ABSTRACT High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids

the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against human protein kinases,

including an orphan receptor tyrosine kinase. This blueprint for all-optical screening can be adapted to many drug targets and cellular processes. Access through your institution Buy or

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Michel, J.B. & Kishony, R. _PLoS ONE_ 5, e15179 (2010). Article  Google Scholar  Download references ACKNOWLEDGEMENTS We thank M. Ernst (Medical University of Vienna) for fruitful

discussions, M. Spanova (IST Austria) for technical assistance, R. Chait (IST Austria) for photography, X. Amouretti and B. Harris (BioTek) for hardware specifications, R. Stahel (University

of Zurich) for mesothelioma cells, and D.M. Chudakov (Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry)/Evrogen (Moscow) for mKate2. This work was supported by grants from the

European Union Seventh Framework Programme (CIG-303564 to H.J. and ERC-StG-311166 to S.M.B.N.), the Human Frontier Science Program (RGY0084_2012 to H.J.) and the Herzfelder Foundation (to

M.G.). A.I.-P. was supported by a Ramon Areces fellowship, and E.R. by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF): W 1232) and a FemTech fellowship (3580812

Austrian Research Promotion Agency). AUTHOR INFORMATION Author notes * Sebastian M B Nijman Present address: Present address: Ludwig Institute for Cancer Research, Headington, Oxford, UK.,

AUTHORS AND AFFILIATIONS * Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria Álvaro Inglés-Prieto, Eva Reichhart, Matthias Nowak & Harald Janovjak *

CeMM–Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria Markus K Muellner & Sebastian M B Nijman * Department of Medicine I, Institute of Cancer

Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria Michael Grusch Authors * Álvaro Inglés-Prieto View author publications You can also search for

this author inPubMed Google Scholar * Eva Reichhart View author publications You can also search for this author inPubMed Google Scholar * Markus K Muellner View author publications You can

also search for this author inPubMed Google Scholar * Matthias Nowak View author publications You can also search for this author inPubMed Google Scholar * Sebastian M B Nijman View author

publications You can also search for this author inPubMed Google Scholar * Michael Grusch View author publications You can also search for this author inPubMed Google Scholar * Harald

Janovjak View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS A.I.-P. designed, performed and analyzed all-optical experiments. E.R. designed,

performed and analyzed internal reference experiments. M.K.M., M.N., S.M.B.N. and M.G. designed inhibitor library and experiments and provided reagents. H.J. conceived and supervised the

project and designed and analyzed experiments. A.I.-P., E.R. and H.J. wrote the paper. CORRESPONDING AUTHOR Correspondence to Harald Janovjak. ETHICS DECLARATIONS COMPETING INTERESTS The

authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Results, Supplementary Figures 1–12 and Supplementary Tables 1–3.

(PDF 1461 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Inglés-Prieto, Á., Reichhart, E., Muellner, M. _et al._ Light-assisted small-molecule

screening against protein kinases. _Nat Chem Biol_ 11, 952–954 (2015). https://doi.org/10.1038/nchembio.1933 Download citation * Received: 26 June 2015 * Accepted: 09 September 2015 *

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