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.

项目摘要 合成生物学家还开发工具和方法来赋予微生物新的属性和行为 合成新产品的能力。然而，很少有报道，其中细菌作为组分 用于将生物信息传输到电子设备和从电子设备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， 线索，而设备是由电子和光子编程。促进生物/器械 十字路口改变了我们的生活（例如，EKG）。我们的目标是重新连接细菌，使其成为信息翻译器， 以一种有助于理解人类健康的方式来做这件事。 人类胃肠道微生物组本身通常被视为一个复杂的器官，影响体内平衡，并涉及 在许多人类疾病中。胃肠道几何形状复杂，其微环境变化很大。pH和氧 水平分别从最酸性到中性和从完全厌氧到氧饱和水平存在。那里 很少有方法能够在宏观上解决其信号传导，细胞生长和化学环境 长度比例然而，在过去的几年里，研究人员已经开发了用于询问GI的微型和中型系统。 道生物学囊内内窥镜检查首次实现了远程成像。在微尺度上，器官或动物芯片 这些方法提供了在用户控制的条件下对生物功能的首次访问。两种方法 将为人类疾病的诊断和治疗开辟新的途径。然而，这两种方法都缺乏以下能力： 以细胞长度尺度和真实的时间询问和调节生物信号。 拟议的研究将利用合成生物学来制造用于询问分子空间的“智能”水凝胶。的 这项研究的创新是“生物平版印刷术”的发展，其中将多糖， 掺杂氧化还原响应儿茶酚，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是良性的， 这些传感材料可以在几分钟内就地组装，而不需要额外的机械设备。迄今为止，在体外 微观和中尺度的器件都不能提供细胞长度和时间尺度上的分子信息， 审问这项工作的意义在于它对动物芯片系统，胶囊内窥镜设备， 以及其他方法，这些方法在推进疾病的诊断和治疗方面有很大的希望，但缺乏可及性， 分子线索和信息传递。