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ChemBioAP SIGNED

Elucidation of autophagy using novel chemical probes

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EC-Contrib. €

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Partnership

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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 SE (UMEA) coordinator 1˙414˙550.00
2    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) participant 85˙449.00

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 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

year authors and title journal last update
List of publications.
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, Yao‐Wen Wu
Light‐Induced Dimerization Approaches to Control Cellular Processes
published pages: 12452-12463, ISSN: 0947-6539, DOI: 10.1002/chem.201900562
Chemistry – 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 Schölermann, Mridula Dwivedi, Lei Li, Pablo Rios-Munoz, Maja Köhn, 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 Müller, Sarah Zinken, Thomas Pinkert, Julian Wilke, Dale Corkery, Axel Pahl, Sonja Sievers, Petra Janning, Christoph Arenz, Yaowen Wu, Raphaël 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. Carnero Corrales, Georgios Konstantinidis, Makoto Muroi, André 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
“Molecular Activity Painting”: 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 Rätz, Matthias Röger, Yao-Wen Wu
Spatial Cycling of Rab GTPase, Driven by the GTPase Cycle, Controls Rab’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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