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RetroNets SIGNED

Reverse Engineering Gene Regulatory Networks

Total Cost €

EC-Contrib. €

Partnership

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RetroNets project word cloud

Explore the words cloud of the RetroNets project. It provides you a very rough idea of what is the project "RetroNets" about.

cerevisiae grn engineering copy output native model function predicting sequence zn orthogonal master transcriptional deciphering achievement translating technologies entire predictive central input regulatory trivial mapping mechanism finger integrate yeast promoter evolve manner microfluidic vitro regulation networks expression tf optimized cellular gene exact vivo engineered group predict engineer computationally appropriate nonetheless topology considerable phosphate nor inorganic grns network genome transcription functional prerequisite quantitative promoters ultimately details quantitatively cas concentrations fitness relationship signal computational throughput progress incorporating poorly powerful disciplinary biological phenotypes made reverse signals components link cells biology modulating crispr

Project "RetroNets" data sheet

The following table provides information about the project.

Coordinator	ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Organization address address: BATIMENT CE 3316 STATION 1 city: LAUSANNE postcode: 1015 website: www.epfl.ch 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	Switzerland [CH]
Total cost	1˙993˙858 €
EC max contribution	1˙993˙858 € (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 2017-04-01 to 2022-03-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Organization address address: BATIMENT CE 3316 STATION 1 city: LAUSANNE postcode: 1015 website: www.epfl.ch contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	CH (LAUSANNE)	coordinator	1˙993˙858.00

Map

Project objective

Gene regulatory networks (GRNs) are an important cellular signal processing mechanism for translating input signals into appropriate phenotypes by modulating expression of the genome. The quantitative details of how cells process information through GRNs are still poorly understood, but of central importance in a large number of biological processes. Considerable progress has been made in mapping the topology of GRNs and more recently in deciphering the relationship between promoter sequence and function. Nonetheless, it is not yet possible to computationally predict the output of most native promoters, nor is it trivial to build promoters that integrate signals in a novel and predictive manner. Developing a quantitative understanding of transcriptional regulation, ultimately leading to the ability to predict entire GRNs will be a significant achievement and a prerequisite for our ability to engineer biological systems. I propose a multi-disciplinary approach incorporating biology, engineering, and computational modelling to improve our quantitative understanding by reverse engineering GRNs in S. cerevisiae. My research group has developed a powerful set of unique, high-throughput microfluidic technologies that enable the quantitative analysis of GRNs in vitro and in vivo. Specifically I propose to quantitatively investigate the yeast phosphate regulatory network and to develop a master model capable of predicting output of the network under various inorganic phosphate concentrations, to develop novel approaches for modulating GRNs using engineered Zn-finger transcription factors (TF) and CRISPR/Cas, to link GRN output to fitness in order to develop an understanding of how networks are optimized and evolve, and to reverse engineer an exact functional copy of the native phosphate regulatory network with orthogonal components.

Publications

List of publications.
year	authors and title	journal	last update
2019	Zoe Swank, Nadanai Laohakunakorn, Sebastian J. Maerkl Cell-free gene-regulatory network engineering with synthetic transcription factors published pages: 5892-5901, ISSN: 0027-8424, DOI: 10.1073/pnas.1816591116	Proceedings of the National Academy of Sciences 116/13	2020-04-24
2017	Kristina Woodruff, Sebastian J. Maerkl Microfluidic Module for Real-Time Generation of Complex Multimolecule Temporal Concentration Profiles published pages: 696-701, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.7b04099	Analytical Chemistry 90/1	2020-04-24
2018	Jui-Chia Chang, Zoe Swank, Oliver Keiser, Sebastian J. Maerkl, Esther Amstad Microfluidic device for real-time formulation of reagents and their subsequent encapsulation into double emulsions published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-26542-x	Scientific Reports 8/1	2020-04-24

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