Semi-synthetic, magneto-photonic circuit for non-invasive control of cellular function

用于非侵入性控制细胞功能的半合成磁光子电路

• 批准号: 10277517
• 负责人: Assaf A Gilad
• 金额: $ 202.66万
• 依托单位: CENTRAL MICHIGAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2024-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10277517
• 关键词: Address; Animal Model; Basic Science; Binding; Biological; Bioluminescence; Biophotonics; Catfish; Cell Survival; Cell physiology; Cells; Chemicals; Chimeric Proteins; Complex; Data; Development; Disease; Electromagnetic Fields; Electromagnetics; Enzymes; Gene Expression; Gene Order; Gene Proteins; Genes; Genetic; Genetic Transcription; Glass; Goals; Heterodimerization; Homodimerization; Implant; In Vitro; Intervention; Libraries; Light; Luciferases; Magnetism; Mammalian Cell; Molecular Biology; Mus; Mutagenesis; Operative Surgical Procedures; Optics; Outcome; Photobleaching; Photons; Phototoxicity; Physiological; Proteins; Public Health; Regulation; Reporter; Research; Resolution; Rodent; Signal Pathway; System; Technology; Testing; Therapeutic; Tissues; Transcriptional Regulation; absorption; base; blood glucose regulation; clinical application; design; dimer; drug development; human disease; in vivo; innovation; light intensity; light scattering; luciferin; millisecond; next generation; novel; novel therapeutics; optical fiber; optogenetics; photonics; promoter; reconstitution; remote control; screening; synthetic biology; therapeutic gene; tool; transcription factor; transmission process

PROJECT SUMMARY/ABSTRACT Technological advances in molecular biology have led to the development of a variety of innovative tools to control gene expression. Those tools are crucial for both interrogating complex biological questions and developing the next generation of therapeutics. Yet, there are two main challenges that remain to be resolved. One is remote controlling of transcription on demand with the utmost temporal and spatial resolution. The other is to avoid crosstalk with existing signaling pathways. In this study, we propose to develop a new genetic tool based on synthetic biology to better control gene expression within cells. This novel tool is based on rewiring cellular networks and converting energy into biological action. We intend to harness the power of electromagnetism and biophotonics to control gene expression. Our goal is to devise multiplex gene arrangements, fusion proteins and transcription factors, that can be controlled remotely by electromagnetic fields (EMF). This unique, artificial cellular machinery will use biophotonic principles for activation of specific transcription factors and subsequently switch on gene transcription with the utmost precision. In the first Aim we will develop and evolve a genetically encoded biomagnetic switch that can convert EMF to photons. In parallel, in the second Aim we will develop an orthogonal transcription machinery that interacts with the biomagnetic switch and controls transcription without interacting with any endogenous signaling pathway. Finally, in the third Aim we will test the synthetic circuit in vivo, in a relevant animal model. This magneto-photonic circuit will by-pass the limitations of current chemical, optical, and magnetic approaches by allowing genetically targeted, non-invasive remote control of gene expression in a highly precise and physiologically relevant temporal manner. We anticipate that upon completion of the proposed research we will create an innovative tool that will be immensely beneficial for basic research, drug development and developing the next generation of synthetic biology-based therapeutics.

项目概要/摘要 分子生物学的技术进步导致了各种创新工具的开发 控制基因表达。这些工具对于询问复杂的生物学问题和 开发下一代疗法。然而，还有两个主要挑战有待解决。 一是以最大的时间和空间分辨率远程控制转录。另一个 是为了避免与现有信号通路的串扰。 在这项研究中，我们建议开发一种基于合成生物学的新遗传工具，以更好地控制基因 细胞内表达。这种新颖的工具基于重新布线蜂窝网络并将能量转换为 生物作用。我们打算利用电磁学和生物光子学的力量来控制基因 表达。我们的目标是设计多重基因排列、融合蛋白和转录因子， 可以通过电磁场（EMF）进行远程控制。这种独特的人造细胞机器将使用 激活特定转录因子并随后打开基因的生物光子原理 以最精确的方式进行转录。 在第一个目标中，我们将开发和进化一种基因编码的生物磁开关，可以将 EMF 转换为 光子。与此同时，在第二个目标中，我们将开发一种正交转录机制，与 生物磁开关并控制转录，而不与任何内源信号通路相互作用。 最后，在第三个目标中，我们将在相关动物模型中测试体内合成电路。 这种磁光子电路将绕过当前化学、光学和磁方法的局限性 通过允许以高度精确和精确的方式对基因表达进行基因靶向、非侵入性远程控制 生理相关的时间方式。我们预计，在完成拟议的研究后，我们将 创建一个对基础研究、药物开发和开发将非常有益的创新工具 下一代基于合成生物学的疗法。