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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.

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

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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