[{"ddc":["570"],"date_published":"2021-04-01T00:00:00Z","oa":1,"publication_status":"published","has_accepted_license":"1","intvolume":" 17","citation":{"mla":"Inglés Prieto, Álvaro, et al. “Optogenetic Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” PLoS Genetics, vol. 17, no. 4, Public Library of Science, 2021, p. e1009479, doi:10.1371/journal.pgen.1009479.","ista":"Inglés Prieto Á, Furthmann N, Crossman SH, Tichy AM, Hoyer N, Petersen M, Zheden V, Bicher J, Gschaider-Reichhart E, György A, Siekhaus DE, Soba P, Winklhofer KF, Janovjak HL. 2021. Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS genetics. 17(4), e1009479.","apa":"Inglés Prieto, Á., Furthmann, N., Crossman, S. H., Tichy, A. M., Hoyer, N., Petersen, M., … Janovjak, H. L. (2021). Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1009479","ama":"Inglés Prieto Á, Furthmann N, Crossman SH, et al. Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS genetics. 2021;17(4):e1009479. doi:10.1371/journal.pgen.1009479","short":"Á. Inglés Prieto, N. Furthmann, S.H. Crossman, A.M. Tichy, N. Hoyer, M. Petersen, V. Zheden, J. Bicher, E. Gschaider-Reichhart, A. György, D.E. Siekhaus, P. Soba, K.F. Winklhofer, H.L. Janovjak, PLoS Genetics 17 (2021) e1009479.","ieee":"Á. Inglés Prieto et al., “Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease,” PLoS genetics, vol. 17, no. 4. Public Library of Science, p. e1009479, 2021.","chicago":"Inglés Prieto, Álvaro, Nikolas Furthmann, Samuel H. Crossman, Alexandra Madelaine Tichy, Nina Hoyer, Meike Petersen, Vanessa Zheden, et al. “Optogenetic Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” PLoS Genetics. Public Library of Science, 2021. https://doi.org/10.1371/journal.pgen.1009479."},"status":"public","external_id":{"isi":["000640606700001"]},"volume":17,"date_created":"2021-05-02T22:01:29Z","file_date_updated":"2021-05-04T09:05:27Z","page":"e1009479","type":"journal_article","oa_version":"Published Version","month":"04","abstract":[{"text":"Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair.","lang":"eng"}],"date_updated":"2023-08-08T13:17:47Z","_id":"9363","acknowledgement":"We thank R. Cagan, A. Whitworth and J. Nagpal for fly lines and advice, S. Herlitze for provision of a tissue culture illuminator, and Verian Bader for help with statistical analysis.","year":"2021","doi":"10.1371/journal.pgen.1009479","quality_controlled":"1","publication_identifier":{"eissn":["15537404"]},"isi":1,"issue":"4","language":[{"iso":"eng"}],"title":"Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease","author":[{"id":"2A9DB292-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5409-8571","full_name":"Inglés Prieto, Álvaro","last_name":"Inglés Prieto","first_name":"Álvaro"},{"full_name":"Furthmann, Nikolas","first_name":"Nikolas","last_name":"Furthmann"},{"full_name":"Crossman, Samuel H.","first_name":"Samuel H.","last_name":"Crossman"},{"first_name":"Alexandra Madelaine","last_name":"Tichy","full_name":"Tichy, Alexandra Madelaine"},{"full_name":"Hoyer, Nina","first_name":"Nina","last_name":"Hoyer"},{"full_name":"Petersen, Meike","first_name":"Meike","last_name":"Petersen"},{"id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","full_name":"Zheden, Vanessa","last_name":"Zheden","first_name":"Vanessa"},{"last_name":"Bicher","first_name":"Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Bicher, Julia"},{"last_name":"Gschaider-Reichhart","first_name":"Eva","full_name":"Gschaider-Reichhart, Eva","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7218-7738"},{"first_name":"Attila","last_name":"György","full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","first_name":"Daria E","last_name":"Siekhaus"},{"last_name":"Soba","first_name":"Peter","full_name":"Soba, Peter"},{"full_name":"Winklhofer, Konstanze F.","last_name":"Winklhofer","first_name":"Konstanze F."},{"last_name":"Janovjak","first_name":"Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","full_name":"Janovjak, Harald L"}],"day":"01","file":[{"checksum":"82a74668f863e8dfb22fdd4f845c92ce","file_id":"9369","date_updated":"2021-05-04T09:05:27Z","access_level":"open_access","date_created":"2021-05-04T09:05:27Z","file_name":"2021_PLOS_Ingles-Prieto.pdf","success":1,"creator":"kschuh","file_size":3072764,"content_type":"application/pdf","relation":"main_file"}],"publication":"PLoS genetics","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","scopus_import":"1","publisher":"Public Library of Science","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"EM-Fac"},{"_id":"LoSw"},{"_id":"DaSi"}]},{"extern":"1","intvolume":" 4","citation":{"short":"T. Rauschendorfer, S. Gurri, I. Heggli, L. Maddaluno, M. Meyer, Á. Inglés Prieto, H.L. Janovjak, S. Werner, Life Science Alliance 4 (2021).","ieee":"T. Rauschendorfer et al., “Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice,” Life Science Alliance, vol. 4, no. 11. Life Science Alliance, 2021.","chicago":"Rauschendorfer, Theresa, Selina Gurri, Irina Heggli, Luigi Maddaluno, Michael Meyer, Álvaro Inglés Prieto, Harald L Janovjak, and Sabine Werner. “Acute and Chronic Effects of a Light-Activated FGF Receptor in Keratinocytes in Vitro and in Mice.” Life Science Alliance. Life Science Alliance, 2021. https://doi.org/10.26508/lsa.202101100.","mla":"Rauschendorfer, Theresa, et al. “Acute and Chronic Effects of a Light-Activated FGF Receptor in Keratinocytes in Vitro and in Mice.” Life Science Alliance, vol. 4, no. 11, e202101100, Life Science Alliance, 2021, doi:10.26508/lsa.202101100.","ista":"Rauschendorfer T, Gurri S, Heggli I, Maddaluno L, Meyer M, Inglés Prieto Á, Janovjak HL, Werner S. 2021. Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice. Life Science Alliance. 4(11), e202101100.","apa":"Rauschendorfer, T., Gurri, S., Heggli, I., Maddaluno, L., Meyer, M., Inglés Prieto, Á., … Werner, S. (2021). Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice. Life Science Alliance. Life Science Alliance. https://doi.org/10.26508/lsa.202101100","ama":"Rauschendorfer T, Gurri S, Heggli I, et al. Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice. Life Science Alliance. 2021;4(11). doi:10.26508/lsa.202101100"},"status":"public","external_id":{"pmid":["34548382"]},"date_published":"2021-09-21T00:00:00Z","ddc":["576"],"publication_status":"published","oa":1,"has_accepted_license":"1","_id":"10144","acknowledgement":"We thank Connor Richterich and Patricia Reinert, ETH Zurich, for invaluable experimental help; Manuela Pérez Berlanga, University Zurich, for help with the confocal imaging; Lukas Fischer for help with electrical engineering; Thomas Hennek, Sol Taguinod, and Dr. Stephan Sonntag, EPIC Phenomics Center, ETH Zürich, for the generation and maintenance of K14-OptoR2 mice; and Dr. Petra Boukamp, Leibniz Institute, Düsseldorf, Germany, for early-passage HaCaT keratinocytes. This work was supported by the ETH Zurich (grant ETH-06 15-1 to S Werner and L Maddaluno), the Swiss National Science Foundation (grant 31003B-189364 to S Werner), and a Marie Curie postdoctoral fellowship from the European Union (to L Maddaluno).","year":"2021","volume":4,"date_created":"2021-10-17T22:01:16Z","file_date_updated":"2021-10-18T14:48:06Z","date_updated":"2022-08-31T14:01:56Z","abstract":[{"text":"FGFs and their high-affinity receptors (FGFRs) play key roles in development, tissue repair, and disease. Because FGFRs bind overlapping sets of ligands, their individual functions cannot be determined using ligand stimulation. Here, we generated a light-activated FGFR2 variant (OptoR2) to selectively activate signaling by the major FGFR in keratinocytes. Illumination of OptoR2-expressing HEK 293T cells activated FGFR signaling with remarkable temporal precision and promoted cell migration and proliferation. In murine and human keratinocytes, OptoR2 activation rapidly induced the classical FGFR signaling pathways and expression of FGF target genes. Surprisingly, multi-level counter-regulation occurred in keratinocytes in vitro and in transgenic mice in vivo, including OptoR2 down-regulation and loss of responsiveness to light activation. These results demonstrate unexpected cell type-specific limitations of optogenetic FGFRs in long-term in vitro and in vivo settings and highlight the complex consequences of transferring optogenetic cell signaling tools into their relevant cellular contexts.","lang":"eng"}],"type":"journal_article","month":"09","oa_version":"Published Version","language":[{"iso":"eng"}],"issue":"11","doi":"10.26508/lsa.202101100","quality_controlled":"1","publication_identifier":{"eissn":["2575-1077"]},"publication":"Life Science Alliance","scopus_import":"1","article_processing_charge":"Yes","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publisher":"Life Science Alliance","pmid":1,"title":"Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice","article_number":"e202101100","author":[{"full_name":"Rauschendorfer, Theresa","last_name":"Rauschendorfer","first_name":"Theresa"},{"full_name":"Gurri, Selina","first_name":"Selina","last_name":"Gurri"},{"full_name":"Heggli, Irina","first_name":"Irina","last_name":"Heggli"},{"full_name":"Maddaluno, Luigi","last_name":"Maddaluno","first_name":"Luigi"},{"full_name":"Meyer, Michael","last_name":"Meyer","first_name":"Michael"},{"id":"2A9DB292-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5409-8571","full_name":"Inglés Prieto, Álvaro","last_name":"Inglés Prieto","first_name":"Álvaro"},{"orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","full_name":"Janovjak, Harald L","last_name":"Janovjak","first_name":"Harald L"},{"full_name":"Werner, Sabine","first_name":"Sabine","last_name":"Werner"}],"day":"21","file":[{"creator":"cchlebak","relation":"main_file","content_type":"application/pdf","file_size":2055981,"success":1,"file_name":"2021_LifeScAlliance_Rauschendorfer.pdf","access_level":"open_access","date_created":"2021-10-18T14:48:06Z","checksum":"89fb95b211dbe8678809e7cca4626952","date_updated":"2021-10-18T14:48:06Z","file_id":"10152"}]},{"citation":{"ama":"Kainrath S, Janovjak HL. Design and application of light-regulated receptor tyrosine kinases. In: Niopek D, ed. Photoswitching Proteins. Vol 2173. MIMB. Springer Nature; 2020:233-246. doi:10.1007/978-1-0716-0755-8_16","apa":"Kainrath, S., & Janovjak, H. L. (2020). Design and application of light-regulated receptor tyrosine kinases. In D. Niopek (Ed.), Photoswitching Proteins (Vol. 2173, pp. 233–246). Springer Nature. https://doi.org/10.1007/978-1-0716-0755-8_16","ista":"Kainrath S, Janovjak HL. 2020.Design and application of light-regulated receptor tyrosine kinases. In: Photoswitching Proteins. Methods in Molecular Biology, vol. 2173, 233–246.","mla":"Kainrath, Stephanie, and Harald L. Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” Photoswitching Proteins, edited by Dominik Niopek, vol. 2173, Springer Nature, 2020, pp. 233–46, doi:10.1007/978-1-0716-0755-8_16.","chicago":"Kainrath, Stephanie, and Harald L Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” In Photoswitching Proteins, edited by Dominik Niopek, 2173:233–46. MIMB. Springer Nature, 2020. https://doi.org/10.1007/978-1-0716-0755-8_16.","ieee":"S. Kainrath and H. L. Janovjak, “Design and application of light-regulated receptor tyrosine kinases,” in Photoswitching Proteins, vol. 2173, D. Niopek, Ed. Springer Nature, 2020, pp. 233–246.","short":"S. Kainrath, H.L. Janovjak, in:, D. Niopek (Ed.), Photoswitching Proteins, Springer Nature, 2020, pp. 233–246."},"language":[{"iso":"eng"}],"intvolume":" 2173","series_title":"MIMB","status":"public","editor":[{"first_name":"Dominik","last_name":"Niopek","full_name":"Niopek, Dominik"}],"alternative_title":["Methods in Molecular Biology"],"date_published":"2020-07-11T00:00:00Z","doi":"10.1007/978-1-0716-0755-8_16","publication_identifier":{"eissn":["19406029"],"eisbn":["9781071607558"]},"publication_status":"published","article_processing_charge":"No","scopus_import":"1","_id":"8173","publication":"Photoswitching Proteins","department":[{"_id":"CaGu"}],"year":"2020","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","date_created":"2020-07-26T22:01:03Z","title":"Design and application of light-regulated receptor tyrosine kinases","volume":2173,"type":"book_chapter","oa_version":"None","month":"07","day":"11","abstract":[{"text":"Understanding how the activity of membrane receptors and cellular signaling pathways shapes cell behavior is of fundamental interest in basic and applied research. Reengineering receptors to react to light instead of their cognate ligands allows for generating defined signaling inputs with high spatial and temporal precision and facilitates the dissection of complex signaling networks. Here, we describe fundamental considerations in the design of light-regulated receptor tyrosine kinases (Opto-RTKs) and appropriate control experiments. We also introduce methods for transient receptor expression in HEK293 cells, quantitative assessment of signaling activity in reporter gene assays, semiquantitative assessment of (in)activation time courses through Western blot (WB) analysis, and easy to implement light stimulation hardware.","lang":"eng"}],"date_updated":"2021-01-12T08:17:17Z","page":"233-246","author":[{"last_name":"Kainrath","first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","full_name":"Kainrath, Stephanie"},{"full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","first_name":"Harald L","last_name":"Janovjak"}]},{"doi":"10.1016/j.neuron.2020.08.030","quality_controlled":"1","publication_identifier":{"issn":["08966273"],"eissn":["10974199"]},"isi":1,"language":[{"iso":"eng"}],"issue":"5","title":"LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia","author":[{"first_name":"Christian","last_name":"Henneberger","full_name":"Henneberger, Christian"},{"last_name":"Bard","first_name":"Lucie","full_name":"Bard, Lucie"},{"first_name":"Aude","last_name":"Panatier","full_name":"Panatier, Aude"},{"full_name":"Reynolds, James P.","last_name":"Reynolds","first_name":"James P."},{"full_name":"Kopach, Olga","last_name":"Kopach","first_name":"Olga"},{"last_name":"Medvedev","first_name":"Nikolay I.","full_name":"Medvedev, Nikolay I."},{"full_name":"Minge, Daniel","last_name":"Minge","first_name":"Daniel"},{"first_name":"Michel K.","last_name":"Herde","full_name":"Herde, Michel K."},{"full_name":"Anders, Stefanie","last_name":"Anders","first_name":"Stefanie"},{"full_name":"Kraev, Igor","first_name":"Igor","last_name":"Kraev"},{"full_name":"Heller, Janosch P.","last_name":"Heller","first_name":"Janosch P."},{"full_name":"Rama, Sylvain","last_name":"Rama","first_name":"Sylvain"},{"full_name":"Zheng, Kaiyu","first_name":"Kaiyu","last_name":"Zheng"},{"first_name":"Thomas P.","last_name":"Jensen","full_name":"Jensen, Thomas P."},{"first_name":"Inmaculada","last_name":"Sanchez-Romero","full_name":"Sanchez-Romero, Inmaculada","id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jackson, Colin J.","first_name":"Colin J.","last_name":"Jackson"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L","last_name":"Janovjak"},{"last_name":"Ottersen","first_name":"Ole Petter","full_name":"Ottersen, Ole Petter"},{"first_name":"Erlend Arnulf","last_name":"Nagelhus","full_name":"Nagelhus, Erlend Arnulf"},{"full_name":"Oliet, Stephane H.R.","last_name":"Oliet","first_name":"Stephane H.R."},{"full_name":"Stewart, Michael G.","last_name":"Stewart","first_name":"Michael G."},{"full_name":"Nägerl, U. VAlentin","first_name":"U. VAlentin","last_name":"Nägerl"},{"last_name":"Rusakov","first_name":"Dmitri A. ","full_name":"Rusakov, Dmitri A. "}],"day":"09","file":[{"content_type":"application/pdf","relation":"main_file","file_size":7518960,"creator":"dernst","success":1,"file_name":"2020_Neuron_Henneberger.pdf","date_created":"2020-12-10T14:42:09Z","access_level":"open_access","date_updated":"2020-12-10T14:42:09Z","file_id":"8939","checksum":"054562bb50165ef9a1f46631c1c5e36b"}],"publication":"Neuron","scopus_import":"1","article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Elsevier","pmid":1,"department":[{"_id":"HaJa"}],"date_published":"2020-12-09T00:00:00Z","ddc":["570"],"publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":" 108","citation":{"ista":"Henneberger C, Bard L, Panatier A, Reynolds JP, Kopach O, Medvedev NI, Minge D, Herde MK, Anders S, Kraev I, Heller JP, Rama S, Zheng K, Jensen TP, Sanchez-Romero I, Jackson CJ, Janovjak HL, Ottersen OP, Nagelhus EA, Oliet SHR, Stewart MG, Nägerl UVa, Rusakov DA. 2020. LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia. Neuron. 108(5), P919–936.E11.","mla":"Henneberger, Christian, et al. “LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia.” Neuron, vol. 108, no. 5, Elsevier, 2020, p. P919–936.E11, doi:10.1016/j.neuron.2020.08.030.","apa":"Henneberger, C., Bard, L., Panatier, A., Reynolds, J. P., Kopach, O., Medvedev, N. I., … Rusakov, D. A. (2020). LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.08.030","ama":"Henneberger C, Bard L, Panatier A, et al. LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia. Neuron. 2020;108(5):P919-936.E11. doi:10.1016/j.neuron.2020.08.030","short":"C. Henneberger, L. Bard, A. Panatier, J.P. Reynolds, O. Kopach, N.I. Medvedev, D. Minge, M.K. Herde, S. Anders, I. Kraev, J.P. Heller, S. Rama, K. Zheng, T.P. Jensen, I. Sanchez-Romero, C.J. Jackson, H.L. Janovjak, O.P. Ottersen, E.A. Nagelhus, S.H.R. Oliet, M.G. Stewart, U.Va. Nägerl, D.A. Rusakov, Neuron 108 (2020) P919–936.E11.","ieee":"C. Henneberger et al., “LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia,” Neuron, vol. 108, no. 5. Elsevier, p. P919–936.E11, 2020.","chicago":"Henneberger, Christian, Lucie Bard, Aude Panatier, James P. Reynolds, Olga Kopach, Nikolay I. Medvedev, Daniel Minge, et al. “LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.08.030."},"external_id":{"pmid":["32976770"],"isi":["000603428000010"]},"status":"public","volume":108,"date_created":"2020-10-18T22:01:38Z","file_date_updated":"2020-12-10T14:42:09Z","page":"P919-936.E11","date_updated":"2023-08-22T09:59:29Z","abstract":[{"text":"Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localization reveal that LTP induction thus prompts spatial retreat of astroglial glutamate transporters, boosting glutamate spillover and NMDA-receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which a memory trace at one synapse could alter signal handling by multiple neighboring connections.","lang":"eng"}],"month":"12","type":"journal_article","oa_version":"Published Version","_id":"8674","acknowledgement":"We thank J. Angibaud for organotypic cultures and R. Chereau and J. Tonnesen for help with the STED microscope; also D. Gonzales and the Neurocentre Magendie INSERM U1215 Genotyping Platform, for breeding management and genotyping. This work was supported by the Wellcome Trust Principal Fellowships 101896 and 212251, ERC Advanced Grant 323113, ERC Proof-of-Concept Grant 767372, EC FP7 ITN 606950, and EU CSA 811011 (D.A.R.); NRW-Rückkehrerpogramm, UCL Excellence Fellowship, German Research Foundation (DFG) SPP1757 and SFB1089 (C.H.); Human Frontiers Science Program (C.H., C.J.J., and H.J.); EMBO Long-Term Fellowship (L.B.); Marie Curie FP7 PIRG08-GA-2010-276995 (A.P.), ASTROMODULATION (S.R.); Equipe FRM DEQ 201 303 26519, Conseil Régional d’Aquitaine R12056GG, INSERM (S.H.R.O.); ANR SUPERTri, ANR Castro (ANR-17-CE16-0002), R-13-BSV4-0007-01, Université de Bordeaux, labex BRAIN (S.H.R.O. and U.V.N.); CNRS (A.P., S.H.R.O., and U.V.N.); HFSP, ANR CEXC, and France-BioImaging ANR-10-INSB-04 (U.V.N.); and FP7 MemStick Project No. 201600 (M.G.S.).","year":"2020"},{"project":[{"grant_number":"303564","_id":"25548C20-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Microbial Ion Channels for Synthetic Neurobiology"},{"grant_number":"I03630","call_identifier":"FWF","_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants"},{"grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0165-0270"]},"doi":"10.1016/j.jneumeth.2018.11.018","quality_controlled":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Elsevier","department":[{"_id":"HaJa"},{"_id":"Bio"}],"pmid":1,"publication":"Journal of Neuroscience Methods","article_type":"original","ec_funded":1,"scopus_import":"1","article_processing_charge":"No","author":[{"full_name":"Mckenzie, Catherine","id":"3EEDE19A-F248-11E8-B48F-1D18A9856A87","first_name":"Catherine","last_name":"Mckenzie"},{"last_name":"Spanova","first_name":"Miroslava","full_name":"Spanova, Miroslava","id":"44A924DC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alexander J","last_name":"Johnson","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2739-8843","full_name":"Johnson, Alexander J"},{"id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","full_name":"Kainrath, Stephanie","last_name":"Kainrath","first_name":"Stephanie"},{"last_name":"Zheden","first_name":"Vanessa","full_name":"Zheden, Vanessa","orcid":"0000-0002-9438-4783","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Harald H.","last_name":"Sitte","full_name":"Sitte, Harald H."