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，在被称为生物膜的表面形成薄膜。这些问题的例子包括牙菌斑、船体上形成的粘液以及与伤口相关的感染。生物膜包含数以百万计的微小细胞，这些细胞的不同位置会影响它们的功能。例如，细胞在创伤相关生物膜中的位置会影响它们抵抗抗生素的能力。要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，由于生物膜中的微生物非常小，很难在单个细胞水平上进行操作。这一职业奖项由博兹曼蒙大拿州立大学材料研究部的生物材料计划颁发，通过用可以控制的方式组装、拆卸和分析的微型模块构建生物膜，支持对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，以了解细菌如何交流、合作或竞争。这项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。这种理解可以导致新的方法，有助于控制这些持久的、与表面相关的微生物菌落。在蒙大拿州的影响将由一个“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。这将是蒙大拿州的第一个空间，将向公众开放。这项提议将帮助蒙大拿州的学生使用探究式学习策略和动手演示为未来的STEM职业生涯做好准备，教育公众关于微制造和工程，并提供机会，吸引从年轻人到成年人的公众受众。技术摘要生物膜在自然界中无处不在，几乎由所有微生物组成，包括藻类、细菌、古菌，既有好处，也有坏处。微生物在生物膜中的空间位置影响着生物膜的功能和生理；然而，目前还缺乏三维结构生物膜的方法。通过在栽培环境中的离散位置放置微生物来合成构建异质、多物种生物膜的能力，将使研究人员能够弥合这一差距，并探索细菌如何交流、合作或竞争。为了实现这一点，胶体工程技术将被应用于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。这项提议的目的是创建单分散的凝胶和贝壳胶囊来包裹微生物，将胶囊组装成三维结构，最终创建细菌的模块化合成联合体，以探索与生物膜中的异质性相关的问题。这些结构将被用来理解生物膜的行为，如群体感应、基质形成和休眠是如何由生物膜中的异质性引起的。这项由博兹曼蒙大拿州立大学材料研究部的生物材料项目颁发的职业奖项，将支持将软物质科学整合到名为“sMash”的专用空间内的课堂、研讨会、演示和参观中，创建K-8课后拓展模块，以及“软物质工程”的本科生/研究生课程。这个奖项将允许创造性的、多学科的合作，将艺术、建筑、工程和科学领域的学生聚集在一起，在校园里创造、原型、设计和建造。在这一领域创造的想法、研讨会和演示将被纳入当前的K-8推广工作，并扩展到未来的推广努力，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NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。