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- 연자 : 김정우 박사 (Department of Molecular and Cell Biology  University of California, Berkeley)
- 제목 : Spontaneous Activity and Gene Expression: A Window into Homeostatic Integrity
- 일시 : 2025년 4월 18일 목요일 오후1시 30분
- 장소 : 연구관 708호 회의실

Spontaneous neural activity—once dismissed as background noise—is now recognized as a cornerstone of brain function. Notably, this activity is tightly regulated by homeostatic mechanisms that keep the integrity of brain function. Dysregulation of spontaneous activity is a hallmark of diverse brain disorders, ranging from neurodevelopmental to neurodegenerative diseases, positioning it as both an indicator of homeostatic regulation and a critical lens for understanding disease mechanisms.

Despite its significance, gene expression programs governing spontaneous activity remain poorly understood. A major challenge has been the absence of methodologies enabling biochemical and molecular analyses tied to spontaneous activity levels. To address this, I developed calcium-dependent protein labeling technologies that leverage calcium influx to biotinylate proteins, providing a biochemical approach to access spontaneously active neurons.

First, I engineered Cal-ID, a calcium-activated promiscuous labeling enzyme, which enabled whole-brain-scale biochemical tagging of spontaneously active neurons. Next, I generated CalTRAP-seq (Calcium-dependent ribosome labeling, pulldown and sequencing), a technology designed to capture gene expression signatures specific to spontaneously active neurons. Using CalTRAP-seq, we discovered a novel activity-dependent gene expression program that is tightly coupled to intracellular calcium influx yet distinct from canonical stimulus-responsive gene expression, such as immediate early gene induction. Furthermore, we found that alternative splicing of synaptic genes is a major component of spontaneous activity-associated gene expression.

Through these novel high-throughput approaches, my future research aims to unravel the cellular and molecular mechanisms governing homeostatic regulation of neuronal activity and to explore its significance in neurodegeneration. These insights hold promise for pioneering therapeutic strategies for brain disorders associated with activity dysregulation.

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