Nonlinear Dyn
https://doi.org/10.1007/s11071-018-4215-0
ORIGINAL PAPER
Mathematical modelling of nonlinear dynamics generated
from modular interconnections in cellular SOS response
system
Silpa Bhaskaran · Achuthsankar S. Nair
Received: 13 June 2017 / Accepted: 17 March 2018
© Springer Science+Business Media B.V., part of Springer Nature 2018
Abstract Nonlinear dynamics in synthetic biology
systems, generated as a consequence of interconnec-
tions between biological modules, poses challenges to
the objective of engineering biological systems with
predictable characteristics. Mathematical models, that
often provide accurate descriptions of the biological
modules in isolation, fail to capture such nonlineari-
ties that arise in the interconnected modules. Without
the modelling and quantification of these nonlineari-
ties, systems biology models cannot be predictable or
reliable. Hence it become a key area of focus of sys-
tems and synthetic biologists. To this end, we anal-
yse the nonlinearities in the SOS response system, a
prime cellular network in bacterial cells that functions
to repair the DNA damage. It is shown that the dynam-
ics of the modules in the SOS response system differ in
isolation and in integration, and substantial variation is
observed when more modules are connected. The inter-
dependence among major modules is quantified, which
imparts whether the integrated dynamics is an attenu-
ation or amplification of the isolated dynamics. From
a synthetic biology perspective, our study contributes
to the effective engineering of biological devices from
the integration of biological modules in a bottom-up
fashion. Meanwhile, it also complements the investi-
gations on the DNA damage repairing mechanism in
living cells.
S. Bhaskaran (B ) · A. S. Nair
Department of Computational Biology and Bioinformatics,
University of Kerala, Trivandrum, India
e-mail: silpabhaskaran@gmail.com
Keywords Biological networks · Modularity · SOS
response system · Dynamics · Cascaded layering
framework · Functionality · Mutual dynamics ·
Synthetic biology
1 Introduction
Dynamic behaviour of biological networks is a key
topic of investigation for systems and synthetic biolo-
gists, as it helps in their efforts on engineering a living
cell with predictable characteristics. Elucidation of the
network dynamics enables them to probe into the basic
design principles of living systems. These insights can
be applied to the designing of novel biological systems
or to the redesigning of existing biological systems for
novel applications, with the help of mathematical mod-
els and engineering principles.
Adopting the modular approach for the engineering
of artificial systems, biological systems are also often
designed and fabricated in a hierarchical manner. The
small and simple modules are redesigned and engi-
neered initially which are integrated with each other
to form the higher level of systems. With this objec-
tive, several biological modules have been modelled
and analysed by the systems biologists. These mod-
ules, in turn, have been engineered and incorporated
into living cells by the synthetic biologists, so that they
exhibited the characteristics they have been looking for.
The successful engineering of the repressilator by [1]
and the toggle switch by [2] is the pioneering work
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