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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.

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

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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