},{"last_name":"Janovjak","first_name":"Harald L","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315"}],"day":"15","title":"Isolation of synaptic vesicles from genetically engineered cultured neurons","external_id":{"pmid":["30496761"],"isi":["000456220900013"]},"status":"public","intvolume":" 312","citation":{"chicago":"Mckenzie, Catherine, Miroslava Spanova, Alexander J Johnson, Stephanie Kainrath, Vanessa Zheden, Harald H. Sitte, and Harald L Janovjak. “Isolation of Synaptic Vesicles from Genetically Engineered Cultured Neurons.” Journal of Neuroscience Methods. Elsevier, 2019. https://doi.org/10.1016/j.jneumeth.2018.11.018.","ieee":"C. Mckenzie et al., “Isolation of synaptic vesicles from genetically engineered cultured neurons,” Journal of Neuroscience Methods, vol. 312. Elsevier, pp. 114–121, 2019.","short":"C. Mckenzie, M. Spanova, A.J. Johnson, S. Kainrath, V. Zheden, H.H. Sitte, H.L. Janovjak, Journal of Neuroscience Methods 312 (2019) 114–121.","ama":"Mckenzie C, Spanova M, Johnson AJ, et al. Isolation of synaptic vesicles from genetically engineered cultured neurons. Journal of Neuroscience Methods. 2019;312:114-121. doi:10.1016/j.jneumeth.2018.11.018","apa":"Mckenzie, C., Spanova, M., Johnson, A. J., Kainrath, S., Zheden, V., Sitte, H. H., & Janovjak, H. L. (2019). Isolation of synaptic vesicles from genetically engineered cultured neurons. Journal of Neuroscience Methods. Elsevier. https://doi.org/10.1016/j.jneumeth.2018.11.018","mla":"Mckenzie, Catherine, et al. “Isolation of Synaptic Vesicles from Genetically Engineered Cultured Neurons.” Journal of Neuroscience Methods, vol. 312, Elsevier, 2019, pp. 114–21, doi:10.1016/j.jneumeth.2018.11.018.","ista":"Mckenzie C, Spanova M, Johnson AJ, Kainrath S, Zheden V, Sitte HH, Janovjak HL. 2019. Isolation of synaptic vesicles from genetically engineered cultured neurons. Journal of Neuroscience Methods. 312, 114–121."},"publication_status":"published","date_published":"2019-01-15T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"}],"year":"2019","_id":"7406","page":"114-121","type":"journal_article","month":"01","oa_version":"None","date_updated":"2023-09-06T15:27:29Z","abstract":[{"text":"Background\r\nSynaptic vesicles (SVs) are an integral part of the neurotransmission machinery, and isolation of SVs from their host neuron is necessary to reveal their most fundamental biochemical and functional properties in in vitro assays. Isolated SVs from neurons that have been genetically engineered, e.g. to introduce genetically encoded indicators, are not readily available but would permit new insights into SV structure and function. Furthermore, it is unclear if cultured neurons can provide sufficient starting material for SV isolation procedures.\r\n\r\nNew method\r\nHere, we demonstrate an efficient ex vivo procedure to obtain functional SVs from cultured rat cortical neurons after genetic engineering with a lentivirus.\r\n\r\nResults\r\nWe show that ∼108 plated cortical neurons allow isolation of suitable SV amounts for functional analysis and imaging. We found that SVs isolated from cultured neurons have neurotransmitter uptake comparable to that of SVs isolated from intact cortex. Using total internal reflection fluorescence (TIRF) microscopy, we visualized an exogenous SV-targeted marker protein and demonstrated the high efficiency of SV modification.\r\n\r\nComparison with existing methods\r\nObtaining SVs from genetically engineered neurons currently generally requires the availability of transgenic animals, which is constrained by technical (e.g. cost and time) and biological (e.g. developmental defects and lethality) limitations.\r\n\r\nConclusions\r\nThese results demonstrate the modification and isolation of functional SVs using cultured neurons and viral transduction. The ability to readily obtain SVs from genetically engineered neurons will permit linking in situ studies to in vitro experiments in a variety of genetic contexts.","lang":"eng"}],"volume":312,"date_created":"2020-01-30T09:12:19Z"},{"author":[{"first_name":"Daniel","last_name":"Capek","orcid":"0000-0001-5199-9940","id":"31C42484-F248-11E8-B48F-1D18A9856A87","full_name":"Capek, Daniel"},{"first_name":"Michael","last_name":"Smutny","full_name":"Smutny, Michael","orcid":"0000-0002-5920-9090","id":"3FE6E4E8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tichy","first_name":"Alexandra Madelaine","full_name":"Tichy, Alexandra Madelaine"},{"full_name":"Morri, Maurizio","id":"4863116E-F248-11E8-B48F-1D18A9856A87","first_name":"Maurizio","last_name":"Morri"},{"last_name":"Janovjak","first_name":"Harald L","full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg"}],"file":[{"file_id":"6041","date_updated":"2020-07-14T12:47:17Z","checksum":"6cb4ca6d4aa96f6f187a5983aa3e660a","date_created":"2019-02-18T15:17:21Z","access_level":"open_access","file_name":"2019_elife_Capek.pdf","file_size":5500707,"relation":"main_file","content_type":"application/pdf","creator":"dernst"}],"day":"06","title":"Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration","article_number":"e42093","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaHe"},{"_id":"HaJa"}],"publication":"eLife","article_processing_charge":"No","scopus_import":"1","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"doi":"10.7554/eLife.42093","quality_controlled":"1","project":[{"_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573"}],"isi":1,"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation."}],"date_updated":"2023-08-24T14:46:01Z","type":"journal_article","oa_version":"Published Version","month":"02","volume":8,"date_created":"2019-02-17T22:59:22Z","file_date_updated":"2020-07-14T12:47:17Z","year":"2019","_id":"6025","oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2019-02-06T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"external_id":{"isi":["000458025300001"]},"status":"public","intvolume":" 8","citation":{"ieee":"D. Capek, M. Smutny, A. M. Tichy, M. Morri, H. L. Janovjak, and C.-P. J. Heisenberg, “Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration,” eLife, vol. 8. eLife Sciences Publications, 2019.","chicago":"Capek, Daniel, Michael Smutny, Alexandra Madelaine Tichy, Maurizio Morri, Harald L Janovjak, and Carl-Philipp J Heisenberg. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42093.","short":"D. Capek, M. Smutny, A.M. Tichy, M. Morri, H.L. Janovjak, C.-P.J. Heisenberg, ELife 8 (2019).","ama":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. eLife. 2019;8. doi:10.7554/eLife.42093","ista":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. 2019. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. eLife. 8, e42093.","mla":"Capek, Daniel, et al. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” ELife, vol. 8, e42093, eLife Sciences Publications, 2019, doi:10.7554/eLife.42093.","apa":"Capek, D., Smutny, M., Tichy, A. M., Morri, M., Janovjak, H. L., & Heisenberg, C.-P. J. (2019). Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.42093"}},{"doi":"10.1016/j.jmb.2019.05.033","quality_controlled":"1","publication_identifier":{"eissn":["10898638"],"issn":["00222836"]},"isi":1,"language":[{"iso":"eng"}],"issue":"17","title":"Engineering strategy and vector library for the rapid generation of modular light-controlled protein–protein interactions","author":[{"full_name":"Tichy, Alexandra-Madelaine","id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87","first_name":"Alexandra-Madelaine","last_name":"Tichy"},{"first_name":"Elliot J.","last_name":"Gerrard","full_name":"Gerrard, Elliot J."},{"full_name":"Legrand, Julien M.D.","last_name":"Legrand","first_name":"Julien M.D."},{"full_name":"Hobbs, Robin M.","first_name":"Robin M.","last_name":"Hobbs"},{"id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L","last_name":"Janovjak","first_name":"Harald L"}],"day":"09","publication":"Journal of Molecular Biology","article_processing_charge":"No","scopus_import":"1","article_type":"original","publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"HaJa"}],"date_published":"2019-08-09T00:00:00Z","main_file_link":[{"open_access":"1","url":"http://www.biorxiv.org/content/10.1101/583369v1"}],"publication_status":"published","oa":1,"intvolume":" 431","citation":{"chicago":"Tichy, Alexandra-Madelaine, Elliot J. Gerrard, Julien M.D. Legrand, Robin M. Hobbs, and Harald L Janovjak. “Engineering Strategy and Vector Library for the Rapid Generation of Modular Light-Controlled Protein–Protein Interactions.” Journal of Molecular Biology. Elsevier, 2019. https://doi.org/10.1016/j.jmb.2019.05.033.","ieee":"A.-M. Tichy, E. J. Gerrard, J. M. D. Legrand, R. M. Hobbs, and H. L. Janovjak, “Engineering strategy and vector library for the rapid generation of modular light-controlled protein–protein interactions,” Journal of Molecular Biology, vol. 431, no. 17. Elsevier, pp. 3046–3055, 2019.","short":"A.-M. Tichy, E.J. Gerrard, J.M.D. Legrand, R.M. Hobbs, H.L. Janovjak, Journal of Molecular Biology 431 (2019) 3046–3055.","ama":"Tichy A-M, Gerrard EJ, Legrand JMD, Hobbs RM, Janovjak HL. Engineering strategy and vector library for the rapid generation of modular light-controlled protein–protein interactions. Journal of Molecular Biology. 2019;431(17):3046-3055. doi:10.1016/j.jmb.2019.05.033","apa":"Tichy, A.-M., Gerrard, E. J., Legrand, J. M. D., Hobbs, R. M., & Janovjak, H. L. (2019). Engineering strategy and vector library for the rapid generation of modular light-controlled protein–protein interactions. Journal of Molecular Biology. Elsevier. https://doi.org/10.1016/j.jmb.2019.05.033","ista":"Tichy A-M, Gerrard EJ, Legrand JMD, Hobbs RM, Janovjak HL. 2019. Engineering strategy and vector library for the rapid generation of modular light-controlled protein–protein interactions. Journal of Molecular Biology. 