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Circadian Rhythm: A Natural, Robust, Multi-scale Control System

Understanding regulation is a critical hurdle in unraveling complex biological systems. As gene-level architectures become known, the open challenge is to assign predictable behavior to a known structure, the so-called "genotype-to-phenotype" problem. In response to this challenge, the discipline of systems biology has emerged with an integrative perspective towards determining complex systems behavior. A property of particular interest is the /robustness /of the biophysical network: the ability to maintain some target level of behavior or performance in the presence of uncertainty and/or perturbations. In biological systems, these disturbances can be environmental (heat, pH, etc.) or intrinsic to the organism (e.g., stochastic variations in protein levels). While preliminary results are available for simple (low-dimensional, deterministic) biological systems, general tools for analyzing these tradeoffs are the subject of active research. The gene network which underlies circadian rhythms is an ideal system for robustness studies, owing to its remarkable performance in a highly uncertain environment. The regulatory architecture responsible for robust maintenance of 24 hour cycles is analyzed as a control system. At the gene regulatory level, it is shown that performance attributes, notably phase timing, are controlled in a robust manner. At the next level in the hierarchy, it is shown that synchrony is achieved via signaling in populations of networked neurons to enable clock precision. Analyses will be presented for fly, mammalian, and plant systems.

Type of Seminar:
Public Seminar
Francis J. Doyle III
Department of Chemical Engineering, University of California, Santa Barbara
Feb 28, 2006   17.15

CAB G 51, Universitätsstr. 6
Contact Person:

Jörg Stelling
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Biographical Sketch:
Dr. Francis J. Doyle III holds the Duncan and Suzanne Mellichamp Chair in Process Control in the Department of Chemical Engineering at the University of California at Santa Barbara, as well as appointments in the Electrical Engineering Department, and the Biomolecular Science and Engineering Program. He is also the Associate Director of the Army Institute for Collaborative Biotechnologies. He received his B.S.E. from Princeton (1985), C.P.G.S. from Cambridge (1986), and Ph.D. from Caltech (1991), all in Chemical Engineering. Prior to his appointment at UCSB, he has held faculty appointments at Purdue University and the University of Delaware, and held visiting positions at DuPont, Weyerhaeuser, and Stuttgart University. He is the recipient of several research awards (including the NSF National Young Investigator, ONR Young Investigator, and Humboldt Research Fellowship) as well as teaching awards (including the Purdue Potter Award, and the ASEE Ray Fahien Award). He is currently the editor-in-chief of the IEEE Transactions on Control Systems Technology, and holds Associate Editor positions with the Journal of Process Control, the SIAM Journal on Applied Dynamical Systems, and Interface. His research interests are in systems biology, drug delivery for diabetes, and control of particulate processes.