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RNAREG SIGNED

Single molecule observation and manipulation of gene expression dynamics to dissect mechanisms of cell cycle entry

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EC-Contrib. €

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Project "RNAREG" data sheet

The following table provides information about the project.

Coordinator
KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW 

Organization address
address: KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
city: AMSTERDAM
postcode: 1011 JV
website: www.knaw.nl

contact info
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 Coordinator Country Netherlands [NL]
 Project website http://www.tanenbaumlab.org
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW NL (AMSTERDAM) coordinator 1˙500˙000.00

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 Project objective

Gene expression is a highly dynamic and inherently variable process. Yet, it needs to be tightly regulated, especially during the cell cycle, when continuous large-scale changes occur to the proteome. Even small deviations in the expression levels of a single protein in individual cells can de-regulate cell cycle entry and promote tumorigenesis. Here, I will develop new technology to study gene expression dynamics in single cells to uncover how active regulation and stochastic variability shape the expression of key cell cycle genes and ensure reliable cell cycle-entry decisions. I recently developed a protein multimerization system, called SunTag, which allows very bright fluorescence imaging, as well as manipulation of transcription. To understand how accurate expression levels of a core set of cell cycle proteins are achieved, I will combine single-cell RNA sequencing with SunTag fluorescence imaging technology to visualize, with single molecule sensitivity, the rates of transcription, translation and mRNA degradation. These analyses will identify the contribution of each type of regulation to accurate gene expression, and will reveal how active regulation ensures correct cell cycle decisions in the presence of stochastic expression variability. Furthermore, I will develop new methodology to specifically perturb the different types of gene expression control during defined cell cycle stages. This will enable an unprecedented ability to interrogate the function of gene expression control for cell cycle entry, and will identify the genes for which tight control of expression is critical for correct cell cycle decisions. Together, this approach will:

1) Uncover how individual regulatory mechanisms (e.g. regulation of transcription, translation or mRNA degradation) contribute to accurate cell cycle entry through gene expression control of key cell cycle proteins

2) Examine how stochastic variability in gene expression influences the decision to enter the cell cycle

 Publications

year authors and title journal last update
List of publications.
2016 Xiaowei Yan, Tim A. Hoek, Ronald D. Vale, Marvin E. Tanenbaum
Dynamics of Translation of Single mRNA Molecules In Vivo
published pages: 976-989, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.04.034
Cell 165/4 2019-06-19
2017 Marco Jost, Yuwen Chen, Luke A. Gilbert, Max A. Horlbeck, Lenno Krenning, Grégory Menchon, Ankit Rai, Min Y. Cho, Jacob J. Stern, Andrea E. Prota, Martin Kampmann, Anna Akhmanova, Michel O. Steinmetz, Marvin E. Tanenbaum, Jonathan S. Weissman
Combined CRISPRi/a-Based Chemical Genetic Screens Reveal that Rigosertib Is a Microtubule-Destabilizing Agent
published pages: 210-223.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.09.012
Molecular Cell 68/1 2019-04-16

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The information about "RNAREG" are provided by the European Opendata Portal: CORDIS opendata.

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