title: A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice.
abstract: 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.
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zurich, Basel, Switzerland.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Ye
authors.forename: Marie
authors.initials: M
authors.lastname: Daoud-El Baba
authors.forename: Ren-Wang
authors.initials: RW
authors.lastname: Peng
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019149:Bioreactors; D001786:Blood Glucose / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005818:Genetic Engineering / Q000379:methods*; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008027:Light; D055537:Light Signal Transduction; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D055100:Optical Fibers; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058615:Synthetic Biology / Q000379:methods*; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes; D000099210:Melanopsin
chemical_list: D000469:Alkaline Phosphatase; D001786:Blood Glucose; D058851:GPI-Linked Proteins; D052216:Glucagon-Like Peptide 1; D007328:Insulin; D007527:Isoenzymes; D050778:NFATC Transcription Factors; D017299:Rod Opsins; D000099210:Melanopsin; C019839:alkaline phosphatase, placental