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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.

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

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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