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Development Of Optical Imaging Tools For Synapse Typing Essay

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Development of Optical Imaging Tools for Synapse Typing
Restructure of synapse types and alternations of dynamics of neurotransmitters and neuromodulators have been implicated in a number of human neurological and psychiatric diseases, including autism, Alzheimer’s disease, Parkinson’s disease, schizophrenia, and addiction1,2. However, little is known about how molecular compositions define different types and functions of synapses and how different synapses organize in micro- and macroscale to give rise to complex brain functions and disorders, due to lack of appropriate tools to characterize synaptic biomolecules in situ in large scale. Here, I propose a novel research program to develop transformative tools for large-scale mapping of synaptic biomolecules, functional imaging of neurotransmission and neuronal signaling. Specifically, it will evolve along three main themes: 1. Expansion pathology for highly multiplexed, in situ and nanoscale biomolecular imaging. 2. Optogenetic neurotransmitter indicator; 3. in situ imaging tools for endogenous protein-protein interaction; This program will expand on the themes of my previous work on engineering optogenetic indicators for neuronal activities, such as calcium ions3,4 and voltage5,6 indicators, as well as my current work on devising a clinically optimized form of expansion microscopy7,8, which contribute new capabilities to the broader communities of neuroscience, cell biology, pathology and medicine.
Theme 1: Expansion

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