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StoNets - Controlling and exploiting stochasticity in gene regulatory networks
Third-party funded project
Project title StoNets - Controlling and exploiting stochasticity in gene regulatory networks
Principal Investigator(s) Zavolan, Mihaela
Co-Investigator(s) Becskei, Attila
van Nimwegen, Erik
Project Members Mittal, Nitish
Gruber, Andreas
Martin, Georges
Vina Vilaseca, Arnau
Kaiser, Matthias
Blank, Diana
Lazzari, Gianrocco
Bellement-Théroué, Gwendoline
Grandy, William Aaron
Rzepiela, Andrzej
Breda, Jeremie
Baudrimont, Antoine
Rodak, Christoph
Crippa, Alessandro
Wolf, Luise
Silander, Olin
Galbusera, Luca
Vögeli, Sylvia
Hsu, Chieh
Hansen, Marie Mi Bonde
Jaquet, Vincent
Syed, Afzal Pasha
Jedlinski, Dominik
Julou, Thomas
Gencoglu, Mümün
Calero Viloria, Eduardo
Katsantoni, Maria
Organisation / Research unit Departement Biozentrum / Bioinformatics (van Nimwegen),
Departement Biozentrum / Bioinformatics (Zavolan),
Departement Biozentrum / Synthetic Microbiology (Becskei)
Project Website http://www.systemsx.ch/projects/research-technology-and-development-projects/stonets/
Project start 01.03.2013
Probable end 28.02.2017
Status Completed
Abstract

The precision with which cells undergo differentiation programs or respond to external stimuli is remarkable, especially when considering the inherently "noisy" molecular interactions underlying these processes. StoNets aims to understand how stochasticity is controlled - and even exploited - to allow the development of robust behaviors of genetic networks, cells and cellular systems.

Although all cells within an organism carry the same genetic information, regulatory mechanisms that operate at essentially all steps of gene expression lead to a large variety of cell types and behaviors. Progress in measurement technologies has enabled the precise and high-throughput probing of molecules and cells. This in turn has revealed that stochasticity is pervasive in all gene expression regulatory systems. The central question we will address in this StoNets project is how robust and reproducible cellular behaviors can emerge in spite of these noisy molecular interactions.

A "slice" across the levels of gene expression organization

We will undertake a systematic investigation into the mechanisms that have emerged to control noise at different organizational scales of gene expression regulation, from transcription of individual genes to cell fate switching. Each of the example systems that we selected is interesting in its own right and exhibits important stochastic aspects.

Questions motivated by modeling

With the continuous progress in understanding the basic mechanisms of gene regulation, many key molecular players have been identified and numerous direct regulatory interactions have been mapped. Theoreticians have started to model the way in which specific behaviors emerge from the underlying interactions. These efforts have led to a large number of new, inherently quantitative questions regarding the biological systems. Through a very tight integration of experimental and computational approaches StoNets aims to answer such questions ultimately contributing to an improved, quantitative understanding and thereby controllability of cellular behaviors.

Financed by Swiss Government (Research Cooperations)

Published results ()

  ID Autor(en) Titel ISSN / ISBN Erschienen in Art der Publikation
3208056  Breda, Jeremie; Rzepiela, Andrzej J; Gumienny, Rafal; van Nimwegen, Erik; Zavolan, Mihaela  Quantifying the strength of miRNA-target interactions  1046-2023  Methods  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
2637564  Baresic, Mario; Salatino, Silvia; Kupr, Barbara; van Nimwegen, Erik; Handschin, Christoph  Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program  1098-5549  Molecular and cellular biology  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
4234977  Kaiser, Matthias; Jug, Florian; Julou, Thomas; Deshpande, Siddharth; Pfohl, Thomas; Silander, Olin K.; Myers, Gene; van Nimwegen, Erik  Monitoring single-cell gene regulation under dynamically controllable conditions with integrated microfluidics and software  2041-1723  Nature Communications  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
4487357  Rzepiela, Andrzej J.; Ghosh, Souvik; Breda, Jeremie; Vina-Vilaseca, Arnau; Syed, Afzal P.; Gruber, Andreas J.; Eschbach, Katja; Beisel, Christian; van Nimwegen, Erik; Zavolan, Mihaela  Single-cell mRNA profiling reveals the hierarchical response of miRNA targets to miRNA induction  1744-4292  Molecular systems biology  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
4639778  Urchueguía, Arantxa; Galbusera, Luca; Chauvin, Dany; Bellement, Gwendoline; Julou, Thomas; van Nimwegen, Erik  Genome-wide gene expression noise in Escherichia coli is condition-dependent and determined by propagation of noise through the regulatory network  1544-9173 ; 1545-7885  PLoS Biology  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 

Cooperations ()

  ID Kreditinhaber Kooperationspartner Institution Laufzeit - von Laufzeit - bis
2310066  Zavolan, Mihaela; van Nimwegen, Erik  Naef, Felix  EPFL  01.03.2013  31.12.2017 
2310071  Zavolan, Mihaela; van Nimwegen, Erik  Lutolf, Matthias  EPFL  01.03.2013  31.12.2017 
2310073  Zavolan, Mihaela; van Nimwegen, Erik  Gatfield, David  Université de Lausanne  01.03.2013  31.12.2017 
2331193  van Nimwegen, Erik  Zavolan, Mihaela  Biozentrum, University of Basel  01.01.2000  31.12.2099 
2337900  van Nimwegen, Erik  Pfohl, Thomas  Dep. Chemistry, University of Basel  01.03.2013  31.12.2020 
2337906  van Nimwegen, Erik  Myers, Eugene  Max Planck Institute of Molecular Cell Biology and Genetics  01.03.2013  31.12.2025 
   

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