SemiSynBio: Redox-enabled Bio-Electronics for Molecular Communication and Memory (RE-BIONICS)

SemiSynBio：用于分子通信和记忆的氧化还原生物电子学（RE-BIONICS）

• 批准号: 1807604
• 负责人: William Bentley
• 金额: $ 112.5万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807604&HistoricalAwards=false
• 关键词: SemiSynBio; Redox; enabled; Bio; Electronics

The goal of the RE-BIONICS project (Redox-enabled Bio-Electronics based on Molecular Communication) is to create first-of-kind bioelectronics devices that will mediate the rapid and facile information exchange between biology and electronics. These devices will have the potential to transform healthcare, enabling tele-monitoring and remote/autonomous drug delivery and facilitating environmental monitoring in agriculture and cyber-defense where connecting biological phenomena with electronics are important. The technical underpinnings of this work recognize that microelectronic devices depend on electrons for information processing while biology depends on molecules (e.g., insulin, antibodies). These systems are not intrinsically compatible as there are no free electrons in biology that could be transmitted to biological wires and control cell-based electronic circuits. Instead, biohybrid devices are envisioned that transmit information across this electron-molecule divide. New interfaces are needed that accept molecules from biology and create electrons for devices and the reverse. Such integrated systems designed and constructed within RE-BIONICS will be capable of this bidirectional communication for memory and computation. The project will build the components and information theory needed to construct biohybrid devices that could eventually be embedded within a biological system and provide electronic control. In addition to building capabilities for designing and constructing completely new biodevices, a most important aspect of this work is that it will bring together researchers and stakeholders from many disciplines, including biology, chemistry, materials science, and computer, electrical, chemical, and bioengineering. The project builds on the interdisciplinary nature of the project with Research Team from computer science, electrical engineering and bioengineering. The research thrusts span computer science and information theory, microelectromechanical systems, biofabrication and redox biology, and synthetic biology. Also, two interdisciplinary teams of undergraduate students from UMD and UNL will participate in the international Genetically Engineered Machine (iGEM) program and competition, and participate in specific outreach activities targeting Middle and High school students within the Future Problem Solving Program (FPSPI) at UNL. Further, this project will promote the participation of women, historically underrepresented in electrical engineering, representing more than majors in biology and bioengineering. RE-BIONICS researchers will also interact with federal agencies including NIST, FDA, and the Army Research Laboratory, gaining exposure to manufacturing and regulatory issues, as well as direct application areas such as national security. This project exploits reduction-oxidation (redox) mediators that are the biological equivalents of free electrons in electronics. The reactions represent packets of information transferred within biology. The project is organized into three specific aims. In Aim 1, the team will design, build and test device elements that facilitate information transfer from molecules of biological systems to electrons of microelectronic systems and the reverse. Using the principles of synthetic biology, bacterial cells will be engineered to recognize small signaling molecules, an example being pyocyanin that is secreted by opportunistic pathogen, Pseudomonas aeruginosa. Based on this recognition, these and other engineered sensing cells will produce -galactosidase, an enzyme that can be electrochemically quantified. In addition, cells will be engineered to accept electrons from devices and in a programmed manner, "turn on" gene expression that can modulate cell behavior. In Aim 2, the team will design and construct a biological read/write memory device, based on the biopolymer melanin, that can be accessed both biologically and electronically. In Aim 3, the team will integrate these elements creating biohybrid circuits, such as bioelectric logic gates, and biologic to electronic to biologic signaling systems, culminating in an electronically-controlled device that interprets molecular information, computes desired outcomes and electronically actuates cells to signal and control biological populations. There are three fundamentally novel aspects to this work. First, it will demonstrate the potential to transfer information from biological systems to microelectronic systems and the reverse, forming the basis for bioelectronic integrated computing systems. Second, it will demonstrate electronically-controlled synthesis of a novel, reliable and stable biological memory device. Third, it will develop a technological framework for the development of bio-hybrid computing devices that efficiently sense and process chemical information as well as operate within and control complex biological systems.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.

