Development and Validation of Computational Models for Mammalian Circadian Oscillators

Daniel B. Forger, Dennis A. Dean, Katherine Gurdziel, Jean Christophe Leloup, Choogon Lee, Charlotte Von Gall, Jean Pierre Etchegaray, Richard E. Kronauer, Albert Goldbeter, Charles S. Peskin, Megan E. Jewett, David R. Weaver

Research output: Contribution to journalArticlepeer-review

Abstract

Circadian rhythms are endogenous rhythms with a cycle length of approximately 24 h. Rhythmic production of specific proteins within pacemaker structures is the basis for these physiological and behavioral rhythms. Prior work on mathematical modeling of molecular circadian oscillators has focused on the fruit fly, Drosophila melanogaster. Recently, great advances have been made in our understanding of the molecular basis of circadian rhythms in mammals. Mathematical models of the mammalian circadian oscillator are needed to piece together diverse data, predict experimental results, and help us understand the clock as a whole. Our objectives are to develop mathematical models of the mammalian circadian oscillator, generate and test predictions from these models, gather information on the parameters needed for model development, integrate the molecular model with an existing model of the influence of light and rhythmicity on human performance, and make models available in BioSpice so that they can be easily used by the general community. Two new mammalian models have been developed, and experimental data are summarized. These studies have the potential to lead to new strategies for resetting the circadian clock. Manipulations of the circadian clock can be used to optimize performance by promoting alertness and physiological synchronization.

Original languageEnglish (US)
Pages (from-to)387-400
Number of pages14
JournalOMICS A Journal of Integrative Biology
Volume7
Issue number4
DOIs
StatePublished - 2003

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

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