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MECHEMGUI SIGNED

The integration of mechanical and chemical signals in neuronal guidance

Total Cost €

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EC-Contrib. €

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Partnership

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 MECHEMGUI project word cloud

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

dynamics    combining    tissue    arrangements    extend    engineering    alterations    put    signalling    requested    guide    shed    cns    regulate    developmental    paths    puzzle    during    gap    time    pathfinding    distant    discovery    re    nervous    predictive    central    patterns    integrate    mechanisms    environment    pi    unknown    mechanosensitive    close    cues    framework    modulating    predict    mechanical    complete    physics    start    missing    damaged    attractive    inducing    suggesting    proper    axon    axonal    efficient    regeneration    story    biomedical    vitro    crowded    computational    axons    outgrowth    motility    poorly    local    isa    neurons    model    1st    evident    stiffness    molecular    signaling    ultimately    commitments    indirectly    guidance    vivo    signals    cascades    activated    repulsive    neuronal    brain    place    mechanically    biochemical    june    chemical    date    light    modulate    cellular    comprehension    2018    first    biology    breakthrough    mechanotransduction    cytoskeletal   

Project "MECHEMGUI" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

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 United Kingdom [UK]
 Total cost 2˙468˙520 €
 EC max contribution 2˙468˙520 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-06-01   to  2023-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 2˙468˙520.00

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 Project objective

During the development of the central nervous system (CNS), neurons extend axons through a crowded environment along well-defined pathways to reach their distant targets. It isA start date of 1st June 2018 is being requested to enable the PI to complete a number of current commitments and put the necessary arrangements in place to enable an efficient start up phase of the project. evident that attractive and repulsive guidance cues in the tissue provide important biochemical signals to guide growing axons along their paths. This can only be part of the story, however, as it is still not possible to predict axonal growth patterns in vivo. In a recent breakthrough discovery, we provided in vivo evidence that neurons also respond to mechanical cues, such as local tissue stiffness, suggesting that mechanical signals are likely an important missing part of the puzzle. However, mechanically activated signaling pathways are currently poorly understood, and how neurons integrate mechanical and chemical signals to result in proper outgrowth is unknown.

By investigating how mechanical signals control neuronal growth and pathfinding, this proposal will close this comprehension gap. By combining state-of-the-art approaches in physics, engineering and biology, we will, for the first time, identify mechanosensitive molecular mechanisms that regulate neuronal growth and guidance in vitro and in vivo. In particular, we will investigate how mechanotransduction cascades (1) directly modulate axon growth by inducing local changes in cytoskeletal dynamics, and (2) indirectly lead to alterations in axon outgrowth by modulating chemical signalling pathways. Ultimately, we will develop a computational model based on our findings, which will lead to a predictive framework for understanding axon pathfinding in the developing brain.

The proposed research challenges current concepts in developmental biology and is very relevant to many other areas in biology. Our results will not only shed new light on the complex control mechanisms of cellular growth and motility, but could also lead to novel biomedical approaches aimed at facilitating neuronal re-growth and regeneration in the damaged CNS.

 Publications

year authors and title journal last update
List of publications.
2019 Yassen Abbas, Alejandro Carnicer-Lombarte, Lucy Gardner, Jake Thomas, Jan J Brosens, Ashley Moffett, Andrew M Sharkey, Kristian Franze, Graham J Burton, Michelle L Oyen
Tissue stiffness at the human maternal–fetal interface
published pages: 1999-2008, ISSN: 0268-1161, DOI: 10.1093/humrep/dez139
Human Reproduction 34/10 2020-02-05
2019 Maximilian AH Jakobs, Andrea Dimitracopoulos, Kristian Franze
KymoButler, a deep learning software for automated kymograph analysis
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.42288
eLife 8 2020-02-05
2019 Michael Segel, Björn Neumann, Myfanwy F. E. Hill, Isabell P. Weber, Carlo Viscomi, Chao Zhao, Adam Young, Chibeza C. Agley, Amelia J. Thompson, Ginez A. Gonzalez, Amar Sharma, Staffan Holmqvist, David H. Rowitch, Kristian Franze, Robin J. M. Franklin, Kevin J. Chalut
Niche stiffness underlies the ageing of central nervous system progenitor cells
published pages: 130-134, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1484-9
Nature 573/7772 2020-02-05
2019 Amelia J Thompson, Eva K Pillai, Ivan B Dimov, Sarah K Foster, Christine E Holt, Kristian Franze
Rapid changes in tissue mechanics regulate cell behaviour in the developing embryonic brain
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.39356
eLife 8 2020-01-23

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