Re-Bionics项目（基于分子通信的氧化还原生物电子学）的目的是创建第一台生物电子设备，以介导生物学和电子学之间的快速且功能齐全的信息交换。这些设备将有可能改变医疗保健，从而实现电信监测和远程/自主药物输送，并促进农业和网络防御中的环境监测，而将生物学现象与电子学很重要。这项工作的技术基础认识到微电子设备取决于电子处理的电子处理，而生物学取决于分子（例如胰岛素，抗体）。这些系统在本质上不兼容，因为生物学中没有免费电子可以传输到生物线和基于控制细胞的电子电路。取而代之的是，设想生物杂交设备在该电子分子划分之间传输信息。需要新的接口，以接受生物学分子并为设备和反向创建电子。这种在重生学中设计和构建的集成系统将能够进行这种双向通信，以进行内存和计算。该项目将构建构建生物杂交设备所需的组件和信息理论，这些设备最终可以嵌入生物系统中并提供电子控制。除了构建设计和构建全新生物版本的功能外，这项工作的最重要方面还将召集许多学科的研究人员和利益相关者，包括生物学，化学，材料科学以及计算机，电脑，电气，化学和生物工程。 该项目基于该项目的跨学科性质与计算机科学，电气工程和生物工程的研究团队。该研究推动计算机科学和信息理论，微电力系统，生物制作和氧化还原生物学以及合成生物学。 此外，来自UMD和UNL的两个本科生的跨学科团队将参加国际基因工程机器（IGEM）计划和竞争，并参与UNL的未来中学学生（FPSPI）的特定外展活动。 此外，该项目将促进妇女的参与，历史上代表着电气工程的人数不足，而不是生物学和生物工程专业的专业。 重生研究人员还将与NIST，FDA和陆军研究实验室等联邦机构进行互动，获得制造和监管问题的风险以及国家安全等直接应用领域。该项目利用了电子等电子在电子中的生物等效物的还原氧化（氧化还原）介体。这些反应代表了在生物学中传递的信息包。 该项目分为三个特定目标。在AIM 1中，团队将设计，构建和测试设备元素，以促进信息从生物系统分子到微电子系统的电子和相反的信息。使用合成生物学的原理，将设计细菌细胞以识别小信号分子，一个例子是pyocyanin，由机会性病原体Pseudomonas aeruginosa分泌。基于这种识别，这些和其他工程的传感细胞将产生 - 半乳糖苷酶，半乳酶是一种可以通过电化学定量的酶。此外，将设计细胞以从设备中接受电子，并以编程的方式“打开”可以调节细胞行为的基因表达。在AIM 2中，该团队将根据生物聚合物黑色素设计和构建一个生物学读/写作记忆装置，可以从生物学和电子上访问。在AIM 3中，团队将整合这些元素，形成生物杂交电路，例如生物电路，以及电子通向生物学信号系统的生物学，并在电子控制的设备中达到顶点，以解释分子信息，以计算所需的量产，并计算出所需的细胞和电子对信号和控制生物的作用。 这项工作有三个根本新颖的方面。首先，它将证明将信息从生物系统转移到微电子系统和反向的潜力，从而构成了生物电子集成计算系统的基础。其次，它将证明一种新型，可靠和稳定的生物记忆装置的电子控制合成。第三，它将开发一个技术框架，用于开发生物混杂计算设备，该设备有效地感知和处理化学信息并在内部和控制复杂的生物系统内部运行。这项奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响来通过评估来支持的。

项目成果

Homologous Quorum Sensing Regulatory Circuit: A Dual-Input Genetic Controller for Modulating Quorum Sensing-Mediated Protein Expression in E. coli.

• DOI: 10.1021/acssynbio.0c00179
• 发表时间: 2020-10-16
• 期刊: ACS synthetic biology
• 影响因子: 4.7
• 作者: Hauk P;Stephens K;Virgile C;VanArsdale E;Pottash AE;Schardt JS;Jay SM;Sintim HO;Bentley WE
• 通讯作者: Bentley WE

Catechol Patterned Film Enables the Enzymatic Detection of Glucose with Cell Phone Imaging

• DOI: 10.1021/acssuschemeng.1c04896
• 发表时间: 2021-10
• 期刊: ACS Sustainable Chemistry & Engineering
• 影响因子: 8.4
• 作者: Si Wu;J. Rzasa;Eunkyoung Kim;Zhiling Zhao;Jinyang Li;W. Bentley;N. N. Payne-N.;Xiaowen Shi;G. Payne

A redox-based electrogenetic CRISPR system to connect with and control biological information networks

• DOI: 10.1038/s41467-020-16249-x
• 发表时间: 2020-05-15
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Bhokisham, Narendranath;VanArsdale, Eric;Bentley, William E.
• 通讯作者: Bentley, William E.

Hydrogel Patterning with Catechol Enables Networked Electron Flow

• DOI: 10.1002/adfm.202007709
• 发表时间: 2021-01
• 期刊: Advanced Functional Materials
• 影响因子: 19
• 作者: Si Wu;Zhiling Zhao;J. Rzasa;Eunkyoung Kim;Jinyang Li;Eric VanArsdale;W. Bentley;Xiaowen Shi;G. Payne

Transglutaminase-mediated assembly of multi-enzyme pathway onto TMV brush surfaces for synthesis of bacterial autoinducer-2

• DOI: 10.1088/1758-5090/ab9e7a
• 发表时间: 2020-10-01
• 期刊: BIOFABRICATION
• 影响因子: 9
• 作者: Bhokisham, Narendranath;Liu, Yi;Bentley, William E.
• 通讯作者: Bentley, William E.