Explore the words cloud of the Drug-Seq project. It provides you a very rough idea of what is the project "Drug-Seq" about.
The following table provides information about the project.
|Coordinator Country||France [FR]|
|Total cost||1˙999˙900 €|
|EC max contribution||1˙999˙900 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2015-09-01 to 2021-08-31|
Take a look of project's partnership.
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.
|year||authors and title||journal||last update|
Emmanouil Zacharioudakis, Poonam Agarwal, Alexandra Bartoli, Nathan Abell, Lavaniya Kunalingam, ValÃ©rie Bergoglio, Blerta Xhemalce, Kyle M. Miller, RaphaÃ«l 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|
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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The information about "DRUG-SEQ" are provided by the European Opendata Portal: CORDIS opendata.
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