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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.

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

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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