431(17), 3046–3055.","mla":"Tichy, Alexandra-Madelaine, et al. “Engineering Strategy and Vector Library for the Rapid Generation of Modular Light-Controlled Protein–Protein Interactions.” Journal of Molecular Biology, vol. 431, no. 17, Elsevier, 2019, pp. 3046–55, doi:10.1016/j.jmb.2019.05.033."},"external_id":{"isi":["000482872100002"]},"status":"public","volume":431,"date_created":"2019-06-16T21:59:14Z","page":"3046-3055","abstract":[{"lang":"eng","text":"Optogenetics enables the spatio-temporally precise control of cell and animal behavior. Many optogenetic tools are driven by light-controlled protein–protein interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying light-controlled PPIs to new target proteins is challenging because it is difficult to predict which of the many available LSDs, if any, will yield robust light regulation. As a consequence, fusion protein libraries need to be prepared and tested, but methods and platforms to facilitate this process are currently not available. Here, we developed a genetic engineering strategy and vector library for the rapid generation of light-controlled PPIs. The strategy permits fusing a target protein to multiple LSDs efficiently and in two orientations. The public and expandable library contains 29 vectors with blue, green or red light-responsive LSDs, many of which have been previously applied ex vivo and in vivo. We demonstrate the versatility of the approach and the necessity for sampling LSDs by generating light-activated caspase-9 (casp9) enzymes. Collectively, this work provides a new resource for optical regulation of a broad range of target proteins in cell and developmental biology."}],"date_updated":"2023-08-28T09:39:22Z","month":"08","type":"journal_article","oa_version":"Preprint","_id":"6564","year":"2019"},{"doi":"10.1038/s41467-018-04342-1","quality_controlled":"1","publication_identifier":{"issn":["2041-1723"]},"isi":1,"language":[{"iso":"eng"}],"issue":"1","project":[{"_id":"25548C20-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Microbial Ion Channels for Synthetic Neurobiology","grant_number":"303564"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"255A6082-B435-11E9-9278-68D0E5697425"}],"title":"Optical functionalization of human class A orphan G-protein-coupled receptors","article_number":"1950","author":[{"first_name":"Maurizio","last_name":"Morri","full_name":"Morri, Maurizio","id":"4863116E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sanchez-Romero, Inmaculada","id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87","last_name":"Sanchez-Romero","first_name":"Inmaculada"},{"id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87","full_name":"Tichy, Alexandra-Madelaine","first_name":"Alexandra-Madelaine","last_name":"Tichy"},{"id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","full_name":"Kainrath, Stephanie","first_name":"Stephanie","last_name":"Kainrath"},{"full_name":"Gerrard, Elliot J.","first_name":"Elliot J.","last_name":"Gerrard"},{"first_name":"Priscila","last_name":"Hirschfeld","full_name":"Hirschfeld, Priscila","id":"435ACB3A-F248-11E8-B48F-1D18A9856A87"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","first_name":"Jan","last_name":"Schwarz"},{"first_name":"Harald L","last_name":"Janovjak","full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"day":"01","file":[{"creator":"kschuh","content_type":"application/pdf","relation":"main_file","file_size":1349914,"file_name":"2018_Springer_Morri.pdf","access_level":"open_access","date_created":"2019-02-14T10:58:29Z","checksum":"8325fcc194264af4749e662a73bf66b5","date_updated":"2020-07-14T12:47:14Z","file_id":"5985"}],"publication":"Nature Communications","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Springer Nature","department":[{"_id":"HaJa"},{"_id":"CaGu"},{"_id":"MiSi"}],"date_published":"2018-12-01T00:00:00Z","ddc":["570"],"publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":" 9","citation":{"ista":"Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P, Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 9(1), 1950.","mla":"Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950, Springer Nature, 2018, doi:10.1038/s41467-018-04342-1.","apa":"Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J., Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-04342-1","ama":"Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-04342-1","short":"M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld, J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).","ieee":"M. Morri et al., “Optical functionalization of human class A orphan G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018.","chicago":"Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1."},"status":"public","external_id":{"isi":["000432280000006"]},"volume":9,"file_date_updated":"2020-07-14T12:47:14Z","date_created":"2019-02-14T10:50:24Z","abstract":[{"lang":"eng","text":"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."}],"date_updated":"2023-09-19T14:29:32Z","oa_version":"Published Version","month":"12","type":"journal_article","_id":"5984","year":"2018"},{"project":[{"grant_number":"RGY0084/2012","_id":"255BFFFA-B435-11E9-9278-68D0E5697425","name":"In situ real-time imaging of neurotransmitter signaling using designer optical sensors (HFSP Young Investigator)"}],"issue":"9","language":[{"iso":"eng"}],"isi":1,"quality_controlled":"1","doi":"10.1038/s41589-018-0108-2","department":[{"_id":"HaJa"}],"pmid":1,"publisher":"Nature Publishing Group","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_type":"original","article_processing_charge":"No","scopus_import":"1","publication":"Nature Chemical Biology","day":"30","author":[{"last_name":"Zhang","first_name":"William","full_name":"Zhang, William"},{"last_name":"Herde","first_name":"Michel","full_name":"Herde, Michel"},{"full_name":"Mitchell, Joshua","first_name":"Joshua","last_name":"Mitchell"},{"full_name":"Whitfield, Jason","first_name":"Jason","last_name":"Whitfield"},{"last_name":"Wulff","first_name":"Andreas","full_name":"Wulff, Andreas"},{"full_name":"Vongsouthi, Vanessa","first_name":"Vanessa","last_name":"Vongsouthi"},{"first_name":"Inmaculada","last_name":"Sanchez Romero","full_name":"Sanchez Romero, Inmaculada","id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Polina","last_name":"Gulakova","full_name":"Gulakova, Polina"},{"full_name":"Minge, Daniel","last_name":"Minge","first_name":"Daniel"},{"first_name":"Björn","last_name":"Breithausen","full_name":"Breithausen, Björn"},{"full_name":"Schoch, Susanne","first_name":"Susanne","last_name":"Schoch"},{"last_name":"Janovjak","first_name":"Harald L","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315"},{"last_name":"Jackson","first_name":"Colin","full_name":"Jackson, Colin"},{"full_name":"Henneberger, Christian","last_name":"Henneberger","first_name":"Christian"}],"publist_id":"7786","title":"Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS","status":"public","external_id":{"pmid":["30061718 "],"isi":["000442174500013"]},"citation":{"short":"W. Zhang, M. Herde, J. Mitchell, J. Whitfield, A. Wulff, V. Vongsouthi, I. Sanchez-Romero, P. Gulakova, D. Minge, B. Breithausen, S. Schoch, H.L. Janovjak, C. Jackson, C. Henneberger, Nature Chemical Biology 14 (2018) 861–869.","ieee":"W. Zhang et al., “Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS,” Nature Chemical Biology, vol. 14, no. 9. Nature Publishing Group, pp. 861–869, 2018.","chicago":"Zhang, William, Michel Herde, Joshua Mitchell, Jason Whitfield, Andreas Wulff, Vanessa Vongsouthi, Inmaculada Sanchez-Romero, et al. “Monitoring Hippocampal Glycine with the Computationally Designed Optical Sensor GlyFS.” Nature Chemical Biology. Nature Publishing Group, 2018. https://doi.org/10.1038/s41589-018-0108-2.","mla":"Zhang, William, et al. “Monitoring Hippocampal Glycine with the Computationally Designed Optical Sensor GlyFS.” Nature Chemical Biology, vol. 14, no. 9, Nature Publishing Group, 2018, pp. 861–69, doi:10.1038/s41589-018-0108-2.","ista":"Zhang W, Herde M, Mitchell J, Whitfield J, Wulff A, Vongsouthi V, Sanchez-Romero I, Gulakova P, Minge D, Breithausen B, Schoch S, Janovjak HL, Jackson C, Henneberger C. 2018. Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS. Nature Chemical Biology. 14(9), 861–869.","apa":"Zhang, W., Herde, M., Mitchell, J., Whitfield, J., Wulff, A., Vongsouthi, V., … Henneberger, C. (2018). Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS. Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/s41589-018-0108-2","ama":"Zhang W, Herde M, Mitchell J, et al. Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS. Nature Chemical Biology. 2018;14(9):861-869. doi:10.1038/s41589-018-0108-2"},"intvolume":" 14","oa":1,"publication_status":"published","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/30061718","open_access":"1"}],"date_published":"2018-07-30T00:00:00Z","year":"2018","_id":"137","type":"journal_article","month":"07","oa_version":"Submitted Version","date_updated":"2023-09-13T08:58:05Z","abstract":[{"lang":"eng","text":"Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-d-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli."}],"page":"861 - 869","date_created":"2018-12-11T11:44:49Z","volume":14},{"ddc":["571"],"date_published":"2017-05-20T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. Wiley. https://doi.org/10.1002/ange.201611998","ista":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. 129(16), 4679–4682.","mla":"Kainrath, Stephanie, et al. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” Angewandte Chemie, vol. 129, no. 16, Wiley, 2017, pp. 4679–82, doi:10.1002/ange.201611998.","ama":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. 2017;129(16):4679-4682. doi:10.1002/ange.201611998","short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie 129 (2017) 4679–4682.","chicago":"Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” Angewandte Chemie. Wiley, 2017. https://doi.org/10.1002/ange.201611998.","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen,” Angewandte Chemie, vol. 129, no. 16. Wiley, pp. 4679–4682, 2017."