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SiGNATURE SIGNED

Selection of human iPSC-derived cardiomyocytes by sinGle cell geNe expression and pAtch clamp for a maTUre caRdiac modEl

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 SiGNATURE project word cloud

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

precisely    replace    correlating    genetic    gene    combining    reveal    academic    autonomous    hipsc    conventional    unexpected    maturation    good    cardiomyocyte    functionally    understand    inter    diseases    discovery    underlying    mechanisms    caused    line    cms    chemotherapeutics    candidates    splice    host    whom    phenotypes    drugs    immature    genes    imprinted    markers    interdisciplinary    variability    incidence    pluripotent    stem    preferably    molecular    lines    rates    cardiac    safety    ethnic    sufficient    human    disease    cardiomyocytes    drug    gender    expression    arrhythmias    animal    view    private    screening    individual    phenotype    share    validated    lab    first    contributions    aging    expressed    limiting    least    simultaneously    proof    3d    single    postnatally    genome    function    cell    variant    signature    cm    electrophysiology    personalized    electrical    expertise    preclinical    mature    recapitulate    suitable    adult    selecting    culture    models    evident    outcome    presently   

Project "SiGNATURE" data sheet

The following table provides information about the project.

Coordinator
ACADEMISCH ZIEKENHUIS LEIDEN 

Organization address
address: ALBINUSDREEF 2
city: LEIDEN
postcode: 2333 ZA
website: www.lumc.nl

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 Netherlands [NL]
 Total cost 187˙572 €
 EC max contribution 187˙572 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2020
 Duration (year-month-day) from 2020-02-01   to  2022-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ACADEMISCH ZIEKENHUIS LEIDEN NL (LEIDEN) coordinator 187˙572.00

Map

 Project objective

The incidence of cardiac arrhythmias in Europe is increasing because of aging and unexpected side effects of drugs, such as chemotherapeutics. To understand mechanisms underlying these conditions requires reliable preferably human models. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are presently good candidates since they share the genome of the individual from whom they are derived and can thus recapitulate genetic, ethnic and gender contributions to the cardiac disease phenotypes. However, their immature state and high inter- and intra-line variability is limiting their value as preclinical models. In the proposed project, I will address these issues through an interdisciplinary approach combining a unique 3D culture maturation system developed in my host lab with my expertise in electrophysiology. I will characterize gene expression and electrical properties of single cardiomyocytes simultaneously with view to directly correlating genes with function and identify molecular markers associated with the functionally mature cardiac phenotype. Two genetic cardiac diseases (one caused by an imprinted gene, the other by a postnatally expressed splice variant) for which the host already has hiPSC lines, will be used as proof of concept that hiPSC-CM maturation in this system is sufficient (i) to reveal disease phenotypes not evident in conventional culture and (ii) to identify molecular markers suitable for selecting mature hiPSC-CMs for drug testing. Overall, this project will provide the first functionally-relevant gene signature of (mature) hiPSC-CMs, and thus be an important advance in modelling all cardiomyocyte autonomous cardiac diseases more precisely for (personalized) drug screening. The outcome will be available to academic and private researchers to enhance rates of drug discovery and safety, and promote hiPSC-CMs as validated adult cardiac models to replace, at least in part, the use of animal models.

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

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