MINIREVIEW SERIES

Cell dynamics and the onset of collective behaviourin gene regulationAlessandro Giuliani

Environment and Health Department, Istituto Superiore di Sanita, Rome, Italy

Dynamical processes involving more-or-less periodical

oscillations of relevant physiological parameters occur

in cell cultures, however, much of the success in molec-

ular genetics has been achieved by setting aside the

possible existence of collective organized behaviour in

cultured cells. Cell cultures are often considered ergo-

dic ensembles of independent units (cells), randomly

scattered in different phases of their biological cycle,

and results are attributed to a sort of ‘average cell’.

The recent discovery of very reliable and stable met-

abolic cycles in cultured cells has led to an abrupt

change in perspective, forcing us to take into consider-

ation the multifaceted implications of dealing with

strongly nonergodic systems in which cell populations

can no longer be regarded as a random collection of

noninteracting individuals, but rather as organized

systems of interacting oscillators. These oscillators

seem to work at all levels of cellular organization from

gene expression to protein production and metabolism.

How do these multiple oscillators interlock and how

do they correlate with the cell-division cycle? The

answers to these questions will surely have a deep

impact on our appreciation of cell physiology and on

the development of therapeutic strategies for many

different diseases.

In this minireview series, this issue is approached via

three different, but complementary, avenues. Bianchi

gives us an appreciation of the ‘metabolic side’ of cell

dynamics; with special emphasis on the microbial

world, both in culture and in the natural environment,

all the main known biochemical cycles are considered,

analysing both their biochemical bases and their rele-

vance to the adaptation of micro-organisms to their

environment. Palumbo et al. focus on the role of post-

transcriptional regulation in the establishment of

genome-scale gene-expression cycles. The authors try to

complement the classical molecular biology approach

with a system-engineering view. Klevecz et al. present a

vivid reconstruction of the general implications

