Optogenetic Tools for Minimally Invasive Therapies

用于微创治疗的光遗传学工具

• 批准号: 1264975
• 负责人: Brian Chow
• 金额: $ 42.55万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1264975&HistoricalAwards=false
• 关键词: Optogenetic; Tools; Minimally; Invasive; Therapies

1264975ChowThe ability to rationally convert a microbial opsin pump into a channel would validate a fundamental hypothesis in ion channel structure-function, which states that a key difference between a pump and a channel is the existence of a gate that prevents backflow of ions by passive conductance and enables active ion translocation against large gradients. This biophysical feat of rational conversion by protein engineering would be the first of its kind. Furthermore, while the activity-dependent safety of neural silencing by proton and chloride pumps has been evaluated in the literature, the creation of optogenetic reagents specifically for the purpose of activity-dependent safety is novel. Moreover, the translationally focused goal of engineering a calcium-free channelrhodopsin to reduce risk of excito-toxicity is in fact opposite to ongoing efforts in the field, which seek to augment calciumconductance to increase sensitivity. The creation of reagents, whose molecular properties are tailored for translational purposes, would represent a new direction in optogenetic reagent development, which to date have focused on pushing the limits of microbial opsin photocurrent magnitude, kinetics, and spectral properties.

将微生物视蛋白泵合理地转化为通道的能力将验证离子通道结构-功能中的基本假设，该假设指出，泵和通道之间的关键区别是存在门，该门通过被动电导防止离子回流，并且能够针对大梯度进行主动离子移位。这种通过蛋白质工程进行合理转换的生物物理壮举将是同类中的第一个。此外，虽然已经在文献中评估了通过质子和氯离子泵进行的神经沉默的活性依赖性安全性，但是专门用于活性依赖性安全性目的的光遗传学试剂的产生是新颖的。此外，工程化无钙通道视紫红质以降低兴奋性毒性风险的目标实际上与该领域正在进行的努力相反，该领域正在寻求增加钙电导以增加敏感性。其分子特性针对翻译目的定制的试剂的创建将代表光遗传学试剂开发的新方向，迄今为止，光遗传学试剂开发的重点是推动微生物视蛋白光电流幅度、动力学和光谱特性的极限。