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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.

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

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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