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GUIDESIGINT

Competitive assembly dynamics of the DCC receptor with its guidance cues integrates signals for cellular steering

Total Cost €

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EC-Contrib. €

0

Partnership

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 GUIDESIGINT project word cloud

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

assaying    receptors    events    cell    multivalent    translation    colorectal    integration    indicates    guide    assemblies    human    death    secreted    sources    vessel    binding    signaling    neurons    formed    proteins    multicellular    neighboring    describe    programmed    examine    communication    insights    experimentally    networks    dynamic    membrane    connectivity    endothelial    thereby    physiological    appropriate    dependent    dynamics    assembly    receptor    proper    turning    elicit    hub    away    poised    cellular    living    medically    biophysical    organisms    form    deleted    efforts    draxin    exchange    guidance    simulated    multiple    action    simulations    mechanism    therapeutic    experiments    biological    distance    tissue    validated    underlie    migration    brain    orientation    interactions    transmembrane    netrin    source    dcc    blood    misprogramming    computationally    cues    placed    mechanistic    intervention    unprecedented    tumorigenesis    organization    polarized    basis    complemented    integrates    beads    signal    ing    soaked    cancer    competitive    axons    inputs    cells   

Project "GUIDESIGINT" data sheet

The following table provides information about the project.

Coordinator
EUROPEAN MOLECULAR BIOLOGY LABORATORY 

Organization address
address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117
website: http://www.embl.de

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 Germany [DE]
 Project website http://www.embl-hamburg.de/research/unit/meijers/index.html
 Total cost 159˙460 €
 EC max contribution 159˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-02-01   to  2019-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EUROPEAN MOLECULAR BIOLOGY LABORATORY DE (HEIDELBERG) coordinator 159˙460.00

Map

 Project objective

Secreted proteins and their receptors underlie the communication networks of multicellular organisms and guide the proper organization of developing tissue. An essential process involves the human transmembrane receptor and signal integration hub, Deleted in Colorectal Cancer (DCC). Emerging evidence indicates that the netrin and draxin guidance cues are secreted by neighboring cells and form competitive and complex multivalent interactions with DCC. The DCC receptor thus integrates multiple inputs (netrin and draxin) to elicit the appropriate physiological response (cell migration towards or away from the source of netrin or draxin, or even programmed cell death), resulting in proper connectivity of neurons in the brain and of endothelial cells in blood vessel networks, or their misprogramming in tumorigenesis. Our knowledge of this medically important signaling pathway is now poised for translation to an integrated systems mechanism across biological scale. This research action will address the challenge by experimentally determining the competitive and multivalent assemblies formed among netrin, draxin and DCC as a biophysical basis for signal integration. These binding events will then be computationally simulated to examine their dynamic partner exchange and polarized orientation of assemblies in the membrane that are dependent on their distance from the netrin and draxin sources. Experiments and simulations of competitive binding and assembly will be further complemented and validated by assaying the distance-dependent turning response of living axons placed between netrin and draxin-soaked beads. Together, these approaches will describe the competitive assembly dynamics of signaling and will provide unprecedented mechanistic insights into cellular communication and organization, thereby targeting efforts for therapeutic intervention.

 Publications

year authors and title journal last update
List of publications.
2018 Robert G. Smock, Rob Meijers
Roles of glycosaminoglycans as regulators of ligand/receptor complexes
published pages: 180026, ISSN: 2046-2441, DOI: 10.1098/rsob.180026
Open Biology 8/10 2019-08-30
2017 Lorenzo I. Finci, Jie Zhang, Xiaqin Sun, Robert G. Smock, Rob Meijers, Yan Zhang, Junyu Xiao, Jia-huai Wang
Structure of unliganded membrane-proximal domains FN4-FN5-FN6 of DCC
published pages: 701-705, ISSN: 1674-800X, DOI: 10.1007/s13238-017-0439-x
Protein & Cell 8/9 2019-08-30

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