},"intvolume":" 129","status":"public","date_created":"2018-12-11T11:47:02Z","file_date_updated":"2020-07-14T12:46:39Z","volume":129,"abstract":[{"text":"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. ","lang":"ger"}],"date_updated":"2021-01-12T08:01:33Z","month":"05","oa_version":"Published Version","type":"journal_article","page":"4679 - 4682","_id":"538","year":"2017","quality_controlled":"1","doi":"10.1002/ange.201611998","pubrep_id":"932","language":[{"iso":"eng"}],"issue":"16","project":[{"call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","grant_number":"303564"},{"_id":"255A6082-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"}],"publist_id":"7279","title":"Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen","day":"20","file":[{"checksum":"d66fee867e7cdbfa3fe276c2fb0778bb","date_updated":"2020-07-14T12:46:39Z","file_id":"5007","access_level":"open_access","date_created":"2018-12-12T10:13:24Z","file_name":"IST-2018-932-v1+1_Kainrath_et_al-2017-Angewandte_Chemie.pdf","creator":"system","content_type":"application/pdf","relation":"main_file","file_size":1668557}],"author":[{"first_name":"Stephanie","last_name":"Kainrath","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","full_name":"Kainrath, Stephanie"},{"full_name":"Stadler, Manuela","first_name":"Manuela","last_name":"Stadler"},{"full_name":"Gschaider-Reichhart, Eva","orcid":"0000-0002-7218-7738","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","last_name":"Gschaider-Reichhart","first_name":"Eva"},{"full_name":"Distel, Martin","last_name":"Distel","first_name":"Martin"},{"first_name":"Harald L","last_name":"Janovjak","full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Angewandte Chemie","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"publisher":"Wiley","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"publist_id":"6451","title":"Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors","day":"15","author":[{"full_name":"Clifton, Ben","last_name":"Clifton","first_name":"Ben"},{"last_name":"Whitfield","first_name":"Jason","full_name":"Whitfield, Jason"},{"id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87","full_name":"Sanchez Romero, Inmaculada","last_name":"Sanchez Romero","first_name":"Inmaculada"},{"first_name":"Michel","last_name":"Herde","full_name":"Herde, Michel"},{"full_name":"Henneberger, Christian","last_name":"Henneberger","first_name":"Christian"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","last_name":"Janovjak","first_name":"Harald L"},{"last_name":"Jackson","first_name":"Colin","full_name":"Jackson, Colin"}],"scopus_import":1,"publication":"Synthetic Protein Switches","department":[{"_id":"HaJa"}],"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","publisher":"Springer","quality_controlled":"1","doi":"10.1007/978-1-4939-6940-1_5","publication_identifier":{"issn":["10643745"]},"language":[{"iso":"eng"}],"series_title":"Synthetic Protein Switches","project":[{"grant_number":"RGY0084/2012","_id":"255BFFFA-B435-11E9-9278-68D0E5697425","name":"In situ real-time imaging of neurotransmitter signaling using designer optical sensors (HFSP Young Investigator)"}],"date_created":"2018-12-11T11:49:24Z","volume":1596,"abstract":[{"lang":"eng","text":"Small molecule biosensors based on Forster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors."}],"date_updated":"2021-01-12T08:22:13Z","month":"03","type":"book_chapter","oa_version":"None","page":"71 - 87","_id":"957","year":"2017","date_published":"2017-03-15T00:00:00Z","publication_status":"published","citation":{"short":"B. Clifton, J. Whitfield, I. Sanchez-Romero, M. Herde, C. Henneberger, H.L. Janovjak, C. Jackson, in:, V. Stein (Ed.), Synthetic Protein Switches, Springer, 2017, pp. 71–87.","chicago":"Clifton, Ben, Jason Whitfield, Inmaculada Sanchez-Romero, Michel Herde, Christian Henneberger, Harald L Janovjak, and Colin Jackson. “Ancestral Protein Reconstruction and Circular Permutation for Improving the Stability and Dynamic Range of FRET Sensors.” In Synthetic Protein Switches, edited by Viktor Stein, 1596:71–87. Synthetic Protein Switches. Springer, 2017. https://doi.org/10.1007/978-1-4939-6940-1_5.","ieee":"B. Clifton et al., “Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors,” in Synthetic Protein Switches, vol. 1596, V. Stein, Ed. Springer, 2017, pp. 71–87.","apa":"Clifton, B., Whitfield, J., Sanchez-Romero, I., Herde, M., Henneberger, C., Janovjak, H. L., & Jackson, C. (2017). Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors. In V. Stein (Ed.), Synthetic Protein Switches (Vol. 1596, pp. 71–87). Springer. https://doi.org/10.1007/978-1-4939-6940-1_5","mla":"Clifton, Ben, et al. “Ancestral Protein Reconstruction and Circular Permutation for Improving the Stability and Dynamic Range of FRET Sensors.” Synthetic Protein Switches, edited by Viktor Stein, vol. 1596, Springer, 2017, pp. 71–87, doi:10.1007/978-1-4939-6940-1_5.","ista":"Clifton B, Whitfield J, Sanchez-Romero I, Herde M, Henneberger C, Janovjak HL, Jackson C. 2017.Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors. In: Synthetic Protein Switches. Methods in Molecular Biology, vol. 1596, 71–87.","ama":"Clifton B, Whitfield J, Sanchez-Romero I, et al. Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors. In: Stein V, ed. Synthetic Protein Switches. Vol 1596. Synthetic Protein Switches. Springer; 2017:71-87. doi:10.1007/978-1-4939-6940-1_5"},"intvolume":" 1596","editor":[{"full_name":"Stein, Viktor","last_name":"Stein","first_name":"Viktor"}],"status":"public","alternative_title":["Methods in Molecular Biology"]},{"volume":1596,"date_created":"2018-12-11T11:49:24Z","page":"89 - 99","oa_version":"None","type":"book_chapter","month":"05","abstract":[{"lang":"eng","text":"Biosensors that exploit Forster resonance energy transfer (FRET) can be used to visualize biological and physiological processes and are capable of providing detailed information in both spatial and temporal dimensions. In a FRET-based biosensor, substrate binding is associated with a change in the relative positions of two fluorophores, leading to a change in FRET efficiency that may be observed in the fluorescence spectrum. As a result, their design requires a ligand-binding protein that exhibits a conformational change upon binding. However, not all ligand-binding proteins produce responsive sensors upon conjugation to fluorescent proteins or dyes, and identifying the optimum locations for the fluorophores often involves labor-intensive iterative design or high-throughput screening. Combining the genetic fusion of a fluorescent protein to the ligand-binding protein with site-specific covalent attachment of a fluorescent dye can allow fine control over the positions of the two fluorophores, allowing the construction of very sensitive sensors. This relies upon the accurate prediction of the locations of the two fluorophores in bound and unbound states. In this chapter, we describe a method for computational identification of dye-attachment sites that allows the use of cysteine modification to attach synthetic dyes that can be paired with a fluorescent protein for the purposes of creating FRET sensors."}],"date_updated":"2021-01-12T08:22:13Z","_id":"958","year":"2017","date_published":"2017-05-15T00:00:00Z","publication_status":"published","intvolume":" 1596","citation":{"ama":"Mitchell J, Zhang W, Herde M, et al. Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment. In: Stein V, ed. Synthetic Protein Switches. Vol 1596. Synthetic Protein Switches. Springer; 2017:89-99. doi:10.1007/978-1-4939-6940-1_6","ista":"Mitchell J, Zhang W, Herde M, Henneberger C, Janovjak HL, O’Mara M, Jackson C. 2017.Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment. In: Synthetic Protein Switches. Methods in Molecular Biology, vol. 1596, 89–99.","mla":"Mitchell, Joshua, et al. “Method for Developing Optical Sensors Using a Synthetic Dye Fluorescent Protein FRET Pair and Computational Modeling and Assessment.” Synthetic Protein Switches, edited by Viktor Stein, vol. 1596, Springer, 2017, pp. 89–99, doi:10.1007/978-1-4939-6940-1_6.","apa":"Mitchell, J., Zhang, W., Herde, M., Henneberger, C., Janovjak, H. L., O’Mara, M., & Jackson, C. (2017). Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment. In V. Stein (Ed.), Synthetic Protein Switches (Vol. 1596, pp. 89–99). Springer. https://doi.org/10.1007/978-1-4939-6940-1_6","ieee":"J. Mitchell et al., “Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment,” in Synthetic Protein Switches, vol. 1596, V. Stein, Ed. Springer, 2017, pp. 89–99.","chicago":"Mitchell, Joshua, William Zhang, Michel Herde, Christian Henneberger, Harald L Janovjak, Megan O’Mara, and Colin Jackson. “Method for Developing Optical Sensors Using a Synthetic Dye Fluorescent Protein FRET Pair and Computational Modeling and Assessment.” In Synthetic Protein Switches, edited by Viktor Stein, 1596:89–99. Synthetic Protein Switches. Springer, 2017. https://doi.org/10.1007/978-1-4939-6940-1_6.","short":"J. Mitchell, W. Zhang, M. Herde, C. Henneberger, H.L. Janovjak, M. O’Mara, C. Jackson, in:, V. Stein (Ed.), Synthetic Protein Switches, Springer, 2017, pp. 89–99."},"alternative_title":["Methods in Molecular Biology"],"status":"public","editor":[{"first_name":"Viktor","last_name":"Stein","full_name":"Stein, Viktor"}],"title":"Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment","publist_id":"6450","author":[{"full_name":"Mitchell, Joshua","last_name":"Mitchell","first_name":"Joshua"},{"full_name":"Zhang, William","first_name":"William","last_name":"Zhang"},{"full_name":"Herde, Michel","first_name":"Michel","last_name":"Herde"},{"full_name":"Henneberger, Christian","first_name":"Christian","last_name":"Henneberger"},{"last_name":"Janovjak","first_name":"Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"},{"last_name":"O'Mara","first_name":"Megan","full_name":"O'Mara, Megan"},{"full_name":"Jackson, Colin","first_name":"Colin","last_name":"Jackson"}],"day":"15","publication":"Synthetic Protein Switches","scopus_import":1,"publisher":"Springer","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"HaJa"}],"doi":"10.1007/978-1-4939-6940-1_6","quality_controlled":"1","publication_identifier":{"issn":["10643745"]},"series_title":"Synthetic Protein Switches","language":[{"iso":"eng"}]},{"project":[{"grant_number":"RGY0084/2012","_id":"255BFFFA-B435-11E9-9278-68D0E5697425","name":"In situ real-time imaging of neurotransmitter signaling using designer optical sensors (HFSP Young Investigator)"},{"call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","grant_number":"303564"},{"grant_number":"W1232-B24","call_identifier":"FWF","_id":"255A6082-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"}],"language":[{"iso":"eng"}],"isi":1,"publication_identifier":{"issn":["09581669"]},"quality_controlled":"1","doi":"10.1016/j.copbio.2017.02.006","department":[{"_id":"HaJa"}],"publisher":"Elsevier","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_type":"original","article_processing_charge":"No","scopus_import":"1","ec_funded":1,"publication":"Current Opinion in Biotechnology","day":"01","author":[{"first_name":"Viviana","last_name":"Agus","full_name":"Agus, Viviana"},{"first_name":"Harald L","last_name":"Janovjak","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315"}],"publist_id":"6365","title":"Optogenetic methods in drug screening: Technologies and applications","external_id":{"isi":["000418313200003"]},"status":"public","citation":{"apa":"Agus, V., & Janovjak, H. L. (2017). Optogenetic methods in drug screening: Technologies and applications. Current Opinion in Biotechnology. Elsevier. https://doi.org/10.1016/j.copbio.2017.02.006","mla":"Agus, Viviana, and Harald L. Janovjak. “Optogenetic Methods in Drug Screening: Technologies and Applications.” Current Opinion in Biotechnology, vol. 48, Elsevier, 2017, pp. 8–14, doi:10.1016/j.copbio.2017.02.006.","ista":"Agus V, Janovjak HL. 2017. Optogenetic methods in drug screening: Technologies and applications. Current Opinion in Biotechnology. 