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ChemBioAP SIGNED

Elucidation of autophagy using novel chemical probes

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

ChemBioAP project word cloud

Explore the words cloud of the ChemBioAP project. It provides you a very rough idea of what is the project "ChemBioAP" about.

fide suited first chemical bona caged lc3 proteins herein cancer dynamic questions lipidated genes realize delipidation marker monitor elucidate protein cid last prepare enormously termed model elusive evolutionarily cell chronic synthetic eukaryotes establishment function temporal intend autophagosome knock manipulation biological plan confer structure off despite pi3k endogenous phenotypic neurodegenerative probes functions disorders thereby reveal versatile chemically followed dimerization autophagy avenue genetic renders strategy extensive semi mechanism diseases reversible conserved complexes lipidation dynamics tool biogenesis

Project "ChemBioAP" data sheet

The following table provides information about the project.

Coordinator	UMEA UNIVERSITET Organization address address: UNIVERSITETOMRADET city: UMEA postcode: 901 87 website: www.umu.se contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Sweden [SE]
Total cost	1˙500˙000 €
EC max contribution	1˙500˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2015-STG
Funding Scheme	ERC-STG
Starting year	2016
Duration (year-month-day)	from 2016-09-01 to 2021-08-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UMEA UNIVERSITET UMEA UNIVERSITET Organization address address: UNIVERSITETOMRADET city: UMEA postcode: 901 87 website: www.umu.se contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SE (UMEA)	coordinator	1˙414˙550.00
2	MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Organization address address: HOFGARTENSTRASSE 8 city: MUENCHEN postcode: 80539 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (MUENCHEN)	participant	85˙449.00

Map

Project objective

The interest on autophagy, an evolutionarily conserved process in eukaryotes, has enormously increased in the last years, since autophagy is involved in many diseases such as cancer and neurodegenerative disorders. Autophagosome formation is the key process in autophagy. Despite extensive work, the model of autophagosome formation is not yet well established. Some important questions on autophagosome biogenesis remain to be elusive, such as where the bona fide marker protein of autophagosome, LC3, is lipidated, how lipidated LC3 functions in autophagosome formation, and how the proteins for LC3 lipidation and delipidation are involved in autophagosome formation. Although genetic approaches have been useful to identify genes involved in autophagy, they are chronic and thereby the dynamics of phenotypic change cannot be followed, making them not suited for study highly dynamic process such as autophagosome formation. Herein, I propose to develop and use novel chemical probes to address these issues. First, I plan to prepare semi-synthetic caged LC3 proteins and apply them to monitor dynamics of autophagosome formation in the cell in order to address those questions on autophagosome formation. The semi-synthetic LC3 proteins are expected to confer a temporal control and to realize manipulation of protein structure, which renders such studies possible. Second, I intend to develop a versatile approach targeting specific endogenous proteins using a reversible chemically induced dimerization (CID) system, termed as “knock on and off” strategy. I plan to use this approach to elucidate the function of two distinct PI3K complexes in autophagosome formation. On one hand, the establishment of novel approaches will open up a new avenue for studying biological processes. On the other hand, the use of the tool will reveal the mechanism of autophagy.

