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Systems biology aims to describe and to understand the operation of complex biological systems with the goal of developing predictive models of human disease. The most powerful systems biology approaches would ideally integrate information from (1) large datasets of gene, protein, and metabolite measurement ("omics" data), (2) complex cell- and tissue-level in vitro models of the disease...
Systems biology aims to describe and to understand the operation of complex biological systems with the goal of developing predictive models of human disease. The most powerful systems biology approaches would ideally integrate information from (1) large datasets of gene, protein, and metabolite measurement ("omics" data), (2) complex cell- and tissue-level in vitro models of the disease...
We describe the development of a very large-scale causal, computable model of biology and its specific application in the identification of molecular cause and effect hypotheses of mechanisms underlying the effects of androgen stimulation in the LNCaP prostate carcinoma cell line. In contrast to previous LNCaP studies in which genes have been hierarchically clustered by their pattern of response to...
We describe the development of a very large-scale causal, computable model of biology and its specific application in the identification of molecular cause and effect hypotheses of mechanisms underlying the effects of androgen stimulation in the LNCaP prostate carcinoma cell line. In contrast to previous LNCaP studies in which genes have been hierarchically clustered by their pattern of response to...
In breast cancer treatment for many cases intrinsic or acquired resistance against available therapeutics leads to death. According to the present biological understanding, drug resistance is caused by molecular mechanisms in the complex network of proteins that regulate cell proliferation by activation of the estrogen receptor (ER), hereby allowing the cell to bypass the classical estrogen receptor...
In breast cancer treatment for many cases intrinsic or acquired resistance against available therapeutics leads to death. According to the present biological understanding, drug resistance is caused by molecular mechanisms in the complex network of proteins that regulate cell proliferation by activation of the estrogen receptor (ER), hereby allowing the cell to bypass the classical estrogen receptor...
It has been appreciated for at least a hundred years that biological organisms contain control systems that enable them to adapt to a changing environment and adjust their internal systems when they need to proliferate. Even so, we have little understanding of the role that many of the control systems play. It's only in recent years that mainstream science has begun to study biological systems qualitatively...
It has been appreciated for at least a hundred years that biological organisms contain control systems that enable them to adapt to a changing environment and adjust their internal systems when they need to proliferate. Even so, we have little understanding of the role that many of the control systems play. It's only in recent years that mainstream science has begun to study biological systems qualitatively...
Signal transduction mediated by protein phosphorylation regulates many cellular biological processes. In order to effectively monitor protein phosphorylation events governing signaling cascades, we have developed a methodology enabling the simultaneous quantification of tyrosine phosphorylation of specific residues on dozens of key proteins in a time-resolved manner. In our initial implementation,...
Signal transduction mediated by protein phosphorylation regulates many cellular biological processes. In order to effectively monitor protein phosphorylation events governing signaling cascades, we have developed a methodology enabling the simultaneous quantification of tyrosine phosphorylation of specific residues on dozens of key proteins in a time-resolved manner. In our initial implementation,...
Signal transduction networks are often described by qualitative models that incorporate experimental findings from different cell types. However, a large body of evidence suggests that cell signaling differs substantially from one cell type to the next. Even in cases in which the topology of signaling networks is conserved, different cell types respond differently under the same experimental conditions...
Signal transduction networks are often described by qualitative models that incorporate experimental findings from different cell types. However, a large body of evidence suggests that cell signaling differs substantially from one cell type to the next. Even in cases in which the topology of signaling networks is conserved, different cell types respond differently under the same experimental conditions...
Contrast-enhanced magnetic resonance imaging (MRI) is useful to study the infiltration of immune cells, in particular macrophages. Contrast agents, for example ultra-small superparamagnetic iron oxide (USPIO) particles, administered intravenously into the blood stream will be engulfed by macrophages circulating in the circulation system. When a transplanted heart rejects, macrophages and other immune...
The molecular circadian clock which is present in almost all cells of animal organisms exerts a control on the cell division cycle in proliferating tissues by modulating the activity of cyclins and cyclin dependent kinases (CDKs), the proteins which determine transitions from one phase of the cell cycle to the following one, until effective division. Each peripheral cell circadian clock is under the...
The molecular circadian clock which is present in almost all cells of animal organisms exerts a control on the cell division cycle in proliferating tissues by modulating the activity of cyclins and cyclin dependent kinases (CDKs), the proteins which determine transitions from one phase of the cell cycle to the following one, until effective division. Each peripheral cell circadian clock is under the...
The processing components and the dynamic signaling network that an individual cell uses to do signal integration and make decisions based on multiple sensory inputs are being identified in a well studied free-swimming unicellular green algal model organism, Chlamydomonas. It has many sensory photoreceptors and measurable behavior associated with its orienting and swimming with respect to light sources...
The processing components and the dynamic signaling network that an individual cell uses to do signal integration and make decisions based on multiple sensory inputs are being identified in a well studied free-swimming unicellular green algal model organism, Chlamydomonas. It has many sensory photoreceptors and measurable behavior associated with its orienting and swimming with respect to light sources...
Here we show how nonlinear system identification techniques, such as fast orthogonal search (FOS) and the orthogonal search method (OSM), can be used to analyze gene expression profiles and predict the class to which a profile belongs
Here we show how nonlinear system identification techniques, such as fast orthogonal search (FOS) and the orthogonal search method (OSM), can be used to analyze gene expression profiles and predict the class to which a profile belongs
A mathematical model of whole-body metabolism is developed to predict glucose homeostasis during exercise by using a hormonal controller over cellular metabolic processes. Model simulations were validated with experimental data from exercise studies in humans. The exercise-induced changes in hormonal signals modulated metabolic flux rates of various tissues in a coordinated way to maintain blood glucose...
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