NDC for the Optical Control of Biological Function

我们的总体目标是开发新的光遗传学工具，其对光信号传导的活性敏感 蛋白质及其表达的细胞。我们将把这些遥控器用于基础研究 了解和操纵肥大细胞分泌的抗原和过敏原（ 引发炎症反应）、穿过视网膜色素上皮的液体吸收（其在视网膜色素上皮中起作用 在囊样黄斑水肿），以及努力重新设计神经元的细胞替代疗法的模型 中枢神经系统神经退化我们已经在另外两个方面取得了重大进展， 代表了我们主要的临床前工作，即努力实现：a）疼痛的治疗和疼痛的分析 和B）在导致光感受器丧失的视网膜病变中恢复视力， 失明我们的方法是开发分子聚焦的方法，用于动态操纵特定的 蛋白质在复杂的细胞环境中，它可以用于完整的组织，事实上，在生活中， 动物其逻辑是使用光作为输入和输出，以探测和控制细胞中的蛋白质功能。而 在过去的20年里，蛋白质功能的光学检测已经取得了显著的进展， 直到最近，控制才成为可能，部分原因是我们的国家数据中心的努力。NDC for the Optical 生物功能控制已经花费了第一个资金期开发利用光快速 开启和关闭细胞中选择蛋白质的功能。我们已经证明了这些策略是 广泛适用于蛋白质类，包括离子通道、G蛋白偶联受体和酶： 细胞中三个最大的信号蛋白家族，以及开发新药物的主要药物靶点， 大药厂

Our overall goals are to develop new optogenetic tools, which sensitize to light the activity of signaling proteins and the cells in which they are expressed. We will employ these remote controls for basic research into understanding and manipulating the mast cell secretion in response to antigens and allergens (which trigger the inflammatory response), fluid absorption across the retinal pigment epithelium (which plays a role in cystoid macular edema), as well as efforts to re-engineer neurons for cell replacement therapy for models of CNS neurodegeneration. We have already made significant progress in two other directions, which represent our major preclinical work, namely efforts toward: a) the treatment of pain and the analysis of pain circuits, and b) the restoration of vision in retinal pathologies that lead to loss of photoreceptors and blindness. Our approach is to develop molecularly focused methods for dynamic manipulation of specific proteins in the complex environment of cells, which can be used in intact tissues, and, indeed, in the live animal. The logic is to use light as both input and output to probe and control protein function in cells. While there has been significant progress in optical detection of protein function over the last 2 decades, remote control has become only possible recently, partly from the efforts of our NDC. The NDC for the Optical Control of Biological Function has spent the first funding period developing methods for using light to rapidly switch on and off the function of select proteins in cells. We have demonstrated that the strategies are broadly applicable across protein classes, including ion channels, G-protein coupled receptors and enzymes: three of the largest families of signaling proteins in cells and major drug targets for the development of new pharmaceuticals.