Header

UZH-Logo

Maintenance Infos

A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells


Muller, K; Engesser, R; Metzger, S; Schulz, S; Kampf, M M; Busacker, M; Steinberg, T; Tomakidi, P; Ehrbar, M; Nagy, F; Timmer, J; Zubriggen, M D; Weber, W (2013). A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells. Nucleic Acids Research, 41(7):e77.

Abstract

Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system’s performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms.

Abstract

Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system’s performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms.

Statistics

Citations

48 citations in Web of Science®
53 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

40 downloads since deposited on 06 Aug 2013
12 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:06 Aug 2013 07:26
Last Modified:30 Aug 2017 16:34
Publisher:Oxford University Press
ISSN:0305-1048
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/nar/gkt002
PubMed ID:23355611

Download

Preview Icon on Download
Preview
Content: Published Version
Filetype: PDF
Size: 793kB
View at publisher