Bioengineering a novel electromagnetic perspective gene as a tool for wireless control of excitable cells

生物工程新型电磁透视基因作为无线控制可兴奋细胞的工具

• 批准号: 10200903
• 负责人: Assaf A Gilad
• 金额: $ 51.49万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200903
• 关键词: Basic Science; Bioinformatics; Biologic Development; Biological; Biological Pacemakers; Biomedical Engineering; Biosensor; Brain; Brain region; Calcium; Cardiac; Cardiac pacemaker; Catfish; Cell membrane; Cell physiology; Cells; Chemicals; Clinic; Cloning; Complement; Complex; Contralateral; Deep Brain Stimulation; Development; Discipline; Disease; Effectiveness; Electrodes; Electromagnetic Fields; Electromagnetics; Electronics; Electrophysiology (science); Engineering; Forelimb; Future; Gene Activation; Genes; Genetic Crossing Over; Genetic Engineering; Glass; Goals; Growth; Health Sciences; Heating; Human; Image; Immunohistochemistry; Implant; Ion Channel; Kinetics; Lead; Light; Limb structure; Magnetism; Mammalian Cell; Membrane; Membrane Proteins; Methodology; Methods; Microelectrodes; Modern Medicine; Molecular; Molecular Biology; Motor; Motor Cortex; Motor Evoked Potentials; Motor output; Nature; Neuromodulator; Neurons; Neurosciences; Oocytes; Organism; Pharmaceutical Preparations; Population; Power Sources; Proteins; Rattus; Skeletal Muscle; Slice; Smooth Muscle; Specificity; Structure; Technology; Temperature; Testing; Tissues; Ultrasonography; Wireless Technology; Work; Xenopus laevis; associated symptom; base; bioinformatics tool; cDNA Library; design; effectiveness testing; electronic pacemaker; excitatory neuron; expression cloning; improved; in vivo; infancy; inhibitory neuron; motor control; neural circuit; neuronal excitability; neuroregulation; new technology; noninvasive brain stimulation; novel; promoter; receptor; reduce symptoms; remote control; response; sensor; side effect; skills; synthetic biology; technology development; tool; transmission process

Abstract: The ability to manipulate neuronal function in the living brain has a major impact both on human health and basic sciences. In the past half century, neuronal modulation via implantable microelectrodes in specific brain regions has been used to relief symptoms associated with a variety of neuronal disorders. However, this approach suffers from the need to implant complex, large and expansive electronic devices that depend on an external power supply, and the unexpected and undesirable side effects that the actual placement of the neurostimulation electrodes often produces. Recently, major advances in molecular and synthetic biology facilitated the cloning and optimization of receptors and channels that allow modulation of neuronal function in response to light, chemicals or temperature. However, the control of these proteins requires invasive delivery of the activator. Therefore, a non-invasive, remote controlled neuromodulator that can manipulate specific neuronal population in a non-invasive manner is an unmet need. To embark upon this challenge, we have investigated the potential of an alternative and novel method to remotely control cellular function through the transmission of non-invasive, electromagnetic fields (EMF). Using expression cloning, we have identified and cloned a single gene that encodes to a protein that responds to EMF. This unique gene has never been characterized before and was termed electromagnetic perceptive gene (EPG). EPG was cloned and expressed in mammalian cells, neuronal cultures and in rat’s brain. Immunohistochemistry showed that the expression of EPG is confined to the mammalian cell membrane, and that it can be expressed in a specific population, and in specific brain regions of the rat. Calcium imaging in mammalian cells and cultured neurons expressing EPG demonstrated that remote activation by EMF significantly increases intracellular calcium concentrations, indicative of cellular excitability. Moreover, wireless magnetic activation of EPG in rat motor cortex induced motor evoked responses of the contralateral forelimb in vivo. We hypothesize that the EPG technology will enable wireless control of neuronal function with cell, region and temporal specificity. Here we propose to thoroughly characterize the EPG in the cellular, molecular and functional levels. We will also test the effectiveness of the EPG technology to wirelessly control neuronal function in vivo. We anticipate that this new technology would transform the future of neuromodulation, complement existing neuromodulation tools, and considerably contribute to the understanding of complex neural circuits.

抽象的： 操纵活体大脑中神经元功能的能力对以下方面都有重大影响： 人类健康和基础科学。在过去的半个世纪中，通过植入式神经元调节 特定大脑区域的微电极已被用于缓解与某种疾病相关的症状 各种神经元疾病。然而，这种方法需要植入复杂的、 依赖于外部电源的大型且扩展的电子设备，以及 神经刺激的实际放置会产生意想不到的和不良的副作用 电极经常产生。最近，分子和合成生物学的重大进展 促进受体和通道的克隆和优化，从而调节 神经元对光、化学物质或温度做出反应的功能。然而，对这些的控制 蛋白质需要激活剂的侵入性递送。因此，一种非侵入式、远程控制的 能够以非侵入性方式操纵特定神经元群的神经调节剂是一种 未满足的需求。 为了应对这一挑战，我们研究了替代方案的潜力， 通过非侵入性传输来远程控制细胞功能的新方法， 电磁场（EMF）。使用表达克隆，我们已经鉴定并克隆了一个 编码对 EMF 做出反应的蛋白质的基因。这种独特的基因从未被 之前已被表征并被称为电磁感知基因（EPG）。 EPG 已克隆 并在哺乳动物细胞、神经元培养物和大鼠大脑中表达。免疫组织化学 表明 EPG 的表达仅限于哺乳动物细胞膜，并且 可以在特定群体和大鼠的特定大脑区域中表达。钙 对表达 EPG 的哺乳动物细胞和培养神经元进行成像表明，远程 EMF 激活显着增加细胞内钙浓度，表明 细胞兴奋性。此外，大鼠运动皮层 EPG 的无线磁激活诱导 体内对侧前肢的运动诱发反应。我们假设 EPG 技术将能够通过细胞、区域和神经元功能进行无线控制 时间特异性。在这里，我们建议彻底表征蜂窝中的 EPG， 分子和功能水平。我们还将测试EPG技术的有效性 无线控制体内神经元功能。 我们预计这项新技术将改变神经调节的未来， 补充现有的神经调节工具，并极大地有助于理解 复杂的神经回路。

项目成果

The Pig as a Translational Animal Model for Biobehavioral and Neurotrauma Research.

• DOI: 10.3390/biomedicines11082165
• 发表时间: 2023-08-01
• 期刊: Biomedicines
• 影响因子: 4.7