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Drug-Seq SIGNED

Unravelling the Genomic Targets of Drugs Using High-Throughput Sequencing

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 Drug-Seq project word cloud

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

anticipate    decipher    molecule    chip    interactions    specificity    cancers    interrogate    proteins    regulating    firstly    chemistry    lay    small    putative    interactome    collectively    foundation    disease    agents    camptothecin    rational    landmark    interfere    cell    situ    drug    death    independent    etoposide    genome    medicine    precipitation    cellular    mechanisms    vivo    affinity    exact    perform    critical    probes    seek    replication    dna    discovery    clinical    interacting    protocols    act    lines    sites    instability    modulate    landscape    location    throughput    click    pull    regular    techniques    damaging    epigenome    sequencing    immuno    linked    enquiry    thereby    validate    elucidate    unbiased    genomic    druggable    secondly    trigger    methodology    universal    genotoxic    operate    understand    seq    combine    molecular    innovative    cisplatin    compounds    rationalize    treat    decades    centred    transcription    empirical    map    chromatin    personalized    followed    models    drugs   

Project "Drug-Seq" data sheet

The following table provides information about the project.

Coordinator
INSTITUT CURIE 

Organization address
address: rue d'Ulm 26
city: PARIS
postcode: 75231
website: www.curie.fr

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 France [FR]
 Total cost 1˙999˙900 €
 EC max contribution 1˙999˙900 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT CURIE FR (PARIS) coordinator 1˙999˙900.00

Map

 Project objective

This proposal is centred on the development of small molecule probes derived from DNA damaging agents to identify their genomic targets using a novel unbiased approach. Although, several genotoxic drugs have been used for decades to treat cancers, the exact mechanisms by which they operate are not fully understood. It is established that these compounds interfere with the processes of transcription and replication, thereby promoting genomic instability and cell death. However, there is as yet no genome-wide map of the exact location of sites that are putative targets for these drugs in vivo. This information is critical to understand and rationalize cellular responses to genotoxic agents. Here, we propose to develop an innovative discovery- based methodology that will combine click chemistry in situ, affinity pull-down techniques and high throughput DNA sequencing (Drug-Seq), to identify the genomic interactome of DNA damaging drugs in order to elucidate their cellular activity at the molecular level. Two independent lines of enquiry will be followed. Firstly, we will establish the genomic interacting landscape of landmark drugs including etoposide, camptothecin and cisplatin using Drug-Seq. Secondly, we will perform regular chromatin immuno- precipitation sequencing (ChIP-Seq) of selected proteins linked to the cellular response of interest to validate Drug-Seq and further identify druggable genomic sites. An important aim of this proposal is to establish a universal methodology to decipher small molecule/genome interactions in vivo that trigger a particular response in disease-relevant models. We also seek to interrogate the role of chromatin in regulating drug/genome interactions and to define whether it is possible to act on the epigenome to modulate the activity and specificity of these drugs. Collectively, we anticipate our study will lay down the foundation for personalized medicine with the implementation of rational rather than empirical clinical protocols.

 Publications

year authors and title journal last update
List of publications.
2017 Emmanouil Zacharioudakis, Poonam Agarwal, Alexandra Bartoli, Nathan Abell, Lavaniya Kunalingam, Valérie Bergoglio, Blerta Xhemalce, Kyle M. Miller, Raphaël Rodriguez
Chromatin Regulates Genome Targeting with Cisplatin
published pages: 6483-6487, ISSN: 1433-7851, DOI: 10.1002/anie.201701144
Angewandte Chemie International Edition 56/23 2019-09-02
2018 Gabriel Balmus, Delphine Larrieu, Ana C. Barros, Casey Collins, Monica Abrudan, Mukerrem Demir, Nicola J. Geisler, Christopher J. Lelliott, Jacqueline K. White, Natasha A. Karp, James Atkinson, Andrea Kirton, Matt Jacobsen, Dean Clift, Raphael Rodriguez, David J. Adams, Stephen P. Jackson
Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03770-3
Nature Communications 9/1 2019-09-02

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