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NeuroInCellNMR SIGNED

In-cell NMR monitoring of alpha-Synuclein aggregation in neuronal cells

Total Cost €

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EC-Contrib. €

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Partnership

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Project "NeuroInCellNMR" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

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 Israel [IL]
 Total cost 1˙996˙500 €
 EC max contribution 1˙996˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 1˙143˙821.00
2    FORSCHUNGSVERBUND BERLIN EV DE (BERLIN) participant 852˙678.00

Map

 Project objective

Intracellular aggregation of the human amyloid protein alpha-synuclein is causally involved in Parkinson’s disease, a debilitating neurodegenerative disorder. The goal of this project is to combine low-resolution, fluorescence-imaging methods with high-resolution in-cell NMR and EPR spectroscopy techniques to derive macroscopic and microscopic insights into alpha-synuclein aggregate structures directly in neuronal cells.

To achieve this goal, we will employ different sets of cultured neurons and investigate intracellular alpha-synuclein aggregation under defined conditions of mitochondrial dysfunction and cellular oxidative stress, two of the most common denominators of the disease. Importantly, we will also establish a human stem cell model for studying alpha-synuclein aggregation with high-resolution in-cell NMR and EPR methods, by using induced pluripotent stem cell (iPSC) derived dopaminergic neurons from Parkinson’s disease patients and control individuals.

Results from this study will provide novel insights into the native mechanisms of intracellular aggregate formation and ultimately enable novel pharmacological approaches for therapeutic intervention.

 Publications

year authors and title journal last update
List of publications.
2016 Thomas Müntener, Daniel Häussinger, Philipp Selenko, Francois-Xavier Theillet
In-Cell Protein Structures from 2D NMR Experiments
published pages: 2821-2825, ISSN: 1948-7185, DOI: 10.1021/acs.jpclett.6b01074
The Journal of Physical Chemistry Letters 7/14 2019-07-25
2016 A. Mylona, F.-X. Theillet, C. Foster, T. M. Cheng, F. Miralles, P. A. Bates, P. Selenko, R. Treisman
Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation
published pages: 233-237, ISSN: 0036-8075, DOI: 10.1126/science.aad1872
Science 354/6309 2019-07-25
2016 Andres Binolfi, Antonio Limatola, Silvia Verzini, Jonas Kosten, Francois-Xavier Theillet, Honor May Rose, Beata Bekei, Marchel Stuiver, Marleen van Rossum, Philipp Selenko
Intracellular repair of oxidation-damaged α-synuclein fails to target C-terminal modification sites
published pages: 10251, ISSN: 2041-1723, DOI: 10.1038/ncomms10251
Nature Communications 7 2019-07-25
2017 Jürgen M Plitzko, Benjamin Schuler, Philipp Selenko
Structural Biology outside the box — inside the cell
published pages: 110-121, ISSN: 0959-440X, DOI: 10.1016/j.sbi.2017.06.007
Current Opinion in Structural Biology 46 2019-07-25
2018 Gavin Young, Nikolas Hundt, Daniel Cole, Adam Fineberg, Joanna Andrecka, Andrew Tyler, Anna Olerinyova, Ayla Ansari, Erik G. Marklund, Miranda P. Collier, Shane A. Chandler, Olga Tkachenko, Joel Allen, Max Crispin, Neil Billington, Yasuharu Takagi, James R. Sellers, Cédric Eichmann, Philipp Selenko, Lukas Frey, Roland Riek, Martin R. Galpin, Weston B. Struwe, Justin L. P. Benesch, Philipp Kukura
Quantitative mass imaging of single biological macromolecules
published pages: 423-427, ISSN: 0036-8075, DOI: 10.1126/science.aar5839
Science 360/6387 2019-07-25
2016 Francois-Xavier Theillet, Andres Binolfi, Beata Bekei, Andrea Martorana, Honor May Rose, Marchel Stuiver, Silvia Verzini, Dorothea Lorenz, Marleen van Rossum, Daniella Goldfarb, Philipp Selenko
Structural disorder of monomeric α-synuclein persists in mammalian cells
published pages: 45-50, ISSN: 0028-0836, DOI: 10.1038/nature16531
Nature 530/7588 2019-07-25

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