Opendata, web and dolomites

HD-DittoGraph SIGNED

HD-DittoGraph: a digital human Embryonic Stem Cell platform for Huntington's repeats

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 HD-DittoGraph project word cloud

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

causative    pure    instability    candidate    sequences    neurogenic    validated    novelty    insights    expansion    repeat    huntington    neurons    intend    networks    generating    human    simultaneous    individually    barcoded    contribution    couples    length    postmitotic    lof    computational    stem    transcriptome    cis    generation    divisions    unequivocally    function    gof    ad    neuronal    sequence    multiple    sgrnas    mitotic    unstable    huntingtin    hes    inducible    disease    perform    differentiating    functional    modifiers    embryonic    act    barcodes    platforms    striatal    screenings    genes    thousands    htt    exon    trans    acting    corresponding    dividing    crispr    causing    genome    gain    genetic    platform    flanking    cag    donor    cell    cells    cas9    shaped    subsequently    mechanisms    constructs    gene    pipelines    relies    screen    introduce    identification    modifier    size    libraries    construction    sequencing    hoc    molecular    efficient    locus    tested    library    association   

Project "HD-DittoGraph" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI MILANO 

Organization address
address: Via Festa Del Perdono 7
city: MILANO
postcode: 20122
website: www.unimi.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 2˙040˙943 €
 EC max contribution 2˙040˙943 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-03-01   to  2023-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI MILANO IT (MILANO) coordinator 1˙868˙443.00
2    FONDAZIONE ISTITUTO NAZIONALE DI GENETICA MOLECOLARE INGM IT (MILANO) participant 172˙500.00

Map

 Project objective

This proposal is aimed at identifying the molecular mechanisms that have brought the human Huntington Disease-causing Huntingtin (Htt) exon 1, with its pure and unstable CAG repeat, to be shaped the way it is today. Specifically, we intend to screen for genetic elements affecting Htt repeat length instability in dividing and postmitotic neuronal cells. The novelty of our approach relies on the construction of a human embryonic stem (hES) cell platform that couples highly efficient CRISPR/Cas9 technology with genome-wide screenings and third generation sequencing, to test the contribution of thousands of unequivocally barcoded cis and trans modifiers on Htt exon 1 repeats instability.

In Aim 1, we will test the contribution of cis-modifiers to repeat instability during multiple mitotic divisions, by generating a hES cell platform where we will subsequently introduce a barcoded donor library of different Htt exon 1 constructs, with different CAG and flanking sequences, at the Htt locus. In Aim 2 our hES cell platform will be implemented with inducible Cas9 elements and sgRNAs libraries to perform genome-wide loss and gain of function (LOF, GOF) screenings of trans-acting modifiers of repeat sequence and size. The sgRNAs will act as barcodes for the modifier genes, allowing to test their causative role on repeat size changes. In Aim 3, we will exploit the neurogenic potential of hES cells in our LOF and GOF platforms to identify Htt exon 1 repeat modifiers in differentiating striatal neurons. Candidate modifier genes will be individually validated and tested for their functional impact on gene networks by transcriptome analysis. In all approaches, third generation sequencing and ad hoc computational pipelines will allow the simultaneous identification of the repeat changes and their association to the corresponding modifiers. Overall, this research proposal is expected to provide key molecular and genetic insights into the process of Htt repeat expansion in human

Are you the coordinator (or a participant) of this project? Plaese send me more information about the "HD-DITTOGRAPH" project.

For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.

Send me an  email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.

Thanks. And then put a link of this page into your project's website.

The information about "HD-DITTOGRAPH" are provided by the European Opendata Portal: CORDIS opendata.

More projects from the same programme (H2020-EU.1.1.)

evolSingleCellGRN (2019)

Constraint, Adaptation, and Heterogeneity: Genomic and single-cell approaches to understanding the evolution of developmental gene regulatory networks

Read More  

HEIST (2020)

High-temperature Electrochemical Impedance Spectroscopy Transmission electron microscopy on energy materials

Read More  

IMMUNOTHROMBOSIS (2019)

Cross-talk between platelets and immunity - implications for host homeostasis and defense

Read More