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MECHANOCHECK

ATR-mediated mechanotransduction and connections with the actin cytoskeleton

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 MECHANOCHECK project word cloud

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

atomic    found    quantitatively    functional    stress    association    dna    cope    suggest    barrier    ddr    associates    atr    exhibit    damage    expression    protects    molecular    nucleus    systematically    protein    explore    questions    micropatterned    occurs    substrate    actin    kinase    relevance    act    prevents    foiani    mechanical    hypothesis    multidisciplinary    device    microscopy    modulation    unclear    osmotic    nuclear    chk1    extracellular    mediated    condensation    cellular    aberrant    cancer    cytoskeleton    laboratory    atm    fragile    controls    stimuli    techniques    anti    force    cell    breakdown    transitions    connections    genes    linking    microenvironment    forms    integrity    site    chromosomes    mechanosensing    prophase    microfluidic    mutated    accompanied    chromatin    primarily    plasticity    envelope    employ    events    biology    chk2    prompted    afm    observations    topological    mechanism    cells    defective    oncogenic    replicating    mechanotransduction   

Project "MECHANOCHECK" data sheet

The following table provides information about the project.

Coordinator
IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE 

Organization address
address: VIA ADAMELLO 16
city: MILANO
postcode: 20139
website: www.ifom-firc.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 180˙277 €
 EC max contribution 180˙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-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2018-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE IT (MILANO) coordinator 180˙277.00

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 Project objective

The ATR protein kinase controls the DNA damage response (DDR), with ATM, Chk1 and Chk2. DDR genes are often mutated in cancer cells and act as an anti-cancer barrier in response to oncogenic stimuli. ATR is essential and protects the integrity of replicating chromosomes, prevents fragile site expression and aberrant condensation events. The Foiani laboratory recently found that ATR associates with the nuclear envelope during S phase and prophase and in response to osmotic or mechanical stress. Moreover, ATR-defective cells exhibit aberrant chromatin condensation and nuclear envelope breakdown. These observations prompted us to suggest that the ATR-mediated mechanical response enables cells to cope with the mechanical stress induced by topological transitions through the modulation of nuclear plasticity and chromatin association to the nuclear envelope. However, the molecular mechanism and functional relevance of ATR-mediated mechanical response remain unclear. Mechanosensing occurs primarily through the actin cytoskeleton, which forms the cellular mechanical system linking the extracellular microenvironment to the nucleus. We aim at understanding the connections between the ATR-mediated mechanotransduction pathway and actin modulation in response to mechanical stress. Our working hypothesis is that ATR may be part of an integrated response to mechanical stress that has a more general role in controlling cell and nuclear plasticity through the modulation of actin cytoskeleton and nuclear events. To address these questions, we will employ and develop various multidisciplinary approaches including state-of-the-art Atomic Force Microscopy (AFM), micropatterned protein substrate, novel microfluidic device and accompanied with advanced molecular biology techniques in order to quantitatively and systematically explore the ATR mediated mechanotransduction.

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