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： 在活大脑中操纵神经元功能的能力都对 人类健康和基础科学。在过去的半个世纪中，神经元通过植入 特定大脑区域中的微电极已用于缓解与 各种神经元疾病。但是，这种方法不需要植入复合物， 依赖外部电源的大型且广泛的电子设备， 神经刺激的实际放置意外和不良副作用 电极通常会产生。最近，分子和合成生物学的重大进展 促进了接收器和频道的克隆和优化，以调制 响应光，化学或温度的神经元功能。但是，这些控制 蛋白质需要激活剂的侵入性递送。因此，非侵入性，遥控器控制 可以以非侵入性方式操纵特定神经元种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 通过非侵入性的传播来远程控制细胞功能的新方法 电磁场（EMF）。使用表达克隆，我们已经识别并克隆了一个 编码对EMF反应的蛋白质的基因。这个独特的基因从来没有 以前和称为电磁知觉基因（EPG）。 EPG被克隆 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 可以在特定人群和大鼠的特定大脑区域中表达。钙 表达EPG的哺乳动物细胞和培养的神经元的成像证明了远程 EMF激活显着增加了细胞内钙的浓度，表明 细胞令人兴奋。此外，大鼠运动皮层诱导的EPG无线磁激活 运动诱发了体内对侧前肢的反应。我们假设EPG 技术将通过细胞，区域和 临时特异性。在这里，我们建议在细胞中彻底表征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，并为理解 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