- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 16:06:58+12:00
- Desc:
- committing version01 of sriram_bernot_kepes_2007
- Permanent Source URI:
- http://models.cellml.org/workspace/sriram_bernot_kepes_2007/rawfile/46cc7d0d1594df7a28ff5a86649e81d71be6512e/sriram_bernot_kepes_2007.cellml
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This CellML file was generated on 11/02/2009 at 3:06:39 at p.m. using:
COR (0.9.31.1125)
Copyright 2002-2009 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
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http://www.CellML.org/
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<article>
<articleinfo>
<title>A minimal mathematical model combining several regulatory cycles from the budding yeast cell cycle</title>
<author>
<firstname>Jeelean</firstname>
<surname>Lim</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML version of the model has been checked in COR and PCEnv and the model runs to replicate the original published results as depicted in figure 12 of the paper. The units have been checked and are consistent.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: A novel topology of regulatory networks abstracted from the budding yeast cell cycle is
studied by constructing a simple nonlinear model. A ternary positive feedback loop with only
positive regulations is constructed with elements that activates the subsequent element in a clockwise
fashion. A ternary negative feedback loop with only negative regulations is constructed with
the elements that inhibit the subsequent element in an anticlockwise fashion. Positive feedback
loop exhibits bistability, whereas the negative feedback loop exhibits limit cycle oscillations.
</para>
<para>
The novelty of the topology is that the corresponding elements in these two homogeneous feedback
loops are linked by the binary positive feedback loops with only positive regulations. This
results in the emergence of mixed feedback loops in the network that displays complex behaviour
like the coexistence of multiple steady states, relaxation oscillations and chaos. Importantly, the
arrangement of the feedback loops brings in the notion of checkpoint in the model.
</para>
<para>
The model
also exhibits domino-like behaviour, where the limit cycle oscillations take place in a stepwise
fashion. As the aforementioned topology is abstracted from the budding yeast cell cycle, the
events that govern the cell cycle are considered for the present study. In budding yeast, the
sequential activation of the transcription factors, cyclins and their inhibitors form mixed feedback
loops. The transcription factors that involve in the positive regulation in a clockwise orientation
generates ternary positive feedback loop, while the cyclins and their inhibitors that involve in the
negative regulation in an anticlockwise orientation generates ternary negative feedback loop. The
mutual regulation between the corresponding elements in the transcription factors and the cyclins
and their inhibitors generates binary positive feedback loops.
</para>
<para>
The bifurcation diagram constructed for the whole system can be related to the different events of the cell cycle in terms of dynamical
system theory. The checkpoint mechanism that plays an important role in different phases of the cell cycle are accounted for by silencing appropriate feedback loops in the model.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://ieeexplore.ieee.org/ielx5/4100185/4317450/04317452.pdf?arnumber=4317452">A minimal mathematical model combining several regulatory cycles from the budding yeast cell cycle</ulink>, K. Sriram, G. Bernot and F. Kepes, 2007, <ulink url="www.ietdl.org/IET-SYB">
<emphasis>IET systems biology</emphasis>
</ulink>, 1, 326-341. (A PDF version of the article is available online.) <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/18203579">PubMed ID: 18203579</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
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<title>figure 1</title>
</objectinfo>
<imagedata fileref="sriram_2007a.png"/>
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<caption>Common feedback loops studied in the biological systems</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
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<title>figure 2</title>
</objectinfo>
<imagedata fileref="sriram_2007b.png"/>
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<caption>Regulatory networks of homogeneous and mixed feedback loops</caption>
</informalfigure>
</sect1>
</article>
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