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: 10670969
• 负责人: Cheemeng Tan
• 金额: $ 38.1万
• 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/10670969
• 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 解剖杂种细菌材料微电位的非生长活性状态 最近的工作一直对工程统一细菌感兴趣，以解决各种生物医学 挑战，例如特定药物输送，使用CRISPR-CA的基因编辑以及连续合成药物 在疾病部位。与非生存设备相反，细菌可以满足这些未满足的需求，因为它们 已经生活在人体和疾病部位，积极朝着刺激，检测和反应 刺激，并连续合成药物。但是，一个重大的挑战是防止不受控制 细菌的扩散，同时保持其活跃功能。为了应对挑战，社区必须 拥有一项万无一失的安全措施，可防止在任何情况下复制治疗细菌。这 测量将确保细菌无法在患者和大生态系统中复制。没有复制， 突变也很少见，突变体不能扩散。此外，可以将非复制实体施加更多 与自动复制实体相比。然而，到目前为止，也试图停止细菌复制 损害细菌的治疗活性。为了解决这个关键的瓶颈，我的实验室创建了细菌 这不能生长，但是通过将合成材料与细菌整合在一起来保持高代谢。非成长 但是活跃的细菌继续合成蛋白质，移动并应对化学刺激。我的研究会 进一步研究了细菌的非生长但活性状态的潜在机制。 然后，新的理解将用于提高和启用非成长但活性的特定特征 细菌与未来的生物医学应用有关。我将利用我先前关于合成基因的工作 表达，细菌信息处理和CRISPR-DCAS9分子工具。这项工作将揭示新的 材料蛋白范式抑制生长但保留活细胞活性。此外，这项工作 将实现用于广泛的生物医学应用的优质，安全和活跃的杂种材料微电位。