48, 8–14.","ama":"Agus V, Janovjak HL. Optogenetic methods in drug screening: Technologies and applications. Current Opinion in Biotechnology. 2017;48:8-14. doi:10.1016/j.copbio.2017.02.006","short":"V. Agus, H.L. Janovjak, Current Opinion in Biotechnology 48 (2017) 8–14.","chicago":"Agus, Viviana, and Harald L Janovjak. “Optogenetic Methods in Drug Screening: Technologies and Applications.” Current Opinion in Biotechnology. Elsevier, 2017. https://doi.org/10.1016/j.copbio.2017.02.006.","ieee":"V. Agus and H. L. Janovjak, “Optogenetic methods in drug screening: Technologies and applications,” Current Opinion in Biotechnology, vol. 48. Elsevier, pp. 8–14, 2017."},"intvolume":" 48","publication_status":"published","date_published":"2017-12-01T00:00:00Z","year":"2017","acknowledgement":"This work was supported by grants of the European Union Seventh Framework Programme (CIG-303564), the Human Frontier Science Program (RGY0084_2012), and the Austrian Science Fund FWF (W1232 MolecularDrugTargets).","_id":"1026","month":"12","type":"journal_article","oa_version":"None","date_updated":"2023-09-22T09:26:06Z","abstract":[{"text":"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.","lang":"eng"}],"page":"8 - 14","date_created":"2018-12-11T11:49:45Z","volume":48},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","ec_funded":1,"article_processing_charge":"No","publication":"Angewandte Chemie - International Edition","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"publisher":"Wiley-Blackwell","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publist_id":"6362","title":"Green-light-induced inactivation of receptor signaling using cobalamin-binding domains","day":"20","file":[{"access_level":"open_access","date_created":"2019-01-18T09:39:55Z","date_updated":"2019-01-18T09:39:55Z","file_id":"5845","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":2614942,"success":1,"file_name":"2017_communications_Kainrath.pdf"}],"author":[{"full_name":"Kainrath, Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Kainrath"},{"full_name":"Stadler, Manuela","first_name":"Manuela","last_name":"Stadler"},{"last_name":"Gschaider-Reichhart","first_name":"Eva","full_name":"Gschaider-Reichhart, Eva","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7218-7738"},{"full_name":"Distel, Martin","last_name":"Distel","first_name":"Martin"},{"last_name":"Janovjak","first_name":"Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"}],"issue":"16","language":[{"iso":"eng"}],"isi":1,"project":[{"grant_number":"303564","name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets [do not use to be deleted]","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"quality_controlled":"1","doi":"10.1002/anie.201611998","publication_identifier":{"issn":["14337851"]},"_id":"1028","year":"2017","acknowledgement":"This work was supported by a grant from the European Union􏰝s Seventh Framework Programme (CIG-303564). E.R. was supported by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF), W1232) and a FemTech fellowship (Austrian Research Promotion Agency, 3580812)","date_created":"2018-12-11T11:49:46Z","file_date_updated":"2019-01-18T09:39:55Z","volume":56,"oa_version":"Published Version","month":"03","type":"journal_article","abstract":[{"text":"Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.","lang":"eng"}],"date_updated":"2024-03-25T23:30:08Z","page":"4608-4611","citation":{"short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie - International Edition 56 (2017) 4608–4611.","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Green-light-induced inactivation of receptor signaling using cobalamin-binding domains,” Angewandte Chemie - International Edition, vol. 56, no. 16. Wiley-Blackwell, pp. 4608–4611, 2017.","chicago":"Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition. Wiley-Blackwell, 2017. https://doi.org/10.1002/anie.201611998.","mla":"Kainrath, Stephanie, et al. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition, vol. 56, no. 16, Wiley-Blackwell, 2017, pp. 4608–11, doi:10.1002/anie.201611998.","ista":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 56(16), 4608–4611.","apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201611998","ama":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 2017;56(16):4608-4611. doi:10.1002/anie.201611998"},"intvolume":" 56","related_material":{"record":[{"relation":"dissertation_contains","id":"418","status":"public"},{"relation":"part_of_dissertation","id":"7680","status":"public"}]},"status":"public","external_id":{"isi":["000398154000038"]},"date_published":"2017-03-20T00:00:00Z","ddc":["540"],"has_accepted_license":"1","publication_status":"published","oa":1},{"volume":16,"date_created":"2018-12-11T11:50:08Z","file_date_updated":"2018-12-12T10:11:04Z","page":"866 - 877","oa_version":"Published Version","month":"07","type":"journal_article","date_updated":"2024-03-25T23:30:13Z","abstract":[{"lang":"eng","text":"During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation."}],"_id":"1100","acknowledgement":"We are grateful to members of the C.-P.H. and H.J. labs for discussions, R. Hauschild and the different Scientific Service Units at IST Austria for technical help, M. Dravecka for performing initial experiments, A. Schier for reading an earlier version of the manuscript, K.W. Rogers for technical help, and C. Hill, A. Bruce, and L. Solnica-Krezel for sending plasmids. This work was supported by grants from the Austrian Science Foundation (FWF): (T560-B17) and (I 812-B12) to V.R. and C.-P.H., and from the European Union (EU FP7): (6275) to H.J. A.I.-P. is supported by a Ramon Areces fellowship.","year":"2016","date_published":"2016-07-19T00:00:00Z","ddc":["570","576"],"acknowledged_ssus":[{"_id":"SSU"}],"oa":1,"publication_status":"published","has_accepted_license":"1","related_material":{"record":[{"status":"public","id":"961","relation":"dissertation_contains"},{"id":"50","status":"public","relation":"dissertation_contains"}]},"intvolume":" 16","citation":{"ama":"Sako K, Pradhan S, Barone V, et al. Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation. Cell Reports. 2016;16(3):866-877. doi:10.1016/j.celrep.2016.06.036","apa":"Sako, K., Pradhan, S., Barone, V., Inglés Prieto, Á., Mueller, P., Ruprecht, V., … Heisenberg, C.-P. J. (2016). Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.06.036","mla":"Sako, Keisuke, et al. “Optogenetic Control of Nodal Signaling Reveals a Temporal Pattern of Nodal Signaling Regulating Cell Fate Specification during Gastrulation.” Cell Reports, vol. 16, no. 3, Cell Press, 2016, pp. 866–77, doi:10.1016/j.celrep.2016.06.036.","ista":"Sako K, Pradhan S, Barone V, Inglés Prieto Á, Mueller P, Ruprecht V, Capek D, Galande S, Janovjak HL, Heisenberg C-PJ. 2016. Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation. Cell Reports. 16(3), 866–877.","chicago":"Sako, Keisuke, Saurabh Pradhan, Vanessa Barone, Álvaro Inglés Prieto, Patrick Mueller, Verena Ruprecht, Daniel Capek, Sanjeev Galande, Harald L Janovjak, and Carl-Philipp J Heisenberg. “Optogenetic Control of Nodal Signaling Reveals a Temporal Pattern of Nodal Signaling Regulating Cell Fate Specification during Gastrulation.” Cell Reports. Cell Press, 2016. https://doi.org/10.1016/j.celrep.2016.06.036.","ieee":"K. Sako et al., “Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation,” Cell Reports, vol. 16, no. 3. Cell Press, pp. 866–877, 2016.","short":"K. Sako, S. Pradhan, V. Barone, Á. Inglés Prieto, P. Mueller, V. Ruprecht, D. Capek, S. Galande, H.L. Janovjak, C.-P.J. Heisenberg, Cell Reports 16 (2016) 866–877."