Dissecting the non-growing-but-active state of a hybrid bacteria-material microdevice

剖析混合细菌材料微器件的非生长但活跃状态

• 批准号: 10797951
• 负责人: Cheemeng Tan
• 金额: $ 24.98万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797951
• 关键词: Address; Bacteria; Cells; Chemicals; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Devices; Disease; Dose; Drug Delivery Systems; Ecosystem; Engineering; Ensure; Future; Gene Expression; Genes; Growth; Human body; Hybrids; Measures; Metabolism; Molecular; Mutation; Patients; Proliferating; Protein Biosynthesis; Proteins; Research; Safety; Site; Stimulus; Synthetic Genes; Therapeutic; Work; commensal bacteria; drug synthesis; information processing; interest; microdevice; mutant; preservation; prevent; therapeutically effective; tool

PROJECT ABSTRACT Dissecting the non-growing-but-active state of a hybrid bacteria-material microdevice Recent work has been interested in engineering commensal bacteria to address various biomedical challenges, such as specific drug delivery, gene-editing using CRISPR-Cas, and continuous synthesis of drugs at disease sites. In contrast to non-living devices, bacteria can address these unmet needs because they already live in the human body and at disease sites, move actively towards stimuli, detect and respond to stimuli, and synthesize drugs continuously. However, a significant challenge is to prevent the uncontrolled proliferation of bacteria, while keeping their active functions. To address the challenge, the community must have a foolproof safety measure that prevents the replication of therapeutic bacteria in any condition. This measure will ensure that the bacteria cannot replicate in patients and the large ecosystem. Without replication, mutation is also rare, and mutants cannot spread. Furthermore, a non-replicating entity can be dosed more precisely than an auto-replicating entity. Thus far, however, attempts to stop bacterial replication also compromise the therapeutic activity of bacteria. To address this critical bottleneck, my lab has created bacteria that cannot grow but keep high metabolism by integrating synthetic materials with bacteria. The non-growing- but-active bacteria continue to synthesize proteins, move, and respond to chemical stimuli. My research will further investigate the underlying mechanisms that govern the non-growing-but-active state of the bacteria. The new understanding will then be used to boost and enable specific features of the non-growing-but-active bacteria relevant for future biomedical applications. I will leverage my prior work about synthetic gene expression, bacterial information processing, and CRISPR-dCas9 molecular tools. The work will reveal a new material-protein paradigm for inhibiting growth but preserving the activity of living cells. Furthermore, the work will enable a superior, safe, and active hybrid bacteria-material microdevice for broad biomedical applications.

项目摘要 混合细菌-材料微器件的非生长但活性状态剖析 最近的工作一直对工程化肠道细菌以解决各种生物医学问题感兴趣。 挑战，如特定的药物输送，使用CRISPR-Cas进行基因编辑，以及药物的连续合成 在疾病现场。与非生命设备相比，细菌可以解决这些未满足的需求，因为它们 已经生活在人体和疾病部位，积极地向刺激物移动，检测和响应 刺激，并不断合成药物。然而，一个重大挑战是防止不受控制的 细菌增殖，同时保持其活跃功能。为了应对挑战，社会必须 有一个万无一失的安全措施，防止在任何条件下的治疗细菌的复制。这 这一措施将确保细菌不能在患者和大型生态系统中复制。如果没有复制， 突变也是罕见的，突变体不能传播。此外，非复制实体可以被给予更多剂量。 比一个自动复制的实体更精确。然而，到目前为止，阻止细菌复制的尝试也 损害细菌的治疗活性。为了解决这一关键瓶颈，我的实验室创造了细菌 它不能生长，但通过将合成材料与细菌结合来保持高代谢。不生长- 但活跃的细菌继续合成蛋白质，移动，并对化学刺激作出反应。我的研究将 进一步研究控制细菌非生长但活跃状态的潜在机制。 新的理解将被用来促进和实现非增长但活跃的特定功能， 与未来生物医学应用相关的细菌。我将利用我之前关于合成基因的研究成果 表达，细菌信息处理和CRISPR-dCas 9分子工具。这项工作将揭示一个新的 材料-蛋白质范例，用于抑制生长但保持活细胞的活性。此外，工作 将使上级的，安全的，和积极的混合细菌材料的微器件广泛的生物医学应用。

项目成果

Microfluidic Printing-Based Method for the Multifactorial Study of Cell-Free Protein Networks.

• DOI: 10.1021/acs.analchem.2c01851
• 发表时间: 2022-08-09
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Zhou, Chuqing;Shim, Jiyoung;Fang, Zecong;Meyer, Conary;Gong, Ting;Wong, Matthew;Tan, Cheemeng;Pan, Tingrui
• 通讯作者: Pan, Tingrui