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for Chinese hamster V 79 cells [Klevecz (1976)] and wee1 cdc25 ssion yeast cells
[Sveiczer et al. (1996)], among others.
The variability in the system behavior can be signicantly enhanced when the
network becomes slightly inhomogeneous (due for instance to dierent 1 values in
dierent cells) in the presence of noise. Another important eect that arises in this
system is the possibility to observe maximal variability for an optimal noise inten-
sity. This is in contrast to the well-known eect of coherence resonance [Pikovsky
and Kurths (1997)], where for intermediate noise intensities, maximal order can be
achieved in systems with underlying nonlinear dynamics [Koseska et al. (2007b)].
The results also show that, although organized in a population, dierent oscillators
are characterized by dierent ISI distributions, as a consequence of the specic,
repulsive coupling considered.
3.4. Conclusions and Discussion
The concept of synthetic genetic networks is becoming increasingly exploited as a
basic step to understand how cellular processes arise from the connectivity of genes
and proteins. The ability of these circuits to produce dierent rhythms, as has
been shown in this Chapter, could have important applications in functional ge-
nomics, gene and cell therapy, etc., since the multistability and multirhythmicity of
synthetic genetic networks leads to an extended functionality, improved adaptation
and ability to store information. On the other hand, one could more easily relate
dierent biological phenomena and extract functional conclusions by observing a
highly-adaptive synthetic genetic network, instead of a network producing a unied
rhythm.
Here we have reviewed the possibility to use a modular coupling mechanism
via quorum sensing, which leads to synchronization under realistic conditions in
an ensemble of existing synthetic repressilators. By its design, the communication
module can be added directly to existing repressilator strains and mimic natural
multicellular clocks that operate on mean periods resulting from averaging multiple
cells [Liu et al. (1997); Herzog et al. (1998); Honma et al. (1998); Nakamura et al.
(2001); Herzog et al. (2004)]. Besides its eciency, the synchronization reported
here has been seen to lead to the generation of a global rhythm in a highly het-
erogeneous ensemble of genetic oscillators. The resulting clock behavior is seen to
be highly robust to random phase drifts of the individual oscillators due to noise.
In the light of these results, one might speculate whether natural biological clocks
have evolved in this same way, i.e. by using inter-cell communication to couple an
assembly of originally independent sloppy clocks. The cell-to-cell communication
module can also be coupled with the individual genetic circuit in such a way that
coupling is phase-repulsive [Ullner et al. (2007)].
Beside its biological consequences and extended functionality, the coupling mech-
anism discussed here leads to new phenomena from a general nonlinear dynamics
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