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

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发展， 控制基因表达。这些工具对于询问复杂的生物学问题和 开发下一代的治疗方法然而，仍有两个主要挑战有待解决。 一个是远程控制转录的需求与最大的时间和空间分辨率。另 是为了避免与现有信号通路的串扰。 在这项研究中，我们提出开发一种新的基于合成生物学的遗传工具，以更好地控制基因 在细胞内表达。这种新工具是基于重新布线蜂窝网络和转换成能量 生物作用。我们打算利用电磁和生物光子的力量来控制基因 表情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 用于激活特定转录因子并随后开启基因的生物光子原理 以最高的精度转录。 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 光子同时，在第二个目标中，我们将开发一种正交转录机制， 生物磁性开关和控制转录，而不与任何内源性信号传导途径相互作用。 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。 这种磁光电路将绕过目前的化学，光学和磁性方法的限制 通过允许基因靶向的、非侵入性的远程控制基因表达， 生理相关的时间方式。我们预计，在完成拟议的研究后， 创造一个创新的工具，这将是非常有益的基础研究，药物开发和开发 下一代基于合成生物学的治疗方法

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.