SemiSynBio-III: Towards Understanding and Controlling Redox for Microbial Memory and INteractions - TURIN

现代电子技术改变了我们的生活，它允许信息通过电磁辐射进行通信，并通过集成电路进行处理。 这种电子设备可以快速、廉价和无差错地传输、接收和处理数字信息。 生物学也擅长信息处理，通常通过各种方式进行交流（例如，电的、机械的和分子的），以及通过通常嵌入多细胞系统中的基于细胞的“微处理器”进行处理（即，组织或聚生体）。 这样的生物系统可以处理噪声信息，以学习、适应和存储信息供后代使用。 这项研究的长期愿景是融合电子学和生物学中的正交信息处理能力。这被称为“生物电子通信”，该团队正在开发一种促进这种变革能力的新方法。他们的方法利用了电子流，并且它桥接了存在于生物设备界面处的差距-电子在微电子中自由流动，但在网络化氧化和还原中转移（即，氧化还原）反应。通过开发与氧化还原相关的合成生物学，使电子能够转移到“智能”材料，而这些材料又是电活性组件微电子设备，该团队已经为开辟新的生物电子通信线路奠定了基础。他们工作的一个独特之处是使用电子技术刺激基因表达，并将可检索的“编码”信息“写入”微生物基因组。为这些能力设想了许多机会。例如，通过构建“生物混合”设备来实现这些功能，人们可以窃听和控制我们的免疫系统，因为它们对抗感染并指导伤口愈合。这些过程依赖于氧化还原通讯。人们可能能够探索胃肠道或根际中的分子通讯，其中基于氧化还原的信号传导也很普遍。解开这些系统的复杂性将有助于应对人类健康、环境安全以及粮食生产和作物保护的挑战。都灵多学科团队不仅准备好开发生物电子通信的基础，而且通过与行业和政府机构的广泛合作网络（即，NIST，FDA）。重要的是，这些努力将包括在工程、计算机科学和生物学的交叉领域培训本科生和研究生，以及开发一个新的基于氧化还原的生物电子学暑期学校。该项目的长期愿景是融合电子学和生物学的正交信息处理能力，以开发基于氧化还原的生物电子学新兴领域。这项研究的首要假设是，氧化还原模态提供了前所未有的生物学和电子学接口的能力，因为：（i）电化学提供了对这种模态的电子访问（即，氧化还原信号可以容易地在电极上产生和检测）;和（ii）氧化还原是细胞与其环境交换信息的天然生物学形态。该项目在四个技术重点（TF）领域提供了几个重要的智力贡献。第一个TF将制造生物相容性材料（即，薄的水凝胶膜）作为电子层，其将氧化还原和电信号相互转换。这些将把电极施加的输入转换为生物识别的氧化还原信号（例如，H2 O2，吩嗪类）。 第二个TF将产生能够相互转换来自氧化还原模态和天然生物信号传导模态（群体感应自诱导物）的信号的通信细胞，以实现与更广泛的微生物群体的通信。 第三个TF将创建决策细胞，这些细胞可以通过电输入来指示观察它们的上下文并执行上下文相关的布尔逻辑操作：要么写入它们的基因组（永久记忆），要么调整聚生体种群（我们假设种群设定点是动态记忆的一种很难理解的形式）。 第四个TF将使用系统级建模来整合研究活动，以通过电组装生物电子网络建立能量和信息有效流动的指标。通过物理和计算连接这些TF区域的组件，生物混合装置被设想为打开生物和非生物世界之间的通信线路。此外，PI将启动一个新的暑期学校，以氧化还原为基础的生物电子学和系统以及合成生物学为基础的设计，特别是针对本地本科生和研究生，包括来自其他少数民族服务机构的学生。暑期学校将在这三所院校之间轮换，并利用各自的专业知识和马里兰州的机构优势（科学和工程少数民族中心），GT和威斯康星州（WID照明发现中心），以确保多样化的参与和量化的成果。该项目由生物科学局（BIO）分子和细胞生物科学处（MCB）联合资助，计算机和信息科学与工程局（CISE）的计算和通信基础司（CCF），工程局（ENG）的电气、通信和网络系统司（ECCS），以及数学和物理科学理事会（MPS）的材料研究部（DMR）该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Modern electronics transformed our lives by allowing information to be communicated through electromagnetic radiation and processed through integrated circuits. Such electronic devices can transmit, receive and process digital information rapidly, cheaply and without error. Biology is also expert at information processing, typically communicating through various modalities (e.g., electrical, mechanical and molecular), and processing through cell-based “micro-processors” that are often embedded within multicellular systems (i.e., tissue or consortia). Such biological systems can process noisy information to learn, adapt and store information for use by future generations. The long-term vision of this research is the fusion of orthogonal information processing capabilities in electronics and biology. This is denoted “bioelectronic communication” and the team is developing a new way of facilitating this transformative capability. Their approach exploits electron flow and it bridges the gap that exists at the bio-device interface - electrons flow freely in microelectronics but are transferred in networked oxidation and reduction (i.e., redox) reactions in biology. By developing redox-linked synthetic biology that enables electron transfer to and from “smart” materials that, in turn, are electroactive components microelectronic devices, the team has already built the basis for opening new lines of bioelectronic communication. A unique feature of their work will be the use of electronics to stimulate gene expression as well as to “write” retrievable “coded” information onto the genome of microbes. There are many opportunities envisioned for these capabilities. For example, with “biohybrid” devices built to enable these capabilities, one may be able to eavesdrop on and control our immune systems as they combat infections and guide wound healing. These processes rely on redox communication. One may be able to explore the molecular communication in the GI tract or in the rhizosphere, where