48,899 research outputs found
Mathematical modelling plant signalling networks
During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This sub-cellular analysis paves the way for more comprehensive mathematical studies of hormonal transport and signalling in a multi-scale setting
The computer revolution in science: steps towards the realization of computer-supported discovery environments
The tools that scientists use in their search processes together form so-called discovery environments. The promise of artificial intelligence and other branches of computer science is to radically transform conventional discovery environments by equipping scientists with a range of powerful computer tools including large-scale, shared knowledge bases and discovery programs. We will describe the future computer-supported discovery environments that may result, and illustrate by means of a realistic scenario how scientists come to new discoveries in these environments. In order to make the step from the current generation of discovery tools to computer-supported discovery environments like the one presented in the scenario, developers should realize that such environments are large-scale sociotechnical systems. They should not just focus on isolated computer programs, but also pay attention to the question how these programs will be used and maintained by scientists in research practices. In order to help developers of discovery programs in achieving the integration of their tools in discovery environments, we will formulate a set of guidelines that developers could follow
A self-organized model for cell-differentiation based on variations of molecular decay rates
Systemic properties of living cells are the result of molecular dynamics
governed by so-called genetic regulatory networks (GRN). These networks capture
all possible features of cells and are responsible for the immense levels of
adaptation characteristic to living systems. At any point in time only small
subsets of these networks are active. Any active subset of the GRN leads to the
expression of particular sets of molecules (expression modes). The subsets of
active networks change over time, leading to the observed complex dynamics of
expression patterns. Understanding of this dynamics becomes increasingly
important in systems biology and medicine. While the importance of
transcription rates and catalytic interactions has been widely recognized in
modeling genetic regulatory systems, the understanding of the role of
degradation of biochemical agents (mRNA, protein) in regulatory dynamics
remains limited. Recent experimental data suggests that there exists a
functional relation between mRNA and protein decay rates and expression modes.
In this paper we propose a model for the dynamics of successions of sequences
of active subnetworks of the GRN. The model is able to reproduce key
characteristics of molecular dynamics, including homeostasis, multi-stability,
periodic dynamics, alternating activity, differentiability, and self-organized
critical dynamics. Moreover the model allows to naturally understand the
mechanism behind the relation between decay rates and expression modes. The
model explains recent experimental observations that decay-rates (or turnovers)
vary between differentiated tissue-classes at a general systemic level and
highlights the role of intracellular decay rate control mechanisms in cell
differentiation.Comment: 16 pages, 5 figure
Designer Gene Networks: Towards Fundamental Cellular Control
The engineered control of cellular function through the design of synthetic
genetic networks is becoming plausible. Here we show how a naturally occurring
network can be used as a parts list for artificial network design, and how
model formulation leads to computational and analytical approaches relevant to
nonlinear dynamics and statistical physics.Comment: 35 pages, 8 figure
Systems biology in animal sciences
Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed ‘omics’ technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A ‘system’ approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with ‘system approaches’ in animal sciences, providing exciting opportunities to predict and modulate animal traits
Modeling sRNA-regulated Plasmid Maintenance
We study a theoretical model for the toxin-antitoxin (hok/sok) mechanism for
plasmid maintenance in bacteria. Toxin-antitoxin systems enforce the
maintenance of a plasmid through post-segregational killing of cells that have
lost the plasmid. Key to their function is the tight regulation of expression
of a protein toxin by an sRNA antitoxin. Here, we focus on the nonlinear nature
of the regulatory circuit dynamics of the toxin-antitoxin mechanism. The
mechanism relies on a transient increase in protein concentration rather than
on the steady state of the genetic circuit. Through a systematic analysis of
the parameter dependence of this transient increase, we confirm some known
design features of this system and identify new ones: for an efficient
toxin-antitoxin mechanism, the synthesis rate of the toxin's mRNA template
should be lower that of the sRNA antitoxin, the mRNA template should be more
stable than the sRNA antitoxin, and the mRNA-sRNA complex should be more stable
than the sRNA antitoxin. Moreover, a short half-life of the protein toxin is
also beneficial to the function of the toxin-antitoxin system. In addition, we
study a therapeutic scenario in which a competitor mRNA is introduced to
sequester the sRNA antitoxin, causing the toxic protein to be expressed.Comment: 25 pages, 8 figure
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