Nonlinear dynamics of cellular signal transduction

Syracuse University, Syracuse NY

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Abstract

DESCRIPTION (Provided by Applicant): Sensory signal processing will be studied in the unicellular alga, Chlamydomonas reinhardtii. Its sensory network controls two cilia that propel and steer the cell through its aqueous environment, and allow it to track a light source (phototaxis). The specific aims are a) to identify components of the system that are important and predictive of the phototaxis behavior and b) to determine the nature and importance of the interactions among these components. These goals are of general importance in biology, for every cell faces the complex task of evaluating multiple, and sometimes contradictory, sensory inputs. Responses must be well regulated for optimal performance. Cells employ sophisticated strategies such as nonlinear processing, adaptive feedback, and potentially chaotic control. To investigate these processes, an established model of ciliary motility has been chosen with an extensive database of known components. Three preparations will be studied on the time scale of important interactions: the intact cell, the detergent-permeabilized cell, and the deciliated living cell. The last two preparations allow selective study of two nonoverlapping portions, cilia and cell body respectively, of the transduction network. The dynamic responses are to be measured by a) stereo-CCD ciliary images sampled at 900 Hz and b) net electrical current of the deciliated cells. Modulation of selected wavelengths of light and varied temperature, viscosity, external pH, extracellular ion concentrations, and pharmacological agents will affect the ciliary responses. Internal uncontrolled variables associated with phototaxis; namely intraciliary calcium, pH, and membrane potential will be measured. The dynamic response information will be analyzed by suitable quantitative methods, and predictive models will be developed and tested. Analysis of mutations of the ciliary structures in Chlamydomonas has identified structural and biochemical components that relate to features of the dynamic response. With this new information, our current model of three nonlinear parallel pathways controlling the ciliary stroke frequency, phase, and stroke velocity during phototaxis will be refined. Analysis of the nonlinear dynamical behavior of the system should lead to an understanding of the integrated components that generate this cellular behavior. Since many diseases involve intracellular signaling, understanding the complex and inherently nonlinear strategies employed by cells is of broad clinical significance.