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Objectives of Research

These studies (which involve collaborations with colleagues in Israel, Switzerland, Canada, and the U.S.A.) are directed toward elucidating the mechanisms and energetics of energy transduction and oscillation in biochemistry and physiology. The techniques used are mathematical modelling and computer simulation based on experimentally determined parameters, taking into account the kinetics and thermodynamics of the system. Recent work includes the bacterial flagellar motor, focusing on both the switching and torque-generating processes, and the genesis of the ultradian rhythm of growth hormone secretion.

Recent Findings

Switching flagellar rotation from one direction to another is an essential part of bacterial chemotaxis. We have demonstrated that fumarate facilitates the switching of the flagellar motor from counter-clockwise rotation to clockwise rotation by reducing the standard free energy difference of the switching transition. In attempting to understand the rotary mechanism, we have developed an electrostatic model for the flagellar motor which, in contrast to similar approaches developed earlier, reproduces closely a large number of experimental findings including the nonlinear behavior of the torque-frequency relation in E. coli, the stoichiometry of the system, and the stepping character of the motor. It demonstrates that the proton flux through the motor and the rotation are tightly coupled.

Growth hormone (GH) induces growth in animals and humans and also has important metabolic functions. The typical GH profile in the male rat shows secretory episodes every 3.3 h. Focusing on the mechanisms generating this rhythm we simulated the time course of GH secretion under a variety of conditions. The model we propose is based on feedback of GH on its own release mediated both by GH receptors on somatostatin (SRIF) neurons in the brain and by a delayed SRIF release into both the brain and portal blood. This affects both the somatotroph cells in the pituitary and the GH-releasing hormone (GHRH) neurons in the hypothalamus. The secretion of GHRH is postulated to occur in an approximately 1-h rhythm modulated by the level of SRIF. The model predicts a possible mechanism for the feminization of the male GH rhythm by sex steroids and vice versa, and suggests experiments that might reveal the proposed intrinsic 1-h GHRH rhythm. A feasible source of this rhythm is suggested and simulated.