@article {49060,
	title = {A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters.},
	journal = {Nature Chemical Biology},
	year = {2018},
	month = {2018 Feb 26},
	abstract = {<p>We developed a new way to engineer complex proteins toward multidimensional specifications using a simple, yet scalable, directed evolution strategy. By robotically picking mammalian cells that were identified, under a microscope, as expressing proteins that simultaneously exhibit several specific properties, we can screen hundreds of thousands of proteins in a library in just a few hours, evaluating each along multiple performance axes. To demonstrate the power of this approach, we created\&nbsp;a genetically encoded fluorescent voltage indicator, simultaneously optimizing its\&nbsp;brightness and membrane localization using our microscopy-guided cell-picking strategy. We produced the high-performance opsin-based fluorescent voltage reporter Archon1 and demonstrated its utility by imaging spiking and millivolt-scale subthreshold and synaptic activity in acute mouse brain slices and in larval zebrafish in vivo. We also measured postsynaptic responses downstream of optogenetically controlled neurons in C. elegans.</p>
},
	issn = {1552-4469},
	doi = {10.1038/s41589-018-0004-9},
	author = {Piatkevich, Kiryl D and Jung, Erica E and Straub, Christoph and Linghu, Changyang and Park, Demian and Suk, Ho-Jun and Hochbaum, Daniel R and Goodwin, Daniel and Pnevmatikakis, Eftychios and Pak, Nikita and Kawashima, Takashi and Yang, Chao-Tsung and Rhoades, Jeffrey L and Shemesh, Or and Asano, Shoh and Yoon, Young-Gyu and Freifeld, Limor and Saulnier, Jessica L and Riegler, Clemens and Engert, Florian and Hughes, Thom and Drobizhev, Mikhail and Szabo, Balint and Ahrens, Misha B and Flavell, Steven W and Sabatini, Bernardo L and Boyden, Edward S}
}
