Collaborative Research: Elucidating the Mechanism of Magnetogenetics for Remote Activation of Cell Function

合作研究：阐明磁遗传学远程激活细胞功能的机制

• 批准号: 1930163
• 负责人: Jonathan Dordick
• 金额: $ 30万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1930163&HistoricalAwards=false
• 关键词: Collaborative; Research; Elucidating; Mechanism; Magnetogenetics

We are entering a new age of manufacturing where living cells are used to produce fuels, chemicals, and therapeutic proteins. Cell therapies offer the promise of enhancing a patient's natural immune system cells to fight cancer and other metabolic diseases. These technologies are possible because of our ability to control the metabolism of cells. Most of the currently used control methods rely on chemical signaling, but chemical signals can also interfere with normal cell metabolism. This project will develop a alternate biological control system that responds to magnetic signals. Research opportunities for undergraduates will develop a skilled STEM workforce. Outreach efforts will be multiplied through development of an 8-week summer workshop for K-12 teachers and high school students. Remote gene activation through static and alternating/oscillating magnetic fields will be evaluated for the control of protein expression in mammalian cells and cell cultures. The core hypothesis to be tested is that magnetic fields can induce the opening of ion channels upon co-expression of and mediation by ferritin tethered to the ion channel. The ferritin nanoparticles would serve as transducers, converting magnetic signals into physical ones that can activate a signal cascade. Magnetic fields offer much finer temporal and spatial control than is available using chemical signaling. The scope of the project and specific activities are threefold. First, elucidate the mechanism of static and oscillating/alternating magnetic field induced activation of ion channels. Second, tune sensitivity and responsiveness of magnetically activated ion channels by constructing genetic systems and controlling cell culture conditions to enhance ferritin properties leading to transient receptor potential (TRP) channel gating. Third, as a bioengineering application, use the genetically-encoded TRP channel-ferritin system to remotely control gene transcription and induce expression of key proteins involved in neurogenesis. The outcome of this study could be a foundation for designing methods to control cellular signaling, gene transcription, and protein expression/production for biomanufacturing applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

我们正在进入一个新的制造时代，其中活细胞用于生产燃料，化学物质和治疗蛋白。细胞疗法提供了增强患者天然免疫系统细胞以抵抗癌症和其他代谢疾病的承诺。 由于我们控制细胞的代谢能力，因此这些技术之所以可能。当前使用的大多数控制方法依赖化学信号传导，但是化学信号也会干扰正常的细胞代谢。 该项目将开发出响应磁信号的替代生物控制系统。本科生的研究机会将发展熟练的STEM劳动力。通过为K-12老师和高中生开发为期8周的夏季研讨会，将进行外展工作。通过静态和交流/振荡磁场的远程基因激活将评估哺乳动物细胞和细胞培养物中蛋白质表达的控制。要测试的核心假设是，磁场可以在铁蛋白束缚在离子通道的同时表达和介导后诱导离子通道的打开。铁蛋白纳米颗粒将用作传感器，将磁信号转换为可以激活信号级联的物理信号。磁场提供的时间和空间控制比使用化学信号传导可用。项目范围和特定活动的范围是三倍。首先，阐明静态和振荡/交替磁场引起的离子通道激活的机理。其次，通过构建遗传系统和控制细胞培养条件来增强铁蛋白特性，从而增强了瞬时受体电位（TRP）通道门控，磁性激活的离子通道的敏感性和反应性。第三，作为一种生物工程应用，使用遗传编码的TRP通道 - 铁蛋白系统来远程控制基因转录，并​​诱导与神经发生有关的关键蛋白的表达。这项研究的结果可能是设计方法来控制生物制造应用的细胞信号传导，基因转录和蛋白质表达/产生方法的基础。该奖项反映了NSF的法定任务，并被认为值得通过基金会的智力优点和更广泛的影响标准通过评估来进行评估。