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

项目摘要 混合细菌材料微器件不生长但活性状态的剖析 最近的工作是通过工程共生细菌来解决各种生物医学问题 挑战，例如特定的药物输送、使用CRISPR-Cas的基因编辑和药物的连续合成 在疾病现场。与非生物设备不同，细菌可以满足这些未得到满足的需求，因为它们 已经生活在人体和疾病部位，积极地向刺激移动，检测和响应 刺激，并不断合成药物。然而，一个重大的挑战是防止失控的 细菌的增殖，同时保持其活跃的功能。为了应对这一挑战，社会必须 采取万无一失的安全措施，防止治疗性细菌在任何情况下复制。这 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， 突变也很罕见，突变不会传播。此外，非复制实体可以被给予更多的剂量 而不是一个自动复制的实体。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起来保持高度新陈代谢。不再增长的- 但活性细菌继续合成蛋白质，移动，并对化学刺激做出反应。我的研究将 进一步研究控制细菌不生长但活跃状态的潜在机制。 然后，新的理解将被用来促进和启用不增长但活跃的 与未来生物医学应用相关的细菌。我将利用我之前在合成基因方面的工作。 表达、细菌信息处理和CRISPR-dCas9分子工具。这项工作将揭示一种新的 抑制生长但保持活细胞活性的物质-蛋白质范式。此外，这项工作 将为广泛的生物医学应用提供一种卓越、安全和活性的混合细菌材料微设备。

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.