Opsin Engineering
Optogenetics uses light sensitive proteins called opsins to modulate and monitor the activity of neurons and other cellular states. We are working to extend the properties of opsins through protein engineering.
Glutamate in primary afferents is required for itch transmission
Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses
Machine learning-guided engineering yields high-photocurrent ChR with high light sensitivity
The serotonergic raphe promote sleep
Optogenetics Publications
- Glutamate in primary afferents is required for itch transmission. Cui L., Guo J., Cranfill S.L., Gautam M., Bhattarai J., Olson W., Beattie K., Challis R.C., Wu Q., Song X., Raabe T., Gradinaru V., Ma M., Liu Q., Luo W. Neuron, 2022; doi: 10.1016/j.neuron.2021.12.007. [ Article ]
- Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses. Kahan A., Greenbaum A., Jang M.J., Robinson J.E., Cho J.R., Chen X., Kassraian P., Wagenaar D.A., Gradinaru V. Cell Reports, 2021; doi: 10.1016/j.celrep.2021.109744. [ Article ]
- RecV recombinase system for in vivo targeted optogenomic modifications of single cells or cell populations. You, S., Yuan, P., Ouellette, B., Zhou, T., Mortrud, M., Balaram, P., Chatterjee, S., Wang, Y., Daigle, T. L., Bosiljka, T., Kuang, X., Gong, H., Luo, Q., Zeng, S., Curtright, A., Dhaka, A., Kahan, A., Gradinaru, V., Chrapkiewicz, R., Schnitzer, M., Zeng, H., Cetin, A. Nature Methods, 2020; doi: 10.1038/s41592-020-0774-3. [ Article | Open access link ]
- Gut-seeded α-Synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice. Challis, C., Hori, A., Sampson, T. R., Yoo, B. B., Challis, R. C., Hamilton, A. M., Mazmanian, S. K., Volpicelli-Daley, L. A., Gradinaru, V. Nature Neuroscience, 2020; doi: 10.1038/s41593-020-0589-7. [ Article | Open access link | Caltech News Release ]
- Machine learning-guided channelrhodopsin engineering enables minimally invasive optogenetics. Bedbrook, C. N., Yang, K. K., Robinson, J. E., Mackey, E. D., Gradinaru, V., & Arnold, F. H. Nature Methods, 2019; doi: 10.1038/s41592-019-0583-8. [ Article | Open access link | Caltech News Release ]
- Optical dopamine monitoring with dLight1 reveals mesolimbic phenotypes in a mouse model of neurofibromatosis type 1. Robinson, J. E., Coughlin, G. M., Hori, A. M., Cho, J. R., Mackey, E. D., Turan, Z., Patriarchi, T., Tian, L., Gradinaru, V. eLife, 2019; doi: 10.7554/eLife.48983. [ Article ]
- The Serotonergic Raphe Promote Sleep in Zebrafish and Mice.. Oikonomou, G., Altermatt, M., Zhang, R., Coughlin, G. M., Montz, C., Gradinaru, V., & Prober, D. A. Neuron, 2019; doi: 10.1016/j.neuron.2019.05.038. [ Article | Video abstract | Caltech News Release ]
- Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies. Rajendran, P. S., Challis, R. C., Fowlkes, C. C., Hanna, P., Tompkins, J. D., Jordan, M. C., Hiyari, S., Gabris-Weber, B. A., Greenbaum, A., Chan, K. Y., Deverman, B. E., Münzberg, H., Ardell, J. L., Salama, G., Gradinaru, V., Shivkumar, K. Nature Communications, 2019; doi: 10.1038/s41467-019-09770-1. [ Article ]
- Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization. Bedbrook CN, Yang KK, Rice AJ, Gradinaru V, Arnold FH. PLoS Comput Biol. 2017 Oct 23;13(10):e1005786. doi: 10.1371/journal.pcbi.1005786. [ Article ]
- Q&A: How can advances in tissue clearing and optogenetics contribute to our understanding of normal and diseased biology. Greenbaum A., Jang M.J., Challis C., Gradinaru V. BMC Biol., 2017; doi: 10.1186/s12915-017-0421-3. [ Article ]
- Structure-guided SCHEMA recombination generates diverse chimeric channelrhodopsins. Bedbrook, C.N., Rice, A.J., Yang, K.K., Ding, X., Chen, E., LeProust, E.M., Gradinaru, V., Arnold, F.H. Proc Natl Acad Sci, 2017. [ Article ]
- Directed evolution of a bright near-infrared fluorescent rhodopsin using a synthetic chromophore. Herwig, L., Rice, A.J., Bedbrook, C.N., Zhang, R.K., Lignell, A., Cahn, J.K.B., Renata, H., Dodani, S.C., Cho, I., Cai, L., Gradinaru, V., Arnold, F.H. Cell Chem Biol, 2017; doi:10.1016/j.chembiol.2017.02.008. [ Article | Nature Methods Research Highlights ]
- Neuroscience: Fluorescent boost for voltage sensors. Gradinaru, V.; Flytzanis, N.C. Nature, 2016; 529, 469-470. [ Article ]
- Archaerhodopsin variants with enhanced voltage-sensitive fluorescence in mammalian and Caenorhabditis elegans neurons. Flytzanis*, N.C.; Bedbrook*, C.N.; Chiu, H.; Engqvist, M.K.M.; Xiao, C.; Chan, K.Y.; Sternberg, P.W.; Arnold, F.H.; Gradinaru, V. Nat Commu, 2014; 5: 4894. [ Article | Caltech News Release | Nature Methods Research Highlights | SPIE Newsroom | Archer 1 Plasmid on Addgene ]
- Directed evolution of a far-red fluorescent rhodopsin. McIsaac, R.S.; Engqvist, M.K.M.; Wannier, T.; Rosenthal, A.Z.; Herwig, L.; Flytzanis, N.C.; Imasheva, E.S.; Lanyi, J.K.; Balashov, S.P.; Gradinaru, V.; Arnold, F.H. Proc Natl Acad Sci USA 2014; doi: 10.1073/pnas.1413987111. [ Article ]