},"status":"public","title":"Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation","publist_id":"6275","author":[{"id":"3BED66BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6453-8075","full_name":"Sako, Keisuke","first_name":"Keisuke","last_name":"Sako"},{"first_name":"Saurabh","last_name":"Pradhan","full_name":"Pradhan, Saurabh"},{"full_name":"Barone, Vanessa","id":"419EECCC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2676-3367","last_name":"Barone","first_name":"Vanessa"},{"id":"2A9DB292-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5409-8571","full_name":"Inglés Prieto, Álvaro","last_name":"Inglés Prieto","first_name":"Álvaro"},{"last_name":"Mueller","first_name":"Patrick","full_name":"Mueller, Patrick"},{"first_name":"Verena","last_name":"Ruprecht","full_name":"Ruprecht, Verena","id":"4D71A03A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4088-8633"},{"first_name":"Daniel","last_name":"Capek","id":"31C42484-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5199-9940","full_name":"Capek, Daniel"},{"full_name":"Galande, Sanjeev","first_name":"Sanjeev","last_name":"Galande"},{"first_name":"Harald L","last_name":"Janovjak","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","full_name":"Janovjak, Harald L"},{"orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg"}],"file":[{"file_size":3921947,"relation":"main_file","content_type":"application/pdf","creator":"system","file_name":"IST-2017-754-v1+1_1-s2.0-S2211124716307768-main.pdf","date_created":"2018-12-12T10:11:04Z","access_level":"open_access","file_id":"4857","date_updated":"2018-12-12T10:11:04Z"}],"day":"19","publication":"Cell Reports","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":1,"ec_funded":1,"publisher":"Cell Press","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaHe"},{"_id":"HaJa"}],"doi":"10.1016/j.celrep.2016.06.036","quality_controlled":"1","pubrep_id":"754","issue":"3","language":[{"iso":"eng"}],"project":[{"name":"Cell- and Tissue Mechanics in Zebrafish Germ Layer Formation","call_identifier":"FWF","_id":"2529486C-B435-11E9-9278-68D0E5697425","grant_number":"T 560-B17"},{"_id":"2527D5CC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Cell Cortex and Germ Layer Formation in Zebrafish Gastrulation","grant_number":"I 812-B12"},{"call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","grant_number":"303564"}]},{"intvolume":" 1","citation":{"mla":"Mitchell, Joshua, et al. “Rangefinder: A Semisynthetic FRET Sensor Design Algorithm.” ACS SENSORS, vol. 1, no. 11, American Chemical Society, 2016, pp. 1286–90, doi:10.1021/acssensors.6b00576.","ista":"Mitchell J, Whitfield J, Zhang W, Henneberger C, Janovjak HL, O’Mara M, Jackson C. 2016. Rangefinder: A semisynthetic FRET sensor design algorithm. ACS SENSORS. 1(11), 1286–1290.","apa":"Mitchell, J., Whitfield, J., Zhang, W., Henneberger, C., Janovjak, H. L., O’Mara, M., & Jackson, C. (2016). Rangefinder: A semisynthetic FRET sensor design algorithm. ACS SENSORS. American Chemical Society. https://doi.org/10.1021/acssensors.6b00576","ama":"Mitchell J, Whitfield J, Zhang W, et al. Rangefinder: A semisynthetic FRET sensor design algorithm. ACS SENSORS. 2016;1(11):1286-1290. doi:10.1021/acssensors.6b00576","short":"J. Mitchell, J. Whitfield, W. Zhang, C. Henneberger, H.L. Janovjak, M. O’Mara, C. Jackson, ACS SENSORS 1 (2016) 1286–1290.","ieee":"J. Mitchell et al., “Rangefinder: A semisynthetic FRET sensor design algorithm,” ACS SENSORS, vol. 1, no. 11. American Chemical Society, pp. 1286–1290, 2016.","chicago":"Mitchell, Joshua, Jason Whitfield, William Zhang, Christian Henneberger, Harald L Janovjak, Megan O’Mara, and Colin Jackson. “Rangefinder: A Semisynthetic FRET Sensor Design Algorithm.” ACS SENSORS. American Chemical Society, 2016. https://doi.org/10.1021/acssensors.6b00576."},"language":[{"iso":"eng"}],"issue":"11","status":"public","doi":"10.1021/acssensors.6b00576","date_published":"2016-11-10T00:00:00Z","quality_controlled":"1","publication_status":"published","publication":"ACS SENSORS","_id":"1101","scopus_import":"1","article_processing_charge":"No","publisher":"American Chemical Society","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","acknowledgement":"J.A.M., J.H.W., and W.H.Z. were supported by Australian\r\nPostgraduate Awards (APA), AS Sargeson Supplementary\r\nscholarships, and RSC supplementary scholarships. C.J.J.\r\nacknowledges support from a Human Frontiers in Science\r\nYoung Investigator Award and a Discovery Project and Future\r\nFellowship from the Australian Research Council. M.L.O. is\r\nsupported by an Australian Research Council Discovery Project\r\n(DP130102153) and the Merit Allocation Scheme of the\r\nNational Computational Infrastructure.","year":"2016","department":[{"_id":"HaJa"}],"title":"Rangefinder: A semisynthetic FRET sensor design algorithm","volume":1,"date_created":"2018-12-11T11:50:09Z","publist_id":"6274","author":[{"last_name":"Mitchell","first_name":"Joshua","full_name":"Mitchell, Joshua"},{"first_name":"Jason","last_name":"Whitfield","full_name":"Whitfield, Jason"},{"first_name":"William","last_name":"Zhang","full_name":"Zhang, William"},{"first_name":"Christian","last_name":"Henneberger","full_name":"Henneberger, Christian"},{"id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L","first_name":"Harald L","last_name":"Janovjak"},{"first_name":"Megan","last_name":"O'Mara","full_name":"O'Mara, Megan"},{"full_name":"Jackson, Colin","first_name":"Colin","last_name":"Jackson"}],"page":"1286 - 1290","date_updated":"2023-03-30T11:32:33Z","day":"10","abstract":[{"lang":"eng","text":"Optical sensors based on the phenomenon of Förster resonance energy transfer (FRET) are powerful tools that have advanced the study of small molecules in biological systems. However, sensor construction is not trivial and often requires multiple rounds of engineering or an ability to screen large numbers of variants. A method that would allow the accurate rational design of FRET sensors would expedite the production of biologically useful sensors. Here, we present Rangefinder, a computational algorithm that allows rapid in silico screening of dye attachment sites in a ligand-binding protein for the conjugation of a dye molecule to act as a Förster acceptor for a fused fluorescent protein. We present three ratiometric fluorescent sensors designed with Rangefinder, including a maltose sensor with a dynamic range of >300% and the first sensors for the most abundant sialic acid in human cells, N-acetylneuraminic acid. Provided a ligand-binding protein exists, it is our expectation that this model will facilitate the design of an optical sensor for any small molecule of interest."}],"month":"11","type":"journal_article","oa_version":"None"},{"title":"Light at the end of the protein: Crystal structure of a C-terminal light-sensing domain","volume":24,"date_created":"2018-12-11T11:52:02Z","publist_id":"5756","page":"213 - 215","author":[{"full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","first_name":"Harald L","last_name":"Janovjak"}],"type":"journal_article","oa_version":"None","month":"02","date_updated":"2021-01-12T06:50:46Z","day":"02","_id":"1440","publication":"Structure","ec_funded":1,"scopus_import":1,"acknowledgement":"The author thanks Banerjee et al. (2016) for providing coordinates prior to public release and apologizes to colleagues whose work was not cited or discussed due to the limited space available. The author is supported by grants from EU FP7 (CIG-303564), HFSP (RGY0084_2012), and FWF (W1232).","publisher":"Cell Press","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"HaJa"}],"year":"2016","doi":"10.1016/j.str.2016.01.002","date_published":"2016-02-02T00:00:00Z","quality_controlled":"1","publication_status":"published","intvolume":" 24","issue":"2","language":[{"iso":"eng"}],"citation":{"short":"H.L. Janovjak, Structure 24 (2016) 213–215.","ieee":"H. L. Janovjak, “Light at the end of the protein: Crystal structure of a C-terminal light-sensing domain,” Structure, vol. 24, no. 2. Cell Press, pp. 213–215, 2016.","chicago":"Janovjak, Harald L. “Light at the End of the Protein: Crystal Structure of a C-Terminal Light-Sensing Domain.” Structure. Cell Press, 2016. https://doi.org/10.1016/j.str.2016.01.002.","ista":"Janovjak HL. 2016. Light at the end of the protein: Crystal structure of a C-terminal light-sensing domain. Structure. 24(2), 213–215.","mla":"Janovjak, Harald L. “Light at the End of the Protein: Crystal Structure of a C-Terminal Light-Sensing Domain.” Structure, vol. 24, no. 2, Cell Press, 2016, pp. 213–15, doi:10.1016/j.str.2016.01.002.","apa":"Janovjak, H. L. (2016). Light at the end of the protein: Crystal structure of a C-terminal light-sensing domain. Structure. Cell Press. https://doi.org/10.1016/j.str.2016.01.002","ama":"Janovjak HL. Light at the end of the protein: Crystal structure of a C-terminal light-sensing domain. Structure. 2016;24(2):213-215. doi:10.1016/j.str.2016.01.002"},"project":[{"grant_number":"RGY0084/2012","_id":"255BFFFA-B435-11E9-9278-68D0E5697425","name":"In situ real-time imaging of neurotransmitter signaling using designer optical sensors (HFSP Young Investigator)"},{"call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","grant_number":"303564"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"255A6082-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"status":"public"},{"quality_controlled":"1","doi":"10.1002/anie.201601736","pubrep_id":"840","language":[{"iso":"eng"}],"issue":"21","project":[{"name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","grant_number":"303564"},{"_id":"255A6082-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"}],"publist_id":"5755","title":"A phytochrome sensory domain permits receptor activation by red light","day":"17","file":[{"file_name":"IST-2017-840-v1+1_reichhart.pdf","creator":"system","relation":"main_file","content_type":"application/pdf","file_size":1268662,"checksum":"26da07960e57ac4750b54179197ce57f","date_updated":"2020-07-14T12:44:55Z","file_id":"5255","access_level":"open_access","date_created":"2018-12-12T10:17:03Z"}],"author":[{"full_name":"Gschaider-Reichhart, Eva","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7218-7738","last_name":"Gschaider-Reichhart","first_name":"Eva"},{"last_name":"Inglés Prieto","first_name":"Álvaro","id":"2A9DB292-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5409-8571","full_name":"Inglés Prieto, Álvaro"},{"id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87","full_name":"Tichy, Alexandra-Madelaine","first_name":"Alexandra-Madelaine","last_name":"Tichy"},{"last_name":"Mckenzie","first_name":"Catherine","full_name":"Mckenzie, Catherine","id":"3EEDE19A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L","last_name":"Janovjak"}],"scopus_import":1,"ec_funded":1,"publication":"Angewandte Chemie - International Edition","department":[{"_id":"HaJa"}],"publisher":"Wiley","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2016-05-17T00:00:00Z","ddc":["571","576"],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"ista":"Gschaider-Reichhart E, Inglés Prieto Á, Tichy A-M, Mckenzie C, Janovjak HL. 2016. A phytochrome sensory domain permits receptor activation by red light. Angewandte Chemie - International Edition. 55(21), 6339–6342.","mla":"Gschaider-Reichhart, Eva, et al. “A Phytochrome Sensory Domain Permits Receptor Activation by Red Light.” Angewandte Chemie - International Edition, vol. 55, no. 21, Wiley, 2016, pp. 6339–42, doi:10.1002/anie.201601736.","apa":"Gschaider-Reichhart, E., Inglés Prieto, Á., Tichy, A.