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.

实时细胞操纵的遥控机械基因和表观遗传学 生物医学科学家动态和精确操纵分子一直是一个长期以来的梦想 距离的活动和细胞功能。我们的项目旨在使这个梦想更接近现实， 工程细胞机械传感器，将远程超声信号转换为细胞内分子 信号，通过工程遗传转导模块（GTM）将分子信号传递到 动态和精确控制的遗传和表观遗传信号。这个遥控机械 - 遗传学/表观遗传学（OCOM）技术应允许实时细胞工程和操纵高 时空分辨率。我们的团队在超声，生物传感，实时细胞成像和 分子和细胞工程技术。我们已经设计了原型超声波 可激活的单元。在这里，我们建议系统地开发和优化模块化的OBOM技术 在三个步骤中：（1）优化可以通过微气泡接收超声信号的机械传感器 将它们转换为细胞内生化信号； （2）工程师GTMS以中继这些特定分子 遗传输出的信号； （3）用特异性遗传和表观遗传调节剂对GTM进行编码 允许远程，动态和精确控制细胞功能和命运。这种方法应允许 在非 - 非时空精度的活细胞中，远程控制的遗传和表观遗传激活 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 动态控制生物学研究和临床应用的分子和细胞功能。