Publications

List of publications.
year	authors and title	journal	last update
2020	Fang-Yi Li, Zhen-Feng Zhang, Stephanie Voss, Yao-Wen Wu, Yu-Fen Zhao, Yan-Mei Li, Yong-Xiang Chen Inhibition of K-Ras4B-plasma membrane association with a membrane microdomain-targeting peptide published pages: 826-832, ISSN: 2041-6520, DOI: 10.1039/c9sc04726c	Chemical Science 11/3	2020-02-28
2019	Laura Klewer, Yaoâ€Wen Wu Lightâ€Induced Dimerization Approaches to Control Cellular Processes published pages: 12452-12463, ISSN: 0947-6539, DOI: 10.1002/chem.201900562	Chemistry â€“ A European Journal 25/54	2020-02-28
2019	Luca Laraia, Alexandra Friese, Dale P. Corkery, Georgios Konstantinidis, Nelli Erwin, Walter Hofer, Hacer Karatas, Laura Klewer, Andreas Brockmeyer, Malte Metz, Beate SchÃ¶lermann, Mridula Dwivedi, Lei Li, Pablo Rios-Munoz, Maja KÃ¶hn, Roland Winter, Ingrid R. Vetter, Slava Ziegler, Petra Janning, Yao-Wen Wu, Herbert Waldmann The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis published pages: 710-720, ISSN: 1552-4450, DOI: 10.1038/s41589-019-0307-5	Nature Chemical Biology 15/7	2020-02-28
2019	Amal Alex, Valentina Piano, Soumitra Polley, Marchel Stuiver, Stephanie Voss, Giuseppe Ciossani, Katharina Overlack, Beate Voss, Sabine Wohlgemuth, Arsen Petrovic, Yaowen Wu, Philipp Selenko, Andrea Musacchio, Stefano Maffini Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.48287	eLife 8	2020-02-28
2019	Yao-Wen Wu, Herbert Waldmann Toward the role of cholesterol and cholesterol transfer protein in autophagosome biogenesis published pages: 2167-2168, ISSN: 1554-8627, DOI: 10.1080/15548627.2019.1666595	Autophagy 15/12	2020-02-28
2019	Luca Laraia, Guillaume Garivet, Daniel J. Foley, Nadine Kaiser, Sebastian MÃ¼ller, Sarah Zinken, Thomas Pinkert, Julian Wilke, Dale Corkery, Axel Pahl, Sonja Sievers, Petra Janning, Christoph Arenz, Yaowen Wu, RaphaÃ«l Rodriguez, Herbert Waldmann Image-Based Morphological Profiling Identifies a Lysosomotropic, Iron-Sequestering Autophagy Inhibitor published pages: , ISSN: 1433-7851, DOI: 10.1002/anie.201913712	Angewandte Chemie International Edition	2020-02-28
2019	Yao-Wen Wu, Fu Li Bacterial interaction with host autophagy published pages: 352-362, ISSN: 2150-5594, DOI: 10.1080/21505594.2019.1602020	Virulence 10/1	2020-02-28
2017	Luca Laraia, Kosuke Ohsawa, Georgios Konstantinidis, Lucas Robke, Yao-Wen Wu, Kamal Kumar, Herbert Waldmann Discovery of Novel Cinchona-Alkaloid-Inspired Oxazatwistane Autophagy Inhibitors published pages: 2145-2150, ISSN: 1433-7851, DOI: 10.1002/anie.201611670	Angewandte Chemie International Edition 56/8	2019-06-19
2017	Lucas Robke, Luca Laraia, Marjorie A. Carneroâ€…Corrales, Georgios Konstantinidis, Makoto Muroi, AndrÃ© Richters, Michael Winzker, Tobias Engbring, Stefano Tomassi, Nobumoto Watanabe, Hiroyuki Osada, Daniel Rauh, Herbert Waldmann, Yao-Wen Wu, Julian Engel Phenotypic Identification of a Novel Autophagy Inhibitor Chemotype Targeting Lipid Kinase VPS34 published pages: 8153-8157, ISSN: 1433-7851, DOI: 10.1002/anie.201703738	Angewandte Chemie International Edition 56/28	2019-06-19
2017	Xi Chen, Muthukumaran Venkatachalapathy, Dominic Kamps, Simone Weigel, Ravi Kumar, Michael Orlich, Ruben Garrecht, Michael Hirtz, Christof M. Niemeyer, Yao-Wen Wu, Leif Dehmelt â€œMolecular Activity Paintingâ€: Switch-like, Light-Controlled Perturbations inside Living Cells published pages: 5916-5920, ISSN: 1433-7851, DOI: 10.1002/anie.201611432	Angewandte Chemie International Edition 56/21	2019-06-19
2018	Lucas Robke, Yushi Futamura, Georgios Konstantinidis, Julian Wilke, Harumi Aono, Zhwan Mahmoud, Nobumoto Watanabe, Yao-Wen Wu, Hiroyuki Osada, Luca Laraia, Herbert Waldmann Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex I published pages: 3014-3022, ISSN: 2041-6520, DOI: 10.1039/c7sc05040b	Chemical Science 9/11	2019-06-19
2017	Supansa Pantoom, Aimin Yang, Yao-Wen Wu Lift and cut: Anti-host autophagy mechanism of Legionella pneumophila published pages: 1467-1469, ISSN: 1554-8627, DOI: 10.1080/15548627.2017.1327943	Autophagy 13/8	2019-06-19
2017	Aimin Yang, Supansa Pantoom, Yao-Wen Wu Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.23905	eLife 6	2019-06-19
2017	Aimin Yang, Inken Hacheney, Yao-Wen Wu Semisynthesis of autophagy protein LC3 conjugates published pages: 4971-4976, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2017.05.051	Bioorganic & Medicinal Chemistry 25/18	2019-06-19
2018	Xi Chen, Yao-Wen Wu Tunable and Photoswitchable Chemically Induced Dimerization for Chemo-optogenetic Control of Protein and Organelle Positioning published pages: 6796-6799, ISSN: 1433-7851, DOI: 10.1002/anie.201800140	Angewandte Chemie International Edition 57/23	2019-06-19
2019	Nadine Kaiser, Dale Corkery, Yaowen Wu, Luca Laraia, Herbert Waldmann Modulation of autophagy by the novel mitochondrial complex I inhibitor Authipyrin published pages: , ISSN: 0968-0896, DOI: 10.1016/j.bmc.2019.02.028	Bioorganic & Medicinal Chemistry	2019-05-09
2019	Stephanie Voss, Fu Li, Andreas RÃ¤tz, Matthias RÃ¶ger, Yao-Wen Wu Spatial Cycling of Rab GTPase, Driven by the GTPase Cycle, Controls Rabâ€™s Subcellular Distribution published pages: 276-285, ISSN: 0006-2960, DOI: 10.1021/acs.biochem.8b00932	Biochemistry 58/4	2019-05-09
2018	Xi Chen, Muthukumaran Venkatachalapathy, Leif Dehmelt, Yao-Wen Wu Multidirectional Activity Control of Cellular Processes by a Versatile Chemo-optogenetic Approach published pages: 11993-11997, ISSN: 1433-7851, DOI: 10.1002/anie.201806976	Angewandte Chemie International Edition 57/37	2019-05-09

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