒙大拿州的影响力将由“软材料商店”（SMASH）提供，该商店将用于外展和教学，并将加强校园内科学、工程、建筑和艺术的联系。 该空间将是蒙大拿州的第一个空间，并向公众开放。该提案将帮助蒙大拿州学生使用基于探究的学习策略和实践演示为未来的 STEM 职业做好准备，教育公众有关微制造和工程的知识，并提供外展机会，吸引从青少年到成人的公众受众。技术摘要生物膜在自然界中无处不在，由几乎所有微生物形成，包括藻类、细菌、古细菌，既有益又有害。生物膜中微生物的空间位置影响生物膜的功能和生理学；然而，目前缺乏在三个维度上构建生物膜的方法。通过将微生物放置在培养环境中的离散位置来合成构建异质、多物种生物膜的能力将使研究人员能够弥合这一差距并探索细菌如何沟通、合作或竞争。为了实现这一目标，将应用胶体工程技术将微生物放置在空间组织的三维位置，以了解空间异质性如何影响生物膜中的结构功能关系。该提案的目的是创建凝胶和外壳的单分散胶囊来封装微生物，将胶囊组装成三维结构，最后创建模块化的细菌合成菌落，以探索与生物膜异质性相关的问题。这些构建体将用于了解生物膜行为（例如群体感应、基质形成和休眠）如何由生物膜的异质性引起。该职业奖由蒙大拿州立大学博兹曼分校材料研究部生物材料项目颁发，将支持将软物质科学整合到名为“SMASH”的专用空间内的课程、研讨会、演示和参观中，该空间是 K 的创建。 -8个课外拓展模块，以及“软物质工程”本科/研究生课程。该奖项将允许创造性的多学科合作，将艺术、建筑、工程和科学领域的学生聚集在校园里进行创造、原型、设计和建造。在这个空间中创造的想法、研讨会和演示将被纳入当前的 K-8 推广工作中，并扩展到未来的推广工作中，向学生和公众介绍软物质科学这一相对年轻的研究领域。该奖项反映了通过使用基金会的智力价值和更广泛的影响审查标准进行评估，NSF 的法定使命被认为值得支持。