- Author:
- Geoff Nunns <gnunns1@jhu.edu>
- Date:
- 2010-04-27 15:26:42+12:00
- Desc:
- Added titles for each different variant in RDF.
- Permanent Source URI:
- https://models.cellml.org/workspace/leloup_gonze_goldbeter_1999/rawfile/9007a750bf5f9825140cbe9f67b0e7fa1af09dbc/leloup_gonze_goldbeter_1999_a.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : leloup_model_1999.xml
CREATED : 24th September 2003
LAST MODIFIED : 24th September 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Leloup et al.'s 1999 mathematical model of circadian rhythms in Drosophila.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#" cmeta:id="leloup_gonze_goldbeter_1999_version01" name="leloup_gonze_goldbeter_1999_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Limit Cycle Model for Circadian Rhythms in Drosophila and Neurospora</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This model has been curated and is known to reproduce the published results in COR and PCEnv. Some initial conditions have been corrected in this third version of the model. Thank you to Dagmar Kohn for her help in identifying the inconsistencies between the published paper and the CellML model.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Many living organisms, from bacteria to plants, insects to mammals, display circadian rhythms. These are spontaneously sustained oscillations with a period close to 24 hours. Even in the absence of environment cues, such as the light changes associated with day and night, organisms have been shown to retain their circadian behaviour, therefore suggesting that the rhythms are endogenous. Experiments with <emphasis>Drosophila</emphasis> (fruit fly), <emphasis>Neurospora</emphasis> (fungus), cyanobacteria, plants and mammals have improved our understanding of the molecular mechanisms underlying circadian rhythms. It seems that they rely on a negative feedback on gene expression. A number of genes involved in circadian rhythms have been identified. These include two which are considered in the current model: <emphasis>Per</emphasis> (period) and <emphasis>Tim</emphasis> (timeless).
</para>
<para>
In order to better understand the genetic mechanisms underlying the regulation of rhythms, scientists have developed mathematical models of the oscillatory periods. Initially, these models described ultradian (less than 24 hour period) oscillations, which are typically characterised by periods from seconds to minutes. These early molecular models predicted that negative feedback on gene expression generated the limit cycles. This principle was subsequently applied to the study of circadian rhythms. During the past decade, improved experimental techniques have lead to the elucidation of much genetic and biochemical data relating to mechanisms controlling circadian rhythms. Concurrent with this increase in data availability, more detailed theoretical models can be developed.
</para>
<para>
In this 1999 study, Leloup <emphasis>et al.</emphasis> develop mathematical models of the genetic regulation underlying circadian oscillations in <emphasis>Drosophila</emphasis> and <emphasis>Neurospora</emphasis>. Experimental observations indicate that a similar genetic control underlies circadian rhythm generation in both <emphasis>Drosophila</emphasis> and <emphasis>Neurospora</emphasis>. In each case, circadian oscillations arise from the negative autoregulation of gene expression (see <xref linkend="fig_reaction_diagram1"/> and <xref linkend="fig_reaction_diagram2"/> below). In <emphasis>Drosophila</emphasis>, a PER-TIM protein complex migrates to the nucleus and represses the transcription of the <emphasis>per</emphasis> and <emphasis>tim</emphasis> genes. Similarly in <emphasis>Neurospora</emphasis>, FRQ protein enters the nucleus where it represses the transcription of its gene <emphasis>frq</emphasis>. Together with the negative, autoregulatory feedback loops just discussed, the models also take into account the specific effects of light in these two systems. In <emphasis>Drosophila</emphasis>, light controls the circadian rhythm by inducing the degeneration of TIM. In <emphasis>Neurospora</emphasis>, light controls the circadian system by inducing the transcription of <emphasis>frq</emphasis>.
</para>
<para>
The model has been described here in CellML (the raw CellML description of the Leloup <emphasis>et al.</emphasis> 1999 model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Limit Cycle Models for Circadian Rhythms Based on Transcriptional Regulation in <emphasis>Drosophila</emphasis> and <emphasis>Neurospora</emphasis>, Jean-Christophe Leloup, Didier Gonze, and Albert Goldbeter, 1999, <emphasis>Journal of Biological Rhythms</emphasis>, 14, 433-448. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10643740&dopt=Abstract">PubMed ID: 10643740</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram1">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram1</title>
</objectinfo>
<imagedata fileref="leloup_1999.png"/>
</imageobject>
</mediaobject>
<caption>Scheme for the model for circadian oscillations in <emphasis>Drosophila</emphasis> involving negative regulation of gene expression by the PER-TIM protein complex. And beneath this is the scheme for the model for circadian rhythms in <emphasis>Neurospora</emphasis>. This model is based on negative feedback exerted by the protein FRQ on the transcription of the <emphasis>frq</emphasis> gene.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<vCard:Given>James</vCard:Given>
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