Project Details
Projekt
Optogenetics-assisted identification of the rapid stress receptor in zebrafish
Applicant
Professorin Soojin Ryu, Ph.D.
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2016 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 315233583
Stress-related disorders, which include not only psychiatric disturbances such as post-traumatic stress disorder (PTSD), schizophrenia, anxiety and depression, but also heart, metabolic and vascular problems, represent tremendous societal cost, which is rapidly rising. One of the key conserved stress hormones are Glucocorticoids (GCs), which serve as a master regulator of diverse stress-induced changes in physiology and behavior. GCs have many targets and functions in both rapid and long-term time domain. There is large amount of information available on how GCs mediate long-term cellular changes. In stark contrast, despite decades of efforts, the mechanism by which GCs rapidly regulate animal behavior and physiology is largely unknown. The major bottleneck in this research area has been inability to identify the receptor responsible for fast effects of GCs, which is thought to be a novel GPCR distinct from the GC receptors that mediate long-term effects. Current approaches in the stress field have not yielded a solution to this problem primarily because methods to rapidly and specifically trigger GC responses have not been available. The goal of this project is to devise a new strategy using optogenetics in zebrafish to overcome this technical limitation and address this important biological and medical challenge. Specifically, we propose in this study to use optogenetics to develop a high throughput in vivo assay for rapid GC effects and to find the rapid GC receptor using a candidate reverse genetic approach. To validate the identity of the receptor, we will develop and implement for the first time light-activatable GPCRs in zebrafish. Finally, we will use the unique opportunity offered by this collaborative project to generate a larger library of light-activatable GPCRs with a focus on receptors identified in brain function and disseminate them to the community. This library will address the current lack of optogenetic tools to study this important receptor class in zebrafish. Thus, using optogenetics, this work will identify novel stress receptor(s), which will open new avenues to better understand stress disorders and create an important optogenetic resource for investigating receptors involved in diverse aspects of brain function.
DFG Programme
Priority Programmes
