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

项目摘要/摘要 分子生物学的技术进步导致了各种创新工具的开发，以 控制基因表达。这些工具对于审问复杂的生物学问题和 开发下一代疗法。然而，仍有两个主要挑战有待解决。 一种是远程控制按需转录，具有最高的时间和空间分辨率。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的遗传工具来更好地控制基因 单元格内的表达式。这一新工具的基础是重新布线蜂窝网络并将能量转换为 生物作用。我们打算利用电磁和生物光子学的力量来控制基因。 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，即 可以通过电磁场(EMF)远程控制。这种独特的人造细胞机器将使用 激活特定转录因子进而开启基因的生物光子学原理 以最高的精确度转录。 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，它可以将电动势转换为 光子。同时，在第二个目标中，我们将开发一个与 生物磁性开关和控制转录，而不与任何内源信号通路相互作用。 最后，在第三个目标中，我们将在体内测试合成电路，在相关的动物模型中。 这种磁光电路将绕过目前化学、光学和磁学方法的限制。 通过允许基因定向、非侵入性远程控制基因表达， 生理上相关的时间方式。我们预计，在完成拟议的研究后，我们将 创造一种创新的工具，这将对基础研究、药物开发和开发大有裨益 下一代以合成生物学为基础的疗法。

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.