EFRI-MIKS: Innovations for Next Generation Biomanufacturing and Microengineering

EFRI-MIKS：下一代生物制造和微工程的创新

• 批准号: 1137249
• 负责人: Ranjan Srivastava
• 金额: $ 200万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1137249&HistoricalAwards=false
• 关键词: EFRI; MIKS; Innovations; Next; Generation

The interplay that occurs among microbes in their habitat allows the microbial community, or "microbiome", to carry out chemical processes exceeding that of any individual organism in the community. The successful execution of such complex processes requires a coordination of the metabolisms of the component species. Such coordination is accomplished by directly sending and receiving signals among members of the community. Some signals are indirect, such as those resulting from changes in the local environment caused by their metabolisms. By understanding these signaling processes, it may be possible to manipulate these communities and harness their capabilities on an industrial scale.The microbial community inside the gut of the lower termite represents one such community. Consisting of bacteria, archaea, and protists, the organisms in this community exist symbiotically, breaking down complex carbon sources, such as lignocellulose, to the benefit of all. The physical and chemical habitat of the termite gut varies at a spatial scale of microns and affects the structure and function of its microbial community. We hypothesize that the lignocellulosic processing capabilities of the termite gut community are dependent on its composition, the spatial distribution of its members, and their interactions. We further hypothesize that maintenance of the community is regulated through a complex signaling network composed of cell-cell contact dependent signaling and intercellular chemical signaling. By understanding how these processes function, it will be possible to harness the termite microbiome as a platform for chemical production. To test our hypotheses, we will reproduce the micro-scale physical and chemical features of a lower termite gut in manufactured microhabitats, i.e. artificial termite guts. We will pursue the following specific aims to accomplish our goal:1. Metagenomics: Evaluate the gut community of the lower termite Reticulitermes flavipes by sequencing DNA extracted from the entire community and analyzing those sequences.2. Signaling: Identify key signaling molecules and the organisms they interface with and examine the functions that they control.3. Modeling: Carry out mathematical analysis to determine the signaling network?s structure and control processes.4. Engineering: Develop a microfluidic culture array mimicking the microhabitat of the R. flavipes gut allowing physicochemical control and real time monitoring.5. Integration: Establish, maintain, and control a functional termite microbiome in vitro.Intellectual Merit. The transformative nature of this work lies in developing an understanding of the termite gut signaling network and using it to engineer a chemical production platform. A significant leap in engineering knowledge will be realized through the development of the artificial termite gut and our ability to rationally manipulate its microbial population. The microhabitat?s population will be manipulated by the introduction of appropriate signal molecules into its feed stream or through disruption of natural intercellular signals.Broader Impacts. The proposed research will address a national need by laying the groundwork for a new biofuels development platform. Our long-term strategy is to develop the microhabitat array for use in processing lignocellulose to a biofuel or to an intermediate compound for biofuel production, such as feedstock for other microorganisms capable of ethanol or butanol production. Additionally, we will carry out a number of outreach activities, including high school teacher training initiatives and local radio broadcasts about the research. To reach a wider audience, and to provide educational supplements, podcasts will be developed along with workshops & presentations at local museums. An iPod/iPad application and PC educational video game/educational tool about building an in silico functional termite microbiome will be created and made freely available in both English and Spanish. All computer code will be open sourced and made freely available.

微生物在其栖息地中发生的相互作用允许微生物群落或“微生物组”进行超过群落中任何个体生物的化学过程。这种复杂过程的成功执行需要组分物种的代谢的协调。这种协调是通过在社区成员之间直接发送和接收信号来实现的。有些信号是间接的，例如由其新陈代谢引起的当地环境变化所产生的信号。通过了解这些信号传导过程，我们有可能在工业规模上操纵这些群落并利用它们的能力，低等白蚁肠道内的微生物群落就是这样一个群落。该群落中的生物由细菌、古细菌和原生生物组成，共生存在，分解木质纤维素等复杂的碳源，造福于所有人。白蚁肠道的物理和化学生境在微米的空间尺度上变化，并影响其微生物群落的结构和功能。我们假设白蚁肠道群落的木质纤维素加工能力取决于其组成、成员的空间分布及其相互作用。我们进一步假设，社区的维护是通过一个复杂的信号网络组成的细胞-细胞接触依赖性信号和细胞间的化学信号调节。通过了解这些过程的功能，将有可能利用白蚁微生物组作为化学生产的平台。为了验证我们的假设，我们将复制一个较低的白蚁肠道制造的微生境，即人工白蚁肠道的微尺度的物理和化学特征。我们将努力实现以下具体目标：1.宏基因组学：通过对黄足散白蚁整个群落的DNA序列进行测序和分析，对黄足散白蚁肠道群落进行评价.信号传导：识别关键信号分子和它们与之相互作用的生物体，并检查它们控制的功能。建模：进行数学分析，确定信令网？的结构和控制过程.工程学：开发一种模拟R.黄足肠允许理化控制和真实的时间监测.整合：建立、维持和控制体外功能性白蚁微生物组。这项工作的变革性在于发展对白蚁肠道信号网络的理解，并利用它来设计化学生产平台。通过人工白蚁肠道的发展和我们合理操纵其微生物种群的能力，将实现工程知识的重大飞跃。微生境？通过将适当的信号分子引入其饲料流或通过破坏天然的细胞间信号来操纵的种群。拟议的研究将通过为新的生物燃料开发平台奠定基础来满足国家需求。我们的长期战略是开发微生境阵列，用于将木质纤维素加工成生物燃料或生物燃料生产的中间化合物，例如能够生产乙醇或丁醇的其他微生物的原料。此外，我们还将开展一些外联活动，包括高中教师培训活动和有关研究的当地电台广播。 为了接触到更多的观众，并提供教育补充，将沿着在当地博物馆举办研讨会和演讲。一个iPod/iPad应用程序和PC教育视频游戏/教育工具，关于建立一个在硅片功能白蚁微生物组将创建和免费提供英语和西班牙语。所有的计算机代码都将开源并免费提供。