Research Topic

Next-Generation Genetically-Encoded Fluorescent Sensors

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Camillo Golgi and Santiago Ramón y Cajal shared the 1906 Nobel Prize in Physiology and Medicine for their innovative contributions to resolve the intricate structure of neurons with novel staining techniques and use of light microscopy. These have inspired and paved the way for new technologies to eavesdrop ...

Camillo Golgi and Santiago Ramón y Cajal shared the 1906 Nobel Prize in Physiology and Medicine for their innovative contributions to resolve the intricate structure of neurons with novel staining techniques and use of light microscopy. These have inspired and paved the way for new technologies to eavesdrop on neuronal structure and function in the living and behaving animal. Fast forward to the 20th century, the discovery and development of the green fluorescent protein (GFP) has unlocked unprecedented and powerful genetic means for highlighting defined neuronal populations. It has also prompted the development of genetically-encoded optical probes, making GFP one of the most important discoveries of our time.

Since, structural studies, progress in molecular biology, new microscopes and innovative thinking have enabled to expand the technicolor palette of fluorescent proteins along new and improved optical markers and probes, in particular Genetically-Encoded Indicators of Neuronal Activity (GINAs). First-generation GINAs emerged in the late 1990s, mainly using Förster Resonance Energy Transfer (FRET) between two FPs. The popularity of these probes progressively stimulated the evolution of additional probes of different colors, responding to different ligands, employing circularly permutated FP (cpFP) or other light-absorbing proteins altogether. Today, the use of GINAs is so widespread, most high-profile articles make use of at least one optical tool.

This Research Topic aims to introduce the reader to state-of-the-art principles and practices in biosensor development and highlight ways in which development of novel biosensors have illuminated outstanding questions of biological function. Specifically, we focus on sensors developed for monitoring neuronal activity, including:

- Variations of Ca2+-probes (monomerized CaM, inverse response)
- Hybrid/multi-functional sensors (e.g., probes fused to opsins, photoacoustic probes)
- Voltage sensors
- Neurotransmitter sensors (glutamate, Ach, GABA)
- Photoactivatable/convertible sensors
- Probes compatible with electron microscopy


Keywords: flourescence, probes, photoactivation, genetically-encoded, multi-functional


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