Research

Molecular-Level Understanding of ComplexBrain Functions

The brain is a remarkably complex tissue composed of neurons and glial cells, whose vast network of connection gives rise to its intricate functions such as thinking, emotion, and consciousness. A key to understanding the cellular connections underlying brain functions lies in unveiling the molecular systems orchestrated by diverse protein interactions. Our guiding principle, “bun-nou ittai” (which means ‘Brain function fundamentally resides within molecular systems’ in Japanese), reflects our commitment to describing brain function as a machinery driven by protein interactions. We aim to make a positive impact on society by investigating the underlying causes of neurological and psychiatric disorders, and discovering innovative diagnostic and therapeutic methods through molecular targeting.

① Development of Spatial Proteome Techniques Using BioID

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The human body comprises a vast diversity of proteins—over 100,000 species—resulting from alternative splicing and post-translational modifications. The precise regulation of these protein’s interactions contributes to the distinct roles of neural circuits, enabling higher brain functions. We are currently developing spatial proteome techniques utilizing biotin ligase-based proximity labeling (BioID) to investigate protein components within specific intracellular localizations and their interactions. This technique enables the effective identification of proteins localized to distinct intracellular regions, such as excitatory or inhibitory synapses, and pre- or post-synaptic sites, in specific cell types, such as neurons and glial cells, in vivo. These advances enhance our understanding of the molecular systems underlying brain function.

② Unveiling the Mechanisms Underlying Synaptic Diversity

The human brain comprises approximately 150 trillion synapses, each playing distinct roles based on neuron type and protein components. This synaptic diversity enables a wide range of brain functions, including memory, emotion, decision-making, and social interactions. Additionally, astrocytes—a type of glial cell—form tripartite synapses with neurons, finely tuning the information processing between neurons. Our research seeks to unravel the comprehensive molecular mechanisms that drive unique synaptic functions and uncover the molecular systems that underpin the brain’s remarkable plasticity and precision. We employ spatial proteomics, molecular biology techniques, biochemistry, tissue imaging, and behavioral experiments to explore these molecular systems.

③ Investigating the Pathology of Psychiatric and Neurodegenerative Disorders

Many psychiatric and neurological disease stem from dysfunctions in synapses and neural circuits. Our research seeks to uncover the fundamental causes of these disorders by identifying abnormalities in molecular systems within specific synapses and neural circuits. We focus on the connection between neural circuit dysfunction and mental disorders such as depression, anxiety disorders, and schizophrenia, as well as neurodegenerative diseases like Alzheimer’s disease. Using high-precision spatial proteomics, we are working to clarify the molecular disruptions that underlie brain dysfunction in these pathologies. Ultimately, we aim to establish a molecular framework for early diagnosis and innovative molecular-targeted therapies.