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Toward to Logical and Integrative Understaing of Human

Department of Integrative and Systems Physiology

Research

Outline

Integrative and Systems Physiology

We have been studying physiology at molecular, cellular and system levels, utilizing techniques combining experimental and mathematical methods, to clarify mechanisms of life and to seek novel strategies controlling living body.


Major projects

1. Study on the mechanisms underlying cardiac physiology/pathophysiology, focusing on intracellular cellular ion dynamics

Intracellular ion concentrations dynamically change (cellular ion dynamics) and are pivotal factors controlling excitation-contraction coupling of ordinary cardiac muscle cells (ventricular and atrial cells). They also play important roles in making a rhythm of specialized cardiac muscle cells (sinoatrial node and atrioventricular node cells). We have been studying the mechanisms of the cellular ion dynamics and seeking new strategies for controlling cardiac cell functions.

a) Experiments on cell physiology

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We study how individual molecules, such as channels/transporters, control cardiac cell functions using freshly isolated ventricular, atrial and sinoatrial node cells as well as cardiac cell line HL-1. We perform electrophysiological experiments, cell motion analyses as well as imaging analyses using fluorescence dyes or proteins in the normal cells and the specific gene knockout/knockdown cells.









b) Systems physiological analysis using mathematical models

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To overcome the limitation of experimental approach and to integrate a large body of scientific findings, we develop comprehensive mathematical models of cells and tissues based on the experimental data, and perform simulation analysis so as to clarify the underlying mechanisms. The representative models are models of ventricular cell, atrial cell, sinoatrial nodal cell and HL-1 cell. By repeating a cycle of gdevelopment of simulation-based working hypothesish and gexperimental validationh, we have clarified quantitatively contribution of each component of the cell on the cardiac cellular functions. In addition, we analyze how an abnormal activity of a component causes the failure of cellular function.




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2. Study on the mechanisms of ion dynamics of lymphocytes and their role in pathophysiology

Cytoplasmic Ca of lymphocytes increases upon various stimulations such as antigen binding to antigen receptors. We study the mechanisms of ion dynamics of lymphocytes and the relationship between ion dynamics and immune abnormality. We succeeded in developing a comprehensive model of Ca dynamics of lymphocyte and elucidated that a novel mitochondrial Ca transporter plays a major role in immunological responses of B lymphocytes.








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