Journal Article

A Synthetic Optogenetic Transcription Device Enhances Blood-Glucose Homeostasis in Mice

Ye, Haifeng, Peng, Ren-Wang, Baba, Marie Daoud-El, Fussenegger, Martin

2011

Overview

Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines grown in culture or bioreactors or implanted into mice. In animals harboring intraperitoneal hollow-fiber or subcutaneous implants containing light-inducible transgenic cells, the serum levels of the human glycoprotein secreted alkaline phosphatase could be remote-controlled with fiber optics or transdermally regulated through direct illumination. Light-controlled expression of the glucagon-like peptide 1 was able to attenuate glycemic excursions in type II diabetic mice. Synthetic light-pulse—transcription converters may have applications in therapeutics and protein expression technology.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: alkaline phosphatase / Alkaline Phosphatase - genetics / Alkaline Phosphatase - metabolism / animal disease models / Animals / Biological and medical sciences / Bioreactors / Biotechnology / Blood / blood glucose / Blood Glucose - metabolism / blood serum / Calcium / Cascade control / Cell culture techniques / Cell Line / Cell Line, Tumor / Cell lines / Chemical synthesis / Circuit design / Devices / Diabetes / Diabetes complications / Diabetes Mellitus, Type 2 - genetics / Diabetes Mellitus, Type 2 - metabolism / Fiber optics / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression Regulation / Genes, Reporter / Genetic Engineering - methods / Genetic technics applied to diagnosis / genetically modified organisms / glucagon-like peptide 1 / Glucagon-Like Peptide 1 - genetics / Glucagon-Like Peptide 1 - metabolism / Glucose / glycoproteins / GPI-Linked Proteins - genetics / GPI-Linked Proteins - metabolism / Health. Pharmaceutical industry / HEK293 cells / Homeostasis / Humans / Illumination / Industrial applications and implications. Economical aspects / Insulin - blood / Isoenzymes - genetics / Isoenzymes - metabolism / Light / Light Signal Transduction / lighting / Medical treatment / Mice / NFATC Transcription Factors - genetics / NFATC Transcription Factors - metabolism / Optical Fibers / Optics / optogenetics / Peptides / protein synthesis / Rod Opsins - genetics / Rod Opsins - metabolism / Rodents / Signal Transduction / synthetic biology / Synthetic Biology - methods / T-lymphocytes / therapeutics / Transcription, Genetic / Transfection / Transgenes