Temporal Partitioning of the Yeast Cellular Network - Systems Biology of Metabolic and Signaling Networks - page 315

tin dynamics. Ultimately, anabolism and catabolism become globally partitioned:
mediation is by direct feedback loops between the energetic and redox state of the
cell and chromatin architecture via enzymatic co-factors and co-enzymes.
Multi-oscillatory outputs were observed in dissolved gases with 12-h, 40-min
and 4-min periods, and statistical self-similarity in Power Spectral and Relative
Dispersional analyses: i.e. complex non-linear behaviour and a functional scale-
free network operating simultaneously on several timescales. Fast sampling (at 10
or 1 Hz) of NAD(P)H fluorescence revealed subharmonic components of the
40-min signal at 20,10 and 3-5 min. The latter corresponds to oscillations directly
observed and imaged by 2-photon microscopy in surface-attached cells. Signalling
between time domains is suggested by studies with protonophore effectors of
mitochondrial energetics. Multi-oscillatory states impinge on the complex
reactome (where concentrations of most chemical species oscillate) and network
functionality is made more comprehensible when in vivo time structure is taken
into account.

12.1 Temporal Aspects of Integrative Yeast Cellular
Function

Whereas our appreciation of the importance of spatial relationships between the
myriad molecular components of living systems is well developed, temporal
aspects of cell organisation are somewhat neglected. The intricate coordination of
reactions, processes and events required during the life of the cell necessitates
understanding across and between multiple timescales. Thus, it is not sufficient to
consider only the slow process of growth and division (or budding in the case of
Saccharomyces cerevisiae ), the most evident as observed by simple light micros-
copy and taking a matter of hours (Lloyd et al. 1982b ), but we must account for the
integration of events from the membrane-associated biophysical domain (

μ

s-ms),
up through the metabolic timescale (seconds), the biosynthesis of macromolecules,
transcription and translation (minutes), to assembly and remodelling of organelles
(Aon and Cortassa 1997 ). Whereas spatio-temporal coincidence, convergence and
simultaneity are often evident functional necessities, separation of incompatible
processes must also be accommodated (Lloyd and Rossi 1992 , 2008 ; Lloyd 2006a ,
2008 ; Sasidharan et al. 2012 ).
Although as a matter of convenience and ease of study, the different time
domains have been considered and researched as being separate; the resulting
concept of hierarchical organisation is a misleading oversimplification. Interactions
between faster and slower processes result in a heterarchical system (Yates 1992 ;
Murray et al. 2007 ).