Our overall goals are to develop new optogenetic tools, which sensitize to light the activity of signalingproteins and the cells in which they are expressed. We will employ these remote controls for basic researchinto understanding and manipulating the mast cell secretion in response to antigens and allergens (whichtrigger the inflammatory response), fluid absorption across the retinal pigment epithelium (which plays a rolein cystoid macular edema), as well as efforts to re-engineer neurons for cell replacement therapy for modelsof CNS neurodegeneration. We have already made significant progress in two other directions, whichrepresent our major preclinical work, namely efforts toward: a) the treatment of pain and the analysis of paincircuits, and b) the restoration of vision in retinal pathologies that lead to loss of photoreceptors andblindness. Our approach is to develop molecularly focused methods for dynamic manipulation of specificproteins in the complex environment of cells, which can be used in intact tissues, and, indeed, in the liveanimal. The logic is to use light as both input and output to probe and control protein function in cells. Whilethere has been significant progress in optical detection of protein function over the last 2 decades, remotecontrol has become only possible recently, partly from the efforts of our NDC. The NDC for the OpticalControl of Biological Function has spent the first funding period developing methods for using light to rapidlyswitch on and off the function of select proteins in cells. We have demonstrated that the strategies arebroadly 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 newpharmaceuticals.
The aim of the NDC initiative has been to use the tools of nanoscience to develop new approaches to thetreatment of human disease. We have developed nanoscopic chemical photoswitches that enable theremote control ofthe function of signaling proteins in cells using light. We apply these to the restoration ofvision to animal models of blinding diseases that lead to loss ofthe photoreceptor cells ofthe retina and tothe treatment of pain.
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