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EPICODE SIGNED

Programmable Readers, Writers, and Erasers of the Epigenetic Cytosine Code

Total Cost €

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EC-Contrib. €

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Partnership

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 EPICODE project word cloud

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

watson    dynamic    analogs    tales    contrast    universality    human    decoded    selectivity    simplicity    synthesized    diagnosis    toolbox    consist    whereas    engineer    molecules    editing    writing    concatenated    biological    reading    enabled    spatiotemporal    biomarker    vitro    nucleobase    chromatin    cells    manner    tale    biologically    cancer    contains    regulatory    expanded    first    crick    resolution    broadly    detection    epigenetics    mc    acids    photoactivatable    encode    shapes    modules    hmc    loci    exist    fusions    class    programmable    nucleic    novo    scaffold    dna    trigger    single    sciences    de    canonical    nucleobases    epigenetic    types    insights    base    identity    central    typing    genomic    activator    applicable    synthesis    therapy    revolutionary    proteins    regulation    rnas    erasing    methodology    perturbation    recognition    transcription    employ    recognizes    imprinting    cac    molecular    cell    regulate    pairing    profiling    reported    fc    effectors    vivo    phenotype    instructive   

Project "EPICODE" data sheet

The following table provides information about the project.

Coordinator
TECHNISCHE UNIVERSITAT DORTMUND 

Organization address
address: AUGUST SCHMIDT STRASSE 4
city: DORTMUND
postcode: 44227
website: www.tu-dortmund.de

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 Germany [DE]
 Total cost 1˙979˙679 €
 EC max contribution 1˙979˙679 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-11-01   to  2022-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    TECHNISCHE UNIVERSITAT DORTMUND DE (DORTMUND) coordinator 1˙979˙679.00

Map

 Project objective

Human DNA contains two types of biologically instructive information: the canonical nucleobases A, G, T, C, and the epigenetic nucleobases mC, hmC, fC, and caC. Canonical nucleobases encode the identity of all RNAs and proteins that are synthesized by a cell, whereas epigenetic nucleobases regulate this synthesis. This regulation shapes the phenotype of cells, and its perturbation is a key trigger of cancer. Canonical nucleobases can be decoded in a programmable manner by nucleic acids and their analogs via Watson-Crick-base pairing, and the simplicity of this recognition has enabled revolutionary developments in the biological sciences. In contrast, comparable developments in epigenetics have not yet been possible, since a molecular scaffold with programmable recognition of epigenetic nucleobases does not exist. We will establish the first class of molecules capable of the expanded programmable recognition of both canonical and epigenetic DNA nucleobases in vitro and in vivo. This is based on transcription-activator-like effectors (TALEs) that consist of four types of concatenated modules, each of which recognizes a canonical nucleobase. We have recently reported the detection of single epigenetic nucleobases by TALEs. In this project, we will 1. engineer a toolbox of TALE modules with selectivity for C, mC, hmC, fC, and caC, 2. employ them for TALE-based in vitro typing and profiling (reading) of cancer biomarker mC/hmC, and 3. design photoactivatable TALE-fusions that enable the writing and erasing of mC at user-defined genomic loci in vivo with spatiotemporal resolution. This will provide the first insights into the dynamic effects of de novo editing on chromatin regulation, and enables the imprinting of regulatory states. Given the central role of epigenetic nucleobases in cancer and the universality of our approach, this project will provide enabling and broadly applicable methodology for cancer epigenetics research, diagnosis and therapy.

 Publications

year authors and title journal last update
List of publications.
2018 S. Maurer, B. Buchmuller, C. Ehrt, J. Jasper, O. Koch and D. Summerer*
Overcoming conservation in TALE-DNA interactions: A minimal repeat scaffold enables selective rerognition of an oxidized 5-methylcytosine
published pages: , ISSN: 2041-6520, DOI:
Chem. Sci. 2019-06-27
2019 T. Braun, M. Drescher* and D. Summerer*
Expanding the genetic code for site-directed spin-labeling
published pages: , ISSN: 1422-0067, DOI:
Int. J. Mol. Sci. 2019-06-27
2018 H. Neumann*, P. Neumann-Staubitz, A. Witte and D. Summerer*
Epigenetic chromatin modification by amber suppression technology
published pages: , ISSN: 1367-5931, DOI:
Curr. Opin. Chem. Biol. 2019-06-27
2019 M. Giess, A. Munoz-Lopez, B. Buchmuller, G. Kubik and D. Summerer*
Programmable Protein-DNA Crosslinking for the Direct Capture and Quantification of 5-Formylcytosine
published pages: , ISSN: 0002-7863, DOI:
J. Am. Chem. Soc. 2019-06-27

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