@article{5984,
  abstract     = {G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.},
  author       = {Morri, Maurizio and Sanchez-Romero, Inmaculada and Tichy, Alexandra-Madelaine and Kainrath, Stephanie and Gerrard, Elliot J. and Hirschfeld, Priscila and Schwarz, Jan and Janovjak, Harald L},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  number       = {1},
  publisher    = {Springer Nature},
  title        = {{Optical functionalization of human class A orphan G-protein-coupled receptors}},
  doi          = {10.1038/s41467-018-04342-1},
  volume       = {9},
  year         = {2018},
}

@article{538,
  abstract     = {Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung. },
  author       = {Kainrath, Stephanie and Stadler, Manuela and Gschaider-Reichhart, Eva and Distel, Martin and Janovjak, Harald L},
  journal      = {Angewandte Chemie},
  number       = {16},
  pages        = {4679 -- 4682},
  publisher    = {Wiley},
  title        = {{Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen}},
  doi          = {10.1002/ange.201611998},
  volume       = {129},
  year         = {2017},
}

@article{1026,
  abstract     = {The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.},
  author       = {Agus, Viviana and Janovjak, Harald L},
  issn         = {09581669},
  journal      = {Current Opinion in Biotechnology},
  pages        = {8 -- 14},
  publisher    = {Elsevier},
  title        = {{Optogenetic methods in drug screening: Technologies and applications}},
  doi          = {10.1016/j.copbio.2017.02.006},
  volume       = {48},
  year         = {2017},
}

@article{1440,
  author       = {Janovjak, Harald L},
  journal      = {Structure},
  number       = {2},
  pages        = {213 -- 215},
  publisher    = {Cell Press},
  title        = {{Light at the end of the protein: Crystal structure of a C-terminal light-sensing domain}},
  doi          = {10.1016/j.str.2016.01.002},
  volume       = {24},
  year         = {2016},
}

@article{1441,
  abstract     = {Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an optimized sensory domain of the cyanobacterial phytochrome 1 can be expressed robustly and without cytotoxicity in human cells. We then applied this domain to induce the dimerization of two receptor tyrosine kinases—the fibroblast growth factor receptor 1 and the neurotrophin receptor trkB. This new optogenetic method was then used to activate the MAPK/ERK pathway non-invasively in mammalian tissue and in multicolor cell-signaling experiments. The light-controlled dimerizer and red-light-activated receptor tyrosine kinases will prove useful to regulate a variety of cellular processes with light. Go deep with red: The sensory domain (S) of the cyanobacterial phytochrome 1 (CPH1) was repurposed to induce the homodimerization of proteins in living cells by red light. By using this domain, light-activated protein kinases were engineered that can be activated orthogonally from many fluorescent proteins and through mammalian tissue. Pr/Pfr=red-/far-red-absorbing state of CPH1.},
  author       = {Gschaider-Reichhart, Eva and Inglés Prieto, Álvaro and Tichy, Alexandra-Madelaine and Mckenzie, Catherine and Janovjak, Harald L},
  journal      = {Angewandte Chemie - International Edition},
  number       = {21},
  pages        = {6339 -- 6342},
  publisher    = {Wiley},
  title        = {{A phytochrome sensory domain permits receptor activation by red light}},
  doi          = {10.1002/anie.201601736},
  volume       = {55},
  year         = {2016},
}

@article{1678,
  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.},
  author       = {Inglés Prieto, Álvaro and Gschaider-Reichhart, Eva and Muellner, Markus and Nowak, Matthias and Nijman, Sebastian and Grusch, Michael and Janovjak, Harald L},
  journal      = {Nature Chemical Biology},
  number       = {12},
  pages        = {952 -- 954},
  publisher    = {Nature Publishing Group},
  title        = {{Light-assisted small-molecule screening against protein kinases}},
  doi          = {10.1038/nchembio.1933},
  volume       = {11},
  year         = {2015},
}