Curated Optogenetic Publication Database

Search precisely and efficiently by using the advantage of the hand-assigned publication tags that allow you to search for papers involving a specific trait, e.g. a particular optogenetic switch or a host organism.

Showing 1 - 4 of 4 results

Optical regulation of endogenous RhoA reveals switching of cellular responses by signal amplitude.

blue cyan CRY2/CIB1 Dronpa145K/N pdDronpa1 TULIP HEK293A rat hippocampal neurons U-87 MG Endogenous gene expression
bioRxiv, 7 Feb 2021 DOI: 10.1101/2021.02.05.430013 Link to full text
Abstract: Precise control of the timing and amplitude of protein activity in living cells can explain how cells compute responses to complex biochemical stimuli. The small GTPase RhoA can promote either focal adhesion (FA) growth or cell edge retraction, but how a cell chooses between these opposite outcomes is poorly understood. Here, we developed a photoswitchable RhoA guanine exchange factor (psRhoGEF) to obtain precise optical control of endogenous RhoA activity. We find that low levels of RhoA activation by psRhoGEF induces edge retraction and FA disassembly, while high levels of RhoA activation induces both FA growth and disassembly. We observed that mDia-induced Src activation at FAs occurs preferentially at lower levels of RhoA activation. Strikingly, inhibition of Src causes a switch from FA disassembly to growth. Thus, rheostatic control of RhoA activation reveals how cells use signal amplitude and biochemical context to select between alternative responses to a single biochemical signal.

A synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice.

blue CRY2/CIB1 LOVTRAP VVD A549 Cos-7 HEK293 HEK293T HeLa mouse in vivo NCI-H1299 PC-3 U-87 MG Transgene expression
Nat Commun, 27 Jan 2021 DOI: 10.1038/s41467-021-20913-1 Link to full text
Abstract: Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in stress response, signaling and development. Despite the fascinating discoveries made in the past few years, the mechanisms and functional capabilities of most pulsing systems remain unclear, and one of the critical challenges is the lack of a technology that allows pulsatile regulation of transgene expression both in vitro and in vivo. Here, we describe the development of a synthetic BRET-based transgene expression (LuminON) system based on a luminescent transcription factor, termed luminGAVPO, by fusing NanoLuc luciferase to the light-switchable transcription factor GAVPO. luminGAVPO allows pulsatile and quantitative activation of transgene expression via both chemogenetic and optogenetic approaches in mammalian cells and mice. Both the pulse amplitude and duration of transgene expression are highly tunable via adjustment of the amount of furimazine. We further demonstrated LuminON-mediated blood-glucose homeostasis in type 1 diabetic mice. We believe that the BRET-based LuminON system with the pulsatile dynamics of transgene expression provides a highly sensitive tool for precise manipulation in biological systems that has strong potential for application in diverse basic biological studies and gene- and cell-based precision therapies in the future.

Neurotrophin receptor tyrosine kinases regulated with near-infrared light.

blue red DrBphP TULIP CHO HeLa mouse in vivo NIH/3T3 PC6-3 SH-SY5Y U-87 MG Signaling cascade control Multichromatic
Nat Commun, 8 Mar 2019 DOI: 10.1038/s41467-019-08988-3 Link to full text
Abstract: Optical control over the activity of receptor tyrosine kinases (RTKs) provides an efficient way to reversibly and non-invasively map their functions. We combined catalytic domains of Trk (tropomyosin receptor kinase) family of RTKs, naturally activated by neurotrophins, with photosensory core module of DrBphP bacterial phytochrome to develop opto-kinases, termed Dr-TrkA and Dr-TrkB, reversibly switchable on and off with near-infrared and far-red light. We validated Dr-Trk ability to reversibly light-control several RTK pathways, calcium level, and demonstrated that their activation triggers canonical Trk signaling. Dr-TrkA induced apoptosis in neuroblastoma and glioblastoma, but not in other cell types. Absence of spectral crosstalk between Dr-Trks and blue-light-activatable LOV-domain-based translocation system enabled intracellular targeting of Dr-TrkA independently of its activation, additionally modulating Trk signaling. Dr-Trks have several superior characteristics that make them the opto-kinases of choice for regulation of RTK signaling: high activation range, fast and reversible photoswitching, and multiplexing with visible-light-controllable optogenetic tools.

A light-switchable bidirectional expression module allowing simultaneous regulation of multiple genes.

blue VVD Cos-7 HEK293 mouse in vivo NCI-H1299 U-87 MG Transgene expression
Biochem Biophys Res Commun, 21 Aug 2015 DOI: 10.1016/j.bbrc.2015.08.085 Link to full text
Abstract: Several light-regulated genetic circuits have been applied to spatiotemporally control transgene expression in mammalian cells. However, simultaneous regulation of multiple genes using one genetic device by light has not yet been reported. In this study, we engineered a bidirectional expression module based on LightOn system. Our data showed that both reporter genes could be regulated at defined and quantitative levels. Simultaneous regulation of four genes was further achieved in cultured cells and mice. Additionally, we successfully utilized the bidirectional expression module to monitor the expression of a suicide gene, showing potential for photodynamic gene therapy. Collectively, we provide a robust and useful tool to simultaneously control multiple genes expression by light, which will be widely used in biomedical research and biotechnology.
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