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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.

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

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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