redox based signaling is also prevalent. Unraveling the complexities of these systems will help address the challenges of human health, environmental security, as well as food production and crop protection. The TURIN multidisciplinary team is well-poised to not only develop the fundamental basis for bioelectronic communication, but to catalyze its transformation into practice through an extensive network of collaborations with industry and governmental agencies (i.e., NIST, FDA). Importantly, efforts will include the training of undergraduate and graduate students at the intersection of engineering, computer science and biology, and the development of a new summer school on redox-based bioelectronics. The projects’s long-term vision is the fusion of orthogonal information processing capabilities of electronics and biology for the development of an emerging field of redox-based bioelectronics. The overarching hypothesis of this research is that the redox modality provides an unprecedented ability to interface biology and electronics because: (i) electrochemistry provides electronic access to this modality (i.e., redox signals can be readily generated and detected at an electrode); and (ii) redox is a native biological modality by which cells exchange information with their environment. The project offers several important intellectual contributions across four Technological Focus (TF) areas. The first TF will fabricate biocompatible materials (i.e., thin hydrogel films) as an electronic layer that interconverts redox and electrical signals. These will transduce electrode-imposed inputs into biologically-recognized redox signals (e.g., H2O2, phenazines). The second TF will create communicating cells capable of interconverting signals from the redox modality and a native biological signaling modality (quorum sensing autoinducers) to enable communication to a broader microbial population. The third TF will create decision-making cells that can be instructed by electric inputs to observe their context and perform context-dependent Boolean logic operations: either to write to their genome (permanent memory) or to adjust consortium populations (we hypothesize that population setpoints are a poorly-understood form of dynamic memory). The fourth TF will integrate research activities using systems-level modeling to establish metrics for the efficient flow of energy and information through an electroassembled bio-electronic network. By physically and computationally linking the components of these TF areas, biohybrid devices are envisioned that open lines of communication between the biotic and abiotic worlds. Further, the PIs will initiate a new summer school on redox-based bioelectronics and systems and synthetic biology-based design, especially targeting local undergraduate and graduate students, including those from other minority serving institutions. Summer schools will rotate among the three institutions and leverage the respective PIs' expertise and institutional strengths at Maryland (Center for Minorities in Science and Engineering), GT, and Wisconsin (WID Illuminating Discovery Hub) to ensure diverse participation and quantified outcomes.This project has been jointly funded by Division of Molecular and Cellular Biosciences (MCB) in the Directorate for Biological Sciences (BIO), Division of Computing and Communication Foundations (CCF) in the Directorate for Computer and Information Science and Engineering (CISE), Division of Electrical, Communications and Cyber Systems (ECCS) in the Directorate for Engineering (ENG), and the Division of Materials Research (DMR) in the Directorate for Mathematical and Physical Sciences (MPS).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.