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cis-CONTROL SIGNED

Decoding and controlling cell-state switching: A bottom-up approach based on enhancer logic

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Project "cis-CONTROL" data sheet

The following table provides information about the project.

Coordinator
VIB VZW 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

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 Belgium [BE]
 Total cost 1˙999˙660 €
 EC max contribution 1˙999˙660 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB VZW BE (ZWIJNAARDE - GENT) coordinator 1˙999˙660.00

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 Project objective

Cell-state switching in cancer allows cells to transition from a proliferative to an invasive and drug-resistant phenotype. This plasticity plays an important role in cancer progression and tumour heterogeneity. We have made a striking observation that cancer cells of different origin can switch to a common survival state. During this epigenomic reprogramming, cancer cells re-activate genomic enhancers from specific regulatory programs, such as wound repair and epithelial-to-mesenchymal transition.

The goal of my project is to decipher the enhancer logic underlying this canalization effect towards a common survival state. We will then employ this new understanding of enhancer logic to engineer synthetic enhancers that are able to monitor and manipulate cell-state switching in real time. Furthermore, we will use enhancer models to identify cis-regulatory mutations that have an impact on cell-state switching and drug resistance. Such applications are currently hampered because there is a significant gap in our understanding of how enhancers work.

To tackle this problem we will use a combination of in vivo massively parallel enhancer-reporter assays, single-cell genomics on microfluidic devices, computational modelling, and synthetic enhancer design. Using these approaches we will pursue the following aims: (1) to identify functional enhancers regulating cell-state switching by performing in vivo genetic screens in mice; (2) to elucidate the dynamic trajectories whereby cells of different cancer types switch to a common survival cell-state, at single-cell resolution; (3) to create synthetic enhancer circuits that specifically kill cancer cells undergoing cell-state switching.

Our findings will have an impact on genome research, characterizing how cellular decision making is implemented by the cis-regulatory code; and on cancer research, employing enhancer logic in the context of cancer therapy.

 Publications

year authors and title journal last update
List of publications.
2017 Zeynep Kalender Atak, Hana Imrichova, Dmitry Svetlichnyy, Gert Hulselmans, Valerie Christiaens, Joke Reumers, Hugo Ceulemans, Stein Aerts
Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
published pages: , ISSN: 1756-994X, DOI: 10.1186/s13073-017-0464-7
Genome Medicine 9/1 2019-04-18
2018 Kristofer Davie, Jasper Janssens, Duygu Koldere, Maxime De Waegeneer, Uli Pech, Łukasz Kreft, Sara Aibar, Samira Makhzami, Valerie Christiaens, Carmen Bravo González-Blas, Suresh Poovathingal, Gert Hulselmans, Katina I. Spanier, Thomas Moerman, Bram Vanspauwen, Sarah Geurs, Thierry Voet, Jeroen Lammertyn, Bernard Thienpont, Sha Liu, Nikos Konstantinides, Mark Fiers, Patrik Verstreken, Stein Aerts
A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain
published pages: 982-998.e20, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.05.057
Cell 174/4 2019-04-18
2017 Sara Aibar, Carmen Bravo González-Blas, Thomas Moerman, Vân Anh Huynh-Thu, Hana Imrichova, Gert Hulselmans, Florian Rambow, Jean-Christophe Marine, Pierre Geurts, Jan Aerts, Joost van den Oord, Zeynep Kalender Atak, Jasper Wouters, Stein Aerts
SCENIC: single-cell regulatory network inference and clustering
published pages: 1083-1086, ISSN: 1548-7091, DOI: 10.1038/nmeth.4463
Nature Methods 14/11 2019-04-18
2018 Jelle Jacobs, Mardelle Atkins, Kristofer Davie, Hana Imrichova, Lucia Romanelli, Valerie Christiaens, Gert Hulselmans, Delphine Potier, Jasper Wouters, Ibrahim I. Taskiran, Giulia Paciello, Carmen B. González-Blas, Duygu Koldere, Sara Aibar, Georg Halder, Stein Aerts
The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes
published pages: 1011-1020, ISSN: 1061-4036, DOI: 10.1038/s41588-018-0140-x
Nature Genetics 50/7 2019-04-18
2018 Mark W E J Fiers, Liesbeth Minnoye, Sara Aibar, Carmen Bravo González-Blas, Zeynep Kalender Atak, Stein Aerts
Mapping gene regulatory networks from single-cell omics data
published pages: 246-254, ISSN: 2041-2649, DOI: 10.1093/bfgp/elx046
Briefings in Functional Genomics 17/4 2019-04-18
2018 Florian Rambow, Aljosja Rogiers, Oskar Marin-Bejar, Sara Aibar, Julia Femel, Michael Dewaele, Panagiotis Karras, Daniel Brown, Young Hwan Chang, Maria Debiec-Rychter, Carmen Adriaens, Enrico Radaelli, Pascal Wolter, Oliver Bechter, Reinhard Dummer, Mitchell Levesque, Adriano Piris, Dennie T. Frederick, Genevieve Boland, Keith T. Flaherty, Joost van den Oord, Thierry Voet, Stein Aerts, Amanda W. Lund, Jean-Christophe Marine
Toward Minimal Residual Disease-Directed Therapy in Melanoma
published pages: 843-855.e19, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.06.025
Cell 174/4 2019-02-25

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