EPICODE SIGNED
Programmable Readers, Writers, and Erasers of the Epigenetic Cytosine Code
Total Cost €
0EC-Contrib. €
0Partnership
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0EPICODE 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.
Project "EPICODE" data sheet
The following table provides information about the project.
| Coordinator |
TECHNISCHE UNIVERSITAT DORTMUND
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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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