- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2010-07-07 16:05:59+12:00
- Desc:
- Added images in ai and svg format
- Permanent Source URI:
- http://models.cellml.org/workspace/tyson_hong_thron_novak_1999/rawfile/fdfa4721aef1de524ba14af86e0cef555e558486/tyson_hong_thron_novak_1999.cellml
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<!-- FILE : tyson_model_1999.xml
CREATED : 1st October 2007
LAST MODIFIED : 1st October 2007
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Tyson et al.'s 1999 simple mathematical model of circadian rhythms based on dimerisation and proteolysis of PER and TIM.
CHANGES:
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<title>A Simple Model of Circadian Rhythms Based on Dimerization and Proteolysis of PER and TIM</title>
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<firstname>Catherine</firstname>
<surname>Lloyd</surname>
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This CellML version of the model has been checked in COR and PCEnv and the model runs to replicate the results in the original published paper. The units have been checked and are consistent.
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Circadian rhythms are sustained oscillations which arise spontaneously with a period of about 24 hours. They occurs in a wide range of living organisms, including cyanobacteria, plants, insects and mammals. Interestingly, these rhythms have been shown to be independent of environmental cues - for example they continue to occur even when an organism is maintained under conditions of continuous light or dark. During the past decade the molecular mechanisms underlying circadian rhythms have been intensely studied, across a range of organisms, including <emphasis>Drosophila</emphasis>, <emphasis>Neurospora</emphasis>, cyanobacteria, plants and mammals. Common to all these organisms, the molecular mechanisms underlying the circadian oscillations rely on negative feedback regulation of gene expression.
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<para>
The mechanism of circadian rhythms relies on interactions between negative and positive feedback loops (as shown in the figure below). The primary function of circadian rhythms is to allow organisms to adapt to their ever changing environment, which changes periodically on a 24 hour cycle. Although circadian rhythms are endogenous and can continue in the absence of environmental cues, light can entrain the cycle and in mammals it acts by enhancing the expression of the Per gene.
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<para>
In the paper described here, John Tyson <emphasis>et al.</emphasis> present a simple mathematical model of circadian rhythms based on the interactions and degradation of the protein products of two genes; <emphasis>period</emphasis> (<emphasis>per</emphasis>) and <emphasis>timeless</emphasis> (<emphasis>tim</emphasis>). Their model incorporates the regulatory effects of the PER and TIM protein heterodimer on gene expression (negative feedback loops), and also describes how the activity of these proteins is regulated post-translationally by their reversible phosphorylation. All this information is captured by a pair of nonlinear ordinary differential equations and a single algebraic equation, yet despite its simplicity the model is able to account for several natural features of circadian rhythms observed experimentally.
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<caption>Schematic diagram of a simple molecular mechanism for the circadian clock in <emphasis>Drosophila</emphasis> PER and TIM proteins are synthesised in the cytoplasm where they may either be degraded by proteolysis or alternatively they may combine to form relatively stable heterodimers. These complexes are then transported to the nucleus where they act to inhibit the transcription of <emphasis>per</emphasis> and <emphasis>tim</emphasis> mRNA.</caption>
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The complete original paper reference is cited below:
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<para>
A Simple Model of Circadian Rhythms Based on Dimerization and Proteolysis of PER and TIM, John J. Tyson, Christian I. Hong, C. Dennis Thron, and Bela Novak, 1999,<emphasis>Biophysical Journal</emphasis>, 77, 2411-2417. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10545344&query_hl=1&itool=pubmed_docsum">PubMed ID: 10545344</ulink>
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