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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.

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

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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