-M., Mckenzie, C., & Janovjak, H. L. (2016). A phytochrome sensory domain permits receptor activation by red light. Angewandte Chemie - International Edition. Wiley. https://doi.org/10.1002/anie.201601736","ama":"Gschaider-Reichhart E, Inglés Prieto Á, Tichy A-M, Mckenzie C, Janovjak HL. A phytochrome sensory domain permits receptor activation by red light. Angewandte Chemie - International Edition. 2016;55(21):6339-6342. doi:10.1002/anie.201601736","short":"E. Gschaider-Reichhart, Á. Inglés Prieto, A.-M. Tichy, C. Mckenzie, H.L. Janovjak, Angewandte Chemie - International Edition 55 (2016) 6339–6342.","ieee":"E. Gschaider-Reichhart, Á. Inglés Prieto, A.-M. Tichy, C. Mckenzie, and H. L. Janovjak, “A phytochrome sensory domain permits receptor activation by red light,” Angewandte Chemie - International Edition, vol. 55, no. 21. Wiley, pp. 6339–6342, 2016.","chicago":"Gschaider-Reichhart, Eva, Álvaro Inglés Prieto, Alexandra-Madelaine Tichy, Catherine Mckenzie, and Harald L Janovjak. “A Phytochrome Sensory Domain Permits Receptor Activation by Red Light.” Angewandte Chemie - International Edition. Wiley, 2016. https://doi.org/10.1002/anie.201601736."},"related_material":{"record":[{"relation":"dissertation_contains","id":"418","status":"public"}]},"intvolume":" 55","status":"public","file_date_updated":"2020-07-14T12:44:55Z","date_created":"2018-12-11T11:52:02Z","volume":55,"abstract":[{"text":"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.","lang":"eng"}],"date_updated":"2023-09-07T12:49:08Z","type":"journal_article","month":"05","oa_version":"Submitted Version","page":"6339 - 6342","_id":"1441","year":"2016","acknowledgement":"A.I.-P. was supported by a Ramon Areces fellowship, and E.R. by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF): W1232) and a FemTech fellowship (Austrian Research Promotion Agency: 3580812)."},{"doi":"10.1038/nchembio.1933","quality_controlled":"1","pubrep_id":"837","language":[{"iso":"eng"}],"issue":"12","project":[{"grant_number":"303564","name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425"},{"name":"In situ real-time imaging of neurotransmitter signaling using designer optical sensors (HFSP Young Investigator)","_id":"255BFFFA-B435-11E9-9278-68D0E5697425","grant_number":"RGY0084/2012"},{"grant_number":"W1232-B24","_id":"255A6082-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"}],"title":"Light-assisted small-molecule screening against protein kinases","publist_id":"5471","author":[{"last_name":"Inglés Prieto","first_name":"Álvaro","full_name":"Inglés Prieto, Álvaro","orcid":"0000-0002-5409-8571","id":"2A9DB292-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7218-7738","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","full_name":"Gschaider-Reichhart, Eva","last_name":"Gschaider-Reichhart","first_name":"Eva"},{"full_name":"Muellner, Markus","last_name":"Muellner","first_name":"Markus"},{"first_name":"Matthias","last_name":"Nowak","full_name":"Nowak, Matthias","id":"30845DAA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Nijman","first_name":"Sebastian","full_name":"Nijman, Sebastian"},{"first_name":"Michael","last_name":"Grusch","full_name":"Grusch, Michael"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","last_name":"Janovjak","first_name":"Harald L"}],"day":"12","file":[{"checksum":"e9fb251dfcb7cd209b83f17867e61321","file_id":"4842","date_updated":"2020-07-14T12:45:12Z","access_level":"open_access","date_created":"2018-12-12T10:10:51Z","file_name":"IST-2017-837-v1+1_ingles-prieto.pdf","creator":"system","file_size":1308364,"content_type":"application/pdf","relation":"main_file"}],"publication":"Nature Chemical Biology","ec_funded":1,"scopus_import":1,"publisher":"Nature Publishing Group","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"HaJa"},{"_id":"LifeSc"}],"ddc":["571"],"date_published":"2015-10-12T00:00:00Z","publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":" 11","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"418"}]},"citation":{"ama":"Inglés Prieto Á, Gschaider-Reichhart E, Muellner M, et al. Light-assisted small-molecule screening against protein kinases. Nature Chemical Biology. 2015;11(12):952-954. doi:10.1038/nchembio.1933","apa":"Inglés Prieto, Á., Gschaider-Reichhart, E., Muellner, M., Nowak, M., Nijman, S., Grusch, M., & Janovjak, H. L. (2015). Light-assisted small-molecule screening against protein kinases. Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.1933","ista":"Inglés Prieto Á, Gschaider-Reichhart E, Muellner M, Nowak M, Nijman S, Grusch M, Janovjak HL. 2015. Light-assisted small-molecule screening against protein kinases. Nature Chemical Biology. 11(12), 952–954.","mla":"Inglés Prieto, Álvaro, et al. “Light-Assisted Small-Molecule Screening against Protein Kinases.” Nature Chemical Biology, vol. 11, no. 12, Nature Publishing Group, 2015, pp. 952–54, doi:10.1038/nchembio.1933.","chicago":"Inglés Prieto, Álvaro, Eva Gschaider-Reichhart, Markus Muellner, Matthias Nowak, Sebastian Nijman, Michael Grusch, and Harald L Janovjak. “Light-Assisted Small-Molecule Screening against Protein Kinases.” Nature Chemical Biology. Nature Publishing Group, 2015. https://doi.org/10.1038/nchembio.1933.","ieee":"Á. Inglés Prieto et al., “Light-assisted small-molecule screening against protein kinases,” Nature Chemical Biology, vol. 11, no. 12. Nature Publishing Group, pp. 952–954, 2015.","short":"Á. Inglés Prieto, E. Gschaider-Reichhart, M. Muellner, M. Nowak, S. Nijman, M. Grusch, H.L. Janovjak, Nature Chemical Biology 11 (2015) 952–954."},"status":"public","volume":11,"date_created":"2018-12-11T11:53:25Z","file_date_updated":"2020-07-14T12:45:12Z","page":"952 - 954","abstract":[{"text":"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.","lang":"eng"}],"date_updated":"2023-09-07T12:49:09Z","month":"10","oa_version":"Submitted Version","type":"journal_article","_id":"1678","acknowledgement":"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).","year":"2015"},{"_id":"1867","year":"2015","date_created":"2018-12-11T11:54:26Z","volume":36,"month":"02","type":"journal_article","oa_version":"None","abstract":[{"lang":"eng","text":"Cultured mammalian cells essential are model systems in basic biology research, production platforms of proteins for medical use, and testbeds in synthetic biology. Flavin cofactors, in particular flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are critical for cellular redox reactions and sense light in naturally occurring photoreceptors and optogenetic tools. Here, we quantified flavin contents of commonly used mammalian cell lines. We first compared three procedures for extraction of free and noncovalently protein-bound flavins and verified extraction using fluorescence spectroscopy. For separation, two CE methods with different BGEs were established, and detection was performed by LED-induced fluorescence with limit of detections (LODs 0.5-3.8 nM). We found that riboflavin (RF), FMN, and FAD contents varied significantly between cell lines. RF (3.1-14 amol/cell) and FAD (2.2-17.0 amol/cell) were the predominant flavins, while FMN (0.46-3.4 amol/cell) was found at markedly lower levels. Observed flavin contents agree with those previously extracted from mammalian tissues, yet reduced forms of RF were detected that were not described previously. Quantification of flavins in mammalian cell lines will allow a better understanding of cellular redox reactions and optogenetic tools."}],"date_updated":"2021-01-12T06:53:43Z","page":"518 - 525","citation":{"ama":"Hühner J, Inglés Prieto Á, Neusüß C, Lämmerhofer M, Janovjak HL. Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection. Electrophoresis. 2015;36(4):518-525. doi:10.1002/elps.201400451","apa":"Hühner, J., Inglés Prieto, Á., Neusüß, C., Lämmerhofer, M., & Janovjak, H. L. (2015). Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection. Electrophoresis. Wiley. https://doi.org/10.1002/elps.201400451","mla":"Hühner, Jens, et al. “Quantification of Riboflavin, Flavin Mononucleotide, and Flavin Adenine Dinucleotide in Mammalian Model Cells by CE with LED-Induced Fluorescence Detection.” Electrophoresis, vol. 36, no. 4, Wiley, 2015, pp. 518–25, doi:10.1002/elps.201400451.","ista":"Hühner J, Inglés Prieto Á, Neusüß C, Lämmerhofer M, Janovjak HL. 2015. Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection. Electrophoresis. 36(4), 518–525.","chicago":"Hühner, Jens, Álvaro Inglés Prieto, Christian Neusüß, Michael Lämmerhofer, and Harald L Janovjak. “Quantification of Riboflavin, Flavin Mononucleotide, and Flavin Adenine Dinucleotide in Mammalian Model Cells by CE with LED-Induced Fluorescence Detection.” Electrophoresis. Wiley, 2015. https://doi.org/10.1002/elps.201400451.","ieee":"J. Hühner, Á. Inglés Prieto, C. Neusüß, M. Lämmerhofer, and H. L. Janovjak, “Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection,” Electrophoresis, vol. 36, no. 4. Wiley, pp. 518–525, 2015.","short":"J. Hühner, Á. Inglés Prieto, C. Neusüß, M. Lämmerhofer, H.L. Janovjak, Electrophoresis 36 (2015) 518–525."},"intvolume":" 36","status":"public","date_published":"2015-02-01T00:00:00Z","publication_status":"published","scopus_import":1,"ec_funded":1,"publication":"Electrophoresis","department":[{"_id":"HaJa"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Wiley","publist_id":"5230","title":"Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection","day":"01","author":[{"full_name":"Hühner, Jens","first_name":"Jens","last_name":"Hühner"},{"last_name":"Inglés Prieto","first_name":"Álvaro","orcid":"0000-0002-5409-8571","id":"2A9DB292-F248-11E8-B48F-1D18A9856A87","full_name":"Inglés Prieto, Álvaro"},{"first_name":"Christian","last_name":"Neusüß","full_name":"Neusüß, Christian"},{"full_name":"Lämmerhofer, Michael","first_name":"Michael","last_name":"Lämmerhofer"},{"last_name":"Janovjak","first_name":"Harald L","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315"}],"issue":"4","language":[{"iso":"eng"}],"project":[{"call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","grant_number":"303564"},{"_id":"255BFFFA-B435-11E9-9278-68D0E5697425","name":"In situ real-time imaging of neurotransmitter signaling using designer optical sensors (HFSP Young Investigator)","grant_number":"RGY0084/2012"}],"quality_controlled":"1","doi":"10.1002/elps.201400451","pubrep_id":"836"}]