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，使信号活动变得敏感 蛋白质和表达蛋白质的细胞。我们将把这些遥控器用于基础研究 理解和操纵肥大细胞分泌以响应抗原和过敏原(这是 触发炎症反应)，液体通过视网膜色素上皮吸收(这在 黄斑囊样水肿)，以及为模型细胞替代治疗而重新设计神经元的努力 中枢神经系统退行性变。我们已经在另外两个方向取得了重大进展，这两个方向是 代表我们的主要临床前工作，即努力：a)治疗疼痛和分析疼痛 B)导致光感受器丧失的视网膜病变的视力恢复，以及 失明。我们的方法是开发分子聚焦的方法来动态操纵特定的 细胞复杂环境中的蛋白质，可以在完整的组织中使用，甚至在活体中使用 动物。其逻辑是利用光作为输入和输出来探测和控制细胞中的蛋白质功能。而当 在过去的20年里，光学检测蛋白质功能取得了重大进展。 控制只是在最近才成为可能，部分原因是我们NDC的努力。面向光纤的网络数据中心 生物功能控制已经花费了第一个资助期来开发快速利用光的方法 打开和关闭细胞中选定蛋白质的功能。我们已经证明了这些策略是 广泛适用于各种蛋白质类别，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，也是新基因开发的主要药物靶点 制药公司。

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.