Photochemical regulation of calcium in cell physiology

描述（由申请人提供）：提案的目标是开发用于控制细胞内信号通路的新型光学探针。在过去的15年里，我们制造了许多光学探针，我们称之为笼状化合物，这是细胞生理学领域中所有此类探针中最广泛的。例如，我们开发的笼状钙探针已经被许多实验室用于研究许多细胞类型的生理学的数百个实验中。最近，在这项资助的支持下，笼养的神经递质产生了广泛的影响。任何技术要真正具有变革性，它不仅要解决一个重要的未满足的需求，而且还必须真正起作用，必须是实用的。为了将我们的技术创新转化为现实，我们采取了多学科的方法，

DESCRIPTION (provided by applicant): The goal of proposal is the development of new optical probes for controlling intracellular signaling pathways. Over the past 15 years we have made many optical probes which we call caged compounds that have been the widely of all such probes in the field of cell physiology. For example, the caged calcium probes we have developed have been used in hundreds of experiments by many laboratories studying the physiology of many cell types. More recently, the caged neurotransmitters developed under the aegis of this grant have had wide impact. For any technology to be truly transformative it must not only address a significant unmet need, but it must also really work, it must be practical. In order to translate our technological innovations into reality we take a multidisciplinary approach, combining synthetic organic chemistry and photochemistry, laser photophysics, and cellular physiology. An additional vital feature of our work is that we have forged long-term collaborative relationships with noted physiologists. These interactions have been vital the development of useful and important caged compounds as it is the biological problems that define the probes. In this proposal we seek to address an important gap in the area of optical chemical methods that are used for photochemical probing of intracellular signaling pathways, namely, the ability to accomplish simultaneous, multimodal optical control of parallel signaling processes. The majority, but not all, of the new probes will involve the control of intracellular calcium. The temporal and spatial scales of the effects of changes in calcium are extremely wide, so optical methods that address all these levels are useful in the study of many types of cellular physiology. For example, synaptic transmission uses fast, local changes in calcium, whereas calcium-regulated gene expression uses more sustained changes in cellular calcium. In cardiac myocytes, fast local changes in calcium are converted into global calcium release events, via calcium-induced calcium release, which catalyze contraction. Because calcium is so important, it often is the integration point of symbiotic signaling systems that subtlety regulates calcium itself or use calcium to modulate parallel signaling pathways that are controlled by calcium at some level. The overall goal of this proposal is to develop new photochemical tools that allow bidirectional optical control of these signaling pathways.