Remote-Control Mechano-Genetics and Epigenetics for Live Cell Manipulation

用于活细胞操作的远程控制机械遗传学和表观遗传学

• 批准号: 9765353
• 负责人: Yingxiao Wang
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765353
• 关键词: Biochemical; Biological; Biological Process; Biological Sciences; Biology; Biosensing Techniques; Biosensor; Calcium Signaling; Cell physiology; Cells; Communities; Coupled; Development; Dreams; Engineering; Epigenetic Process; Event; Feedback; Fluorescence Resonance Energy Transfer; Gene Activation; Gene Expression; Genes; Genetic; Genetic Engineering; Genetic Programming; Genetic Transduction; Genomics; Guide RNA; Imagery; Lead; Mechanics; Medical; Membrane; Methods; Microbubbles; Molecular; One-Step dentin bonding system; Optics; Organism; Output; Proteins; Reading; Regulation; Reporter Genes; Resolution; Science; Signal Transduction; Technology; Therapeutic; Time; Tissues; Transcription Coactivator; Ultrasonic Transducer; Ultrasonic wave; Ultrasonics; Ultrasonography; base; biomedical scientist; cellular engineering; clinical application; design; digital; engineered T cells; epigenetic regulation; experience; live cell imaging; mechanical force; meter; nuclease; optogenetics; pressure; prototype; remote control; sensor; spatiotemporal; tool; tumor

Remote-Control Mechano-Genetics and Epigenetics for Live Cell Manipulation It has been a long held dream for biomedical scientists to dynamically and precisely manipulate molecular activities and cellular functions in distance. Our project aims to bring this dream one step closer to reality, by engineering cellular mechano-sensors to convert the remote ultrasonic signal into intracellular molecular signals, and by engineering genetic transduction modules (GTMs) to relay the molecular signals into dynamically and precisely controlled genetic and epigenetic signals. This remote-controlled mechano- genetics/epigenetics (ReCoM) technology should allow the live cell engineering and manipulation with high spatiotemporal resolution. Our team has ample experience in ultrasound, biosensing, live cell imaging, and molecular and cellular engineering technologies. We have already engineered a prototype ultrasound- activatable cell. Here we propose to systematically develop and optimize the modularized ReCoM technology in three steps: (1) Optimize mechano-sensors that can receive ultrasonic signals via micro-bubbles and convert them into intracellular biochemical signals; (2) Engineer GTMs to relay these specific molecular signals to genetic outputs; (3) Encode the GTMs with locus-specific genetic and epigenetic modulators to allow the remote, dynamic, and precise control of cellular function and fate. This approach should allow the remote-controlled genetic and epigenetic activation in live cells with a high spatiotemporal precision in a non- invasive manner for therapeutic applications. The method should also provide a general approach to dynamically control molecular and cellular functions for biological studies and clinical applications.

活细胞操纵的遥控机制遗传学和表观遗传学 动态、精确地操控分子一直是生物医学科学家的梦想 远距离的活动和细胞功能。我们的项目旨在通过以下方式使这一梦想更接近现实 工程化细胞力学传感器将遥测超声信号转化为细胞内分子 信号，并通过工程基因转导模块(GTM)将分子信号传递到 动态和精确地控制遗传和表观遗传信号。这个遥控机械- 遗传学/表观遗传学(RECOM)技术应该允许高水平的活细胞工程和操纵 时空分辨率。我们的团队在超声波、生物传感、活细胞成像和 分子和细胞工程技术。我们已经设计了一个超声波原型- 可激活的细胞。在这里，我们提出了系统地开发和优化模块化的RECOM技术 分三个步骤：(1)优化机械传感器，通过微气泡和 将它们转化为细胞内生化信号；(2)设计GTMS以传递这些特定的分子 信号到遗传输出；(3)用基因座特异的遗传和表观遗传调节子编码GTMS，以 实现对蜂窝功能和命运的远程、动态和精确控制。这种方法应该允许 远程控制活细胞中的遗传和表观遗传激活，在非 用于治疗应用的侵入性方式。该方法还应提供一种通用的方法来 动态控制分子和细胞功能，用于生物学研究和临床应用。