Accessing molecular communication via synthetic biology and microelectronics – gut on a chip model

通过合成生物学和微电子学 - 芯片模型肠道进行分子通讯

• 批准号: 9455959
• 负责人: WILLIAM E. BENTLEY
• 金额: $ 22.52万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-22 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9455959
• 关键词: Address; Anaerobic Bacteria; Animals; Bacteria; Behavior; Benign; Biological; Biological Process; Biology; Catechols; Cells; Chemical Engineering; Chemicals; Chitosan; Coculture Techniques; Communication; Communities; Complex; Cues; DNA Microarray Chip; Development; Device Designs; Devices; Diagnosis; Diagnostic; Disease; Dopa; Electrocardiogram; Electrodes; Electronics; Electrons; Elements; Endoscopy; Engineering; Environment; Enzyme Activation; Enzymes; Epithelial Cells; Equipment; Escherichia coli; Feedback; Film; Gastrointestinal tract structure; Gene Expression; Genetic; Geometry; Glucose; Goals; Health; Homeostasis; Human; Hydrogels; Hydrogen Peroxide; Image; In Situ; In Vitro; Intestines; Ions; Language; Length; Link; Liquid substance; Measurement; Measures; Mechanics; Mediating; Mediator of activation protein; Methodology; Methods; Microfabrication; Microfluidic Microchips; Microfluidics; Modeling; Molecular; Molecular Probes; Mono-S; Nature; Optics; Organ; Output; Oxidation-Reduction; Oxides; Oxygen; Performance; Phenotype; Photons; Polysaccharides; Process; Proteins; Pseudomonas aeruginosa; Pyocyanine; Reporting; Reproducibility; Research Personnel; Resolution; Sampling; Sepharose; Signal Transduction; Signaling Molecule; Specificity; Speed; System; Systems Integration; Technology; Testing; Time; VAI-2; Work; base; beta-Galactosidase; biofabrication; biological systems; calginat; cell growth; design; drug discovery; flexibility; glucose monitor; glucose oxidase; gut microbiome; human disease; innovation; insight; lithography; microorganism; molecular recognition; novel; quorum sensing; response; sensor; spatiotemporal; synthetic biology; tool; uptake

PROJECT SUMMARY Synthetic biologists develop tools and approaches to endow microorganisms with novel attributes and behaviors, as well as the ability to synthesize novel products. There have been few reports, however, wherein bacteria serve as components of devices created to transmit biological information to and from electronic devices. Information flow between biological systems and electronic devices is complicated by the fact that most of biological function is mediated by molecular or ionic cues, while devices are programmed by electrons and photons. Technologies that have facilitated the bio/device intersection have changed our lives (e.g., EKG). Our objective is to rewire bacteria to serve as information translators and to do this in a way that facilitates understanding of human health. The human gastrointestinal microbiome, often viewed as a complex organ itself, influences homeostasis and is implicated in many human diseases. GI tract geometry is complex and its microenvironments are widely varied. pH and oxygen levels exist from the most acidic to neutral, and from completely anaerobic to oxygen saturation levels, respectively. There are few methodologies that enable resolution of its signaling, cell growth, and chemical environments even at the macro length scale. In the last several years however, researchers have developed micro and meso systems for interrogating GI tract biology. Capsular endoscopy has enabled first-of-kind remote imaging. At the microscale, organ or animal-on-a-chip methodologies provide first-of-their kind access to biological function in user-controlled conditions. Both methodologies will open new avenues for diagnosis and treatment of human disease. Both methodologies, however, lack the ability to interrogate and modulate biological signaling at cellular length scales and in real time. The proposed studies will enlist synthetic biology to create `smart' hydrogels for interrogating molecular space. The innovation of this proposed study is the development of `biological lithography', where polyelectrolyte polysaccharides, doped with redox responsive catechols, will be layered with engineered cells for an expanded repertoire of molecular recognition and information transfer. Importantly, fabrication methodologies are simple and biologically benign so that these sensing materials can be assembled in situ in minutes and with no added mechanical equipment. To date, in vitro devices at both micro and meso scale do not provide molecular information at the length and time scales of the cells they interrogate. The significance of this work is its complementarity to animal-on-a-chip systems, capsular endoscopy devices, and other methodologies that have great promise for advancing diagnosis and treatment of disease but that lack access to molecular cues and information transfer.

项目概要 合成生物学家还开发了赋予微生物新属性和行为的工具和方法 作为合成新产品的能力。然而，以细菌作为成分的报道却很少。 用于在电子设备之间传输生物信息的设备。生物之间的信息流 由于大多数生物功能是由分子或离子介导的，系统和电子设备变得复杂 线索，而设备则由电子和光子编程。促进生物/设备发展的技术 交叉点改变了我们的生活（例如心电图）。我们的目标是重新连接细菌，使其充当信息翻译者和 以促进了解人类健康的方式做到这一点。 人类胃肠道微生物组本身通常被视为一个复杂的器官，它影响体内平衡并与 在许多人类疾病中。胃肠道的几何形状很复杂，其微环境也多种多样。 pH值和氧气 分别存在从最酸性到中性以及从完全厌氧到氧饱和度的水平。那里 即使在宏观上，也很少有方法能够解决其信号传导、细胞生长和化学环境 长度尺度。然而，在过去几年中，研究人员开发了用于询问胃肠道的微观和细观系统 道生物学。胶囊内窥镜首次实现了远程成像。在微观尺度、器官或动物芯片上 该方法首次提供了在用户控制的条件下获取生物功能的途径。两种方法论 将为人类疾病的诊断和治疗开辟新途径。然而，这两种方法都缺乏能力 在细胞长度尺度上实时询问和调节生物信号。 拟议的研究将利用合成生物学来创建用于探究分子空间的“智能”水凝胶。这 这项拟议研究的创新之处在于“生物光刻”的发展，其中聚电解质多糖， 掺杂有氧化还原反应性儿茶酚，将与工程细胞分层，以扩大分子库 识别和信息传递。重要的是，制造方法简单且生物学上无害，因此 这些传感材料可以在几分钟内就地组装，无需添加机械设备。迄今为止，在体外 微观和介观尺度的设备不提供其细胞的长度和时间尺度的分子信息 审问。这项工作的意义在于它与动物芯片系统、胶囊内窥镜设备、 以及其他在推进疾病诊断和治疗方面大有希望但缺乏可及性的方法 分子线索和信息传递。