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YAP MECHANO SIGNED

Elucidating the mechanism of mechanotransduction through YAP and TAZ

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 YAP MECHANO project word cloud

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

therapy    environment    optogenetic    fate    gene    act    regulate    uncovering    remodeling    cancer    forces    hippo    molecular    network    cell    instructing    despite    nuclear    shuttling    plan    experiencing    pioneered    rapid    crucially    laboratory    death    tension    players    cells    aid    elusive    yap    function    actomyosin    implementing    outer    cellular    link    actin    progression    cytoskeletal    deeply    biochemical    generality    mechanical    taz    gain    mass    tissue    newly    gap    tools    translocation    functional    derive    coactivators    delineate    subjected    behavior    validation    sufficient    mechanics    model    mechanistic    mechanosensing    piccolo    mechanotransduction    cytoskeleton    stiffening    influence    inputs    systematically    activate    activation    experiments    driving    proliferation    homeostasis    genetic    events    cues    strain    view    regulation    interaction    notion    tumour    transcriptional    probe    dynamics    live    close    effectors    remained    spectrometry    independently    imaging    expression    components    biology   

Project "YAP MECHANO" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI PADOVA 

Organization address
address: VIA 8 FEBBRAIO 2
city: PADOVA
postcode: 35122
website: www.unipd.it

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 Italy [IT]
 Total cost 168˙277 €
 EC max contribution 168˙277 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI PADOVA IT (PADOVA) coordinator 168˙277.00

Map

 Project objective

The mechanical properties of the cellular environment deeply influence cell fate and behavior. Cells respond to outer forces not only through the rapid remodeling of their cytoskeleton, but also by implementing gene expression changes. The Piccolo laboratory pioneered the notion that the transcriptional coactivators YAP and TAZ act independently of the Hippo pathway to activate gene expression in response to cytoskeletal tension. Crucially, YAP/TAZ are the main effectors of the cellular response to mechanical cues instructing proliferation, cell death or cell fate choice. Despite the importance of mechanosensing in development, tissue homeostasis and cancer, the mechanistic link between the actin network and YAP/ TAZ regulation has remained elusive. This project aims to close this gap in our knowledge by uncovering the molecular events that lead to the activation and nuclear translocation of YAP/TAZ in cells experiencing mechanical strain. Using live imaging, I plan to derive a model of the nuclear YAP shuttling dynamics. Optogenetic tools and targeted genetic approaches will be used to delineate which components of the actomyosin network are sufficient to regulate YAP/TAZ and to probe a potential link to nuclear mechanics. Mass spectrometry will provide a comprehensive view of YAP/TAZ interaction partners in cells subjected to different mechanical inputs and biochemical validation experiments will systematically delineate the molecular pathway of mechanotransduction from cytoskeletal tension to YAP/TAZ activation. Finally, loss- and gain-of-function experiments in a range of model systems will establish the functional importance and generality of these newly identified mechanotransduction pathway players. Uncovering the mechanotransduction pathway will not only greatly advance our understanding of cell biology, but also aid to identify potential targets for cancer therapy, as indeed the stiffening of the tumour environment is a driving factor in cancer progression.

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