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Boolean models of the fission yeast cell-cycle in two yeast species reveals their
difference in circuitry and dynamics. While the
S. cerevisiae
system operates in a
strongly damped mode, driven by external excitation, the
S. pombe
network
represents an auto-excited system with external damping (Davidich
et al
. 2008).
Immunology:
In immunology the interplay between various immune
components such as cytokines and cells is crucial in deciding the outcome of
the immune response against a particular pathogen. While gene regulatory
networks determine cell types and signal transduction networks determine the
response of particular cell types to cytokines, the interplay between different
immune components decide the particular gene regulatory networks and signal
transduction networks that will be activated. We will expand here on a Boolean
model of the immune response against a bacterial pathogen in which diverse
components describing interactions at different scales are assembled into a
network. The immune response involves activation of various components
such as immune cells, signaling molecules called cytokines and proteins such
as complement. We have studied the activation of immune components and
their regulation in response to respiratory pathogens of genus
Bordetella
(Thakar
et al
. 2007) by using an asynchronous Boolean model. We particularly
compared the immune response to two pathogens,
B. bronchiseptica
and
B. pertussis
.
B. pertussis
is the causative agent of whooping cough in humans
and has evolved from a
B. bronchiseptica
like progenitor. Nevertheless,
B.
bronchiseptica
and
B.
pertussis
have different host ranges and cause different
diseases in their hosts. These pathogens can modulate the host immune response
leading to their establishment and persistence in the host.
Immunologists for long time have focused on characterizing the immune
responses in terms of activation of immune components in response to pathogens,
for example activation of IL10 in response to the type III secretion system of
B. bronchiseptica
, or clearance of bacteria followed by activation of T helper 1
(Th1) cells. Thus, there is a lot of qualitative data available in immunology which
awaits a formal mathematical description. We developed the asynchronous
Boolean model using independent timescales for each process in the network.
The model was augmented by using experimental information on the time scales
of activation of some of the processes so that the timing of the update of a few
nodes was fixed and the order of update of all other nodes was randomly chosen.
We also designed two modifications of the classical Boolean functions, a
threshold on the number of consecutive steps of phagocytosis in order to clear
bacteria, and
decay of cytokines and bacterial virulence factors, even in the
presence of their regulators, after an individually chosen interval.
