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POLICE SIGNED

The PIDDosome in Centrosome and Ploidy-Surveillance

Total Cost €

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EC-Contrib. €

0

Partnership

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 POLICE project word cloud

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

underlying    protease    mitotic    health    pole    disease    segregation    hepatocytes    puts    machineries    proteolysis    ageing    fundamental    body    centrosome    piddosome    nor    inhibitor    function    cycle    cancer    interface    controls    position    regenerative    demonstrated    poorly    immunity    efforts    regeneration    suppressor    inflammation    deregulated    series    cells    mammalian    medicine    cardiomyocytes    premature    therapeutic    ploidy    accumulation    activated    organogenesis    human    alerting    normal    lines    polices    tolerance    structures    mdm2    accompanied    mediated    relevance    family    ciliogenesis    regulator    meet    carry    integrative    tight    nucleating    cytokinesis    inactivating    organismal    aneuploidy    cell    extra    interfering    p53    balanced    death    proper    notably    errors    proliferating    pathologies    diploid    causing    fusion    sterile    chromosome    centrosomes    police    organ    spindle    polyploidization    caspase    tumor   

Project "POLICE" data sheet

The following table provides information about the project.

Coordinator
MEDIZINISCHE UNIVERSITAT INNSBRUCK 

Organization address
address: CHRISTOPH PROBST PLATZ 1
city: INNSBRUCK
postcode: 6020
website: www.i-med.ac.at

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 Austria [AT]
 Total cost 2˙355˙000 €
 EC max contribution 2˙355˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-10-01   to  2023-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MEDIZINISCHE UNIVERSITAT INNSBRUCK AT (INNSBRUCK) coordinator 2˙355˙000.00

Map

 Project objective

Tight control of the number of chromosome sets in a cell (ploidy) is fundamental for normal development and organismal health. Most cells in our body are diploid, yet, some cells, including cardiomyocytes or hepatocytes require a balanced increase in ploidy for proper function. Polyploidization is accompanied by an accumulation of centrosomes, structures needed for nucleating the mitotic spindle and ciliogenesis. Extra centrosomes, however, promote aneuploidy in proliferating cells by causing errors in chromosome segregation, underlying a series of human pathologies, most notably cancer and premature ageing. How polyploidization is controlled in organogenesis and how errors in ploidy control contribute to disease is poorly understood. We recently demonstrated that the “PIDDosome” complex polices centrosome numbers in mammalian cells, alerting the tumor suppressor p53 in response to extra centrosomes. This is achieved by inactivating MDM2, the key-inhibitor of p53, by targeted proteolysis. MDM2-processing is mediated by caspase-2, a neglected member in a protease family that controls cell death and inflammation, activated in the PIDDosome. This exciting finding allows examining the consequences of deregulated ploidy and centrosome number in development and disease without interfering with p53, nor the cell fusion or cytokinesis machineries. This puts us in pole position to carry out an integrative study that aims to develop the PIDDosome as a new therapeutic target in cancer, related inflammation and in regenerative medicine. To meet this aim, we will define (i) the relevance of the PIDDosome in aneuploidy tolerance of cancer (ii) the role of the PIDDosome in controlling sterile inflammation and immunity (iii) the PIDDosome as a key-regulator of organ development and regeneration POLICE will open new lines of research at the interface of cell cycle, cell death & inflammation control and promote the PIDDosome as new target in our efforts to improve human health.

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The information about "POLICE" are provided by the European Opendata Portal: CORDIS opendata.

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