Developing novel optical tools to interrogate cellular signaling
Opto-CRAC | Optical control of calcium signaling and immune response
Converting SOC to LOC: light-operated calcium entry
OptoCRAC | Illuminating calcium signaling with LOV domain
The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. We aim to develop an NIR-stimulable optogenetic platform (termed “Opto-CRAC”) that selectively and remotely controls Ca2+ oscillations and Ca2+-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window will be shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca2+-dependent signaling and optogenetic modulation of immunoinflammatory responses.
In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded “photoactivatable adjuvant” to improve antigen-specific immune responses to specifically destruct tumor cells. Our study represents a solid step forward towards the goal of achieving remote control of Ca2+-modulated activities with tailored function.
He L*, Zhang Y*, Ma G*, Tan P*, Li Z, Zang S, Wu X, Jing J, Fang S, Zhou L, Wang Y, Huang Y, Hogan PG, Han G, Zhou Y. Near-infrared photoactivatable control of ca2+ signaling and optogenetic immunomodulation. eLife. 2015 (accepted)
Jing J*, He L*, Sun A*, Quintana A*, Ding Y*, Ma G, Tan P, Liang X, Zheng X, Chen L, Shi X, Zhang SL, Zhong L, Huang Y, Dong MQ, Walker CL, Hogan PG, Wang Y and Zhou Y. Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of Ca2+ influx. Nature Cell Biology. 2015,17:1339-4.