The goal of proposal is the development of new optical probes for controlling intracellular signaling pathways. Over the past 20 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. 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 using regular lasers widely available on all confocal microscopes. Secondly, we will develop new optical probes for highly efficient two-photon excitation. In collaboration with physical chemists and cardiac physiologists we will make a test these new probes. The overall goal of this proposal is to develop new photochemical tools that allow precise optical control of intracellular signaling pathways.
Optical methods are a primary technique for the study of cellular physiology. This research concerns the development of new optical probes that will enable simultaneous photocontrol of two intracellular signaling systems for the first time. Since almost all cell signaling is bidirectional or symbiotic, these new methods will revolutionize our ability to control function and therefore uncover many fresh details of cell physiology.
| Passlick, Stefan; Richers, Matthew T; Ellis-Davies, Graham C R (2018) Thermodynamically Stable, Photoreversible Pharmacology in Neurons with One- and Two-Photon Excitation. Angew Chem Int Ed Engl 57:12554-12557 |
| Richers, Matthew T; Tran, Dinh Du; Wachtveitl, Josef et al. (2018) Coumarin-diene photoswitches for rapid and efficient isomerization with visible light. Chem Commun (Camb) 54:4983-4986 |
| Passlick, Stefan; Ellis-Davies, Graham C R (2018) Comparative one- and two-photon uncaging of MNI-glutamate and MNI-kainate on hippocampal CA1 neurons. J Neurosci Methods 293:321-328 |
| Agarwal, Hitesh K; Zhai, Shenyu; Surmeier, D James et al. (2017) Intracellular Uncaging of cGMP with Blue Light. ACS Chem Neurosci 8:2139-2144 |
| Passlick, Stefan; Kramer, Paul F; Richers, Matthew T et al. (2017) Two-color, one-photon uncaging of glutamate and GABA. PLoS One 12:e0187732 |
| Richers, Matthew T; Amatrudo, Joseph M; Olson, Jeremy P et al. (2017) Cloaked Caged Compounds: Chemical Probes for Two-Photon Optoneurobiology. Angew Chem Int Ed Engl 56:193-197 |
| Howarth, Clare; Sutherland, Brad; Choi, Hyun B et al. (2017) A Critical Role for Astrocytes in Hypercapnic Vasodilation in Brain. J Neurosci 37:2403-2414 |
| Agarwal, Hitesh K; Janicek, Radoslav; Chi, San-Hui et al. (2016) Calcium Uncaging with Visible Light. J Am Chem Soc 138:3687-93 |
| Sajo, Mari; Ellis-Davies, Graham; Morishita, Hirofumi (2016) Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex. J Neurosci 36:9472-8 |
| Kantevari, Srinivas; Passlick, Stefan; Kwon, Hyung-Bae et al. (2016) Development of Anionically Decorated Caged Neurotransmitters: In Vitro Comparison of 7-Nitroindolinyl- and 2-(p-Phenyl-o-nitrophenyl)propyl-Based Photochemical Probes. Chembiochem 17:953-61 |
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