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X-Machines for Agent-Based Modeling: FLAME Perspectives
putational model addressing multi-compartmentalization and how this
influences the dynamics of MAPK cascade activation. The model shows
that multi-compartmentalization coupled with periodic MAPK kinase
(MAPKK) activation may be critical factors for the emergence of oscillation and ultrasensitivity in the system. The model establishes a link
between the spatial arrangements of the cascade components and temporal activation mechanisms, and how both contribute to fidelity and
specificity of MAPK-mediated signalling.
Oxidase regulation in anaerobic E. Coli cells. In the presence of oxygen (O2) the model bacterium Escherichia coli can conserve energy by
aerobic respiration. Two major terminal oxidases are involved in this
process, (1) Cyo has a relatively low affinity for O2 but is able to pump
protons and hence is energetically efficient, and (2) Cyd has a high affinity for O2 but does not pump protons.
When E. coli encounters environments with different O2 availabilities,
the expression of the genes encoding the alternative terminal oxidases,
the cydAB and cyoABCDE operons, are regulated by two O2-responsive
transcription factors, ArcA (an indirect O2 sensor) and FNR (a direct
O2 sensor). It has been suggested that O2-consumption by the terminal
oxidases located at the cytoplasmic membrane significantly affects the
activities of ArcA and FNR in the bacterial nucleoid. In this study, the
agent-based modeling approach represented spatially the bacterial process and simulated the uptake and consumption of O2 by E. coli. It also
presented a consequent modulation of ArcA and FNR activities based on
experimental data obtained from highly controlled chemostat cultures.
The molecules of O2, transcription factors and terminal oxidases were
treated as individual agents and their behaviors with interactions were
imitated in a simulated 3D E. coli cell. The model implied that there
are two barriers that dampen the response of FNR to O2, i.e. consumption of O2 at the membrane by the terminal oxidases and reaction of
O2 with cytoplasmic FNR. Analysis of FNR variants suggested that the
monomer-dimer transition is the key step in FNR-mediated repression
of gene expression [17].
Blood-brain barrier and nanoparticles. Blood mediated nanoparticle
delivery is a new and growing field in the development of therapeutics
and diagnostics. Nanoparticle properties such as size, shape and surface
chemistry can be controlled to improve their performance in biological systems. This enables modulation of immune system interactions,
blood clearance profile and interaction with target cells, thereby aiding
effective delivery of cargo within cells or tissues. Their ability to target
and enter tissues from the blood is highly dependent on their behavior
under blood flow. Here, the modelers produced an agent-based model
of nanoparticle behavior under blood flow in capillaries. They demonstrated that red blood cells are highly important for effective nanopar-
X-Machines for Agent-Based Modeling: FLAME Perspectives
putational model addressing multi-compartmentalization and how this
influences the dynamics of MAPK cascade activation. The model shows
that multi-compartmentalization coupled with periodic MAPK kinase
(MAPKK) activation may be critical factors for the emergence of oscillation and ultrasensitivity in the system. The model establishes a link
between the spatial arrangements of the cascade components and temporal activation mechanisms, and how both contribute to fidelity and
specificity of MAPK-mediated signalling.
Oxidase regulation in anaerobic E. Coli cells. In the presence of oxygen (O2) the model bacterium Escherichia coli can conserve energy by
aerobic respiration. Two major terminal oxidases are involved in this
process, (1) Cyo has a relatively low affinity for O2 but is able to pump
protons and hence is energetically efficient, and (2) Cyd has a high affinity for O2 but does not pump protons.
When E. coli encounters environments with different O2 availabilities,
the expression of the genes encoding the alternative terminal oxidases,
the cydAB and cyoABCDE operons, are regulated by two O2-responsive
transcription factors, ArcA (an indirect O2 sensor) and FNR (a direct
O2 sensor). It has been suggested that O2-consumption by the terminal
oxidases located at the cytoplasmic membrane significantly affects the
activities of ArcA and FNR in the bacterial nucleoid. In this study, the
agent-based modeling approach represented spatially the bacterial process and simulated the uptake and consumption of O2 by E. coli. It also
presented a consequent modulation of ArcA and FNR activities based on
experimental data obtained from highly controlled chemostat cultures.
The molecules of O2, transcription factors and terminal oxidases were
treated as individual agents and their behaviors with interactions were
imitated in a simulated 3D E. coli cell. The model implied that there
are two barriers that dampen the response of FNR to O2, i.e. consumption of O2 at the membrane by the terminal oxidases and reaction of
O2 with cytoplasmic FNR. Analysis of FNR variants suggested that the
monomer-dimer transition is the key step in FNR-mediated repression
of gene expression [17].
Blood-brain barrier and nanoparticles. Blood mediated nanoparticle
delivery is a new and growing field in the development of therapeutics
and diagnostics. Nanoparticle properties such as size, shape and surface
chemistry can be controlled to improve their performance in biological systems. This enables modulation of immune system interactions,
blood clearance profile and interaction with target cells, thereby aiding
effective delivery of cargo within cells or tissues. Their ability to target
and enter tissues from the blood is highly dependent on their behavior
under blood flow. Here, the modelers produced an agent-based model
of nanoparticle behavior under blood flow in capillaries. They demonstrated that red blood cells are highly important for effective nanopar-