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MAIN SIGNED

Molecular Adhesion and Interactions in the Nervous system

Total Cost €

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EC-Contrib. €

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Partnership

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Project "MAIN" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITEIT UTRECHT 

Organization address
address: HEIDELBERGLAAN 8
city: UTRECHT
postcode: 3584 CS
website: www.uu.nl

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 Netherlands [NL]
 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 2016-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT UTRECHT NL (UTRECHT) coordinator 1˙500˙000.00

Map

 Project objective

Surface-attached proteins establish cell-to-cell contacts and generate signals to control development and function of tissues. It is not clear how protein structure and interactions organize into intercellular assemblies to regulate signalling and adhesion. Using a hybrid approach and focusing on two cell-signalling systems critical for nervous system function, I will determine how protein conformation, interaction and spatial arrangement form cis and trans assemblies to control intercellular adhesion and signalling.

In the mammalian nervous system where intricate intercellular connections are highly abundant, two protein interaction systems play essential roles and have been studied extensively on a cellular and in vivo level: 1. Notch receptors with Jagged and Delta-like ligands in neurogenesis and neuronal plasticity 2. Contactins with Casprs, Neurofascin and Amyloid Precursor Protein in formation and maintenance of the nervous system. In addition, Notch signalling triggered by Contactins promotes cell maturation and interlinks these two signalling systems. The detailed molecular-level structures and interactions, however, remain largely unresolved and, consequently, our understanding of how Notch and Contactin conformational and oligomeric changes trigger cell signalling and adhesion is limited.

The overall aim is to resolve the extracellular interactions of adhesion and the molecular mechanisms underlying signalling in the Notch and Contactin systems.

I will combine X-ray crystallography and cryo-EM to determine structures of proteins, complexes and higher-order assemblies in the pre- and post-intercellular state, and use biophysical and cellular methods to probe cis and trans multivalent interactions. This will provide the molecular basis of intercellular communication and a stepping stone for the development of therapeutics to treat Notch and Contactin associated neurological disorders and cancers.

 Publications

year authors and title journal last update
List of publications.
2019 Hedwich C. Vlieg, Eric G. Huizinga, Bert J. C. Janssen
Structure and flexibility of the extracellular region of the PirB receptor
published pages: 4634-4643, ISSN: 0021-9258, DOI: 10.1074/jbc.ra118.004396
Journal of Biological Chemistry 294/12 2019-05-27
2018 Nadia Leloup, Lucas M. P. Chataigner, Bert J. C. Janssen
Structural insights into SorCS2–Nerve Growth Factor complex formation
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05405-z
Nature Communications 9/1 2019-05-29

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The information about "MAIN" are provided by the European Opendata Portal: CORDIS opendata.

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