Multi-chromatic control of mammalian gene expression and signaling

被引：113

作者：

Mueller, Konrad ^{[1
]}

Engesser, Raphael ^{[2
,3
]}

Schulz, Simon ^{[4
]}

Steinberg, Thorsten ^{[4
]}

Tomakidi, Pascal ^{[3
,4
]}

Weber, Cornelia C. ^{[5
]}

Ulm, Roman ^{[6
]}

Timmer, Jens ^{[2
,3
,7
,8
]}

Zurbriggen, Matias D. ^{[1
]}

Weber, Wilfried ^{[1
,3
,7
]}

机构：

[1] Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany

[2] Univ Freiburg, Dept Phys, D-79104 Freiburg, Germany

[3] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany

[4] Univ Hosp Freiburg, Dept Oral Biotechnol, D-79106 Freiburg, Germany

[5] Novartis Pharma AG, Biol Proc R&D, CH-4002 Basel, Switzerland

[6] Univ Geneva, Dept Bot & Plant Biol, CH-1211 Geneva 4, Switzerland

[7] Univ Freiburg, Freiburg Ctr Biosyst Anal ZBSA, D-79104 Freiburg, Germany

[8] Univ Freiburg, Freiburg Inst Adv Studies FRIAS, D-79104 Freiburg, Germany

来源：

NUCLEIC ACIDS RESEARCH | 2013年 / 41卷 / 12期

基金：

欧洲研究理事会;

关键词：

ENDOTHELIAL GROWTH-FACTOR; UV-B; SPATIOTEMPORAL CONTROL; PROTEIN INTERACTIONS; ESCHERICHIA-COLI; CELLS; LIGHT; ANGIOPOIETIN-1; MICE; ARABIDOPSIS;

D O I：

10.1093/nar/gkt340

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The emergence and future of mammalian synthetic biology depends on technologies for orchestrating and custom tailoring complementary gene expression and signaling processes in a predictable manner. Here, we demonstrate for the first time multi-chromatic expression control in mammalian cells by differentially inducing up to three genes in a single cell culture in response to light of different wavelengths. To this end, we developed an ultraviolet B (UVB)-inducible expression system by designing a UVB-responsive split transcription factor based on the Arabidopsis thaliana UVB receptor UVR8 and the WD40 domain of COP1. The system allowed high (up to 800-fold) UVB-induced gene expression in human, monkey, hamster and mouse cells. Based on a quantitative model, we determined critical system parameters. By combining this UVB-responsive system with blue and red light-inducible gene control technology, we demonstrate multi-chromatic multi-gene control by differentially expressing three genes in a single cell culture in mammalian cells, and we apply this system for the multi-chromatic control of angiogenic signaling processes. This portfolio of optogenetic tools enables the design and implementation of synthetic biological networks showing unmatched spatiotemporal precision for future research and biomedical applications.

引用

页数：11

共 61 条

[1] Induction of functional neovascularization by combined VEGF and angiopoietin-1 gene transfer using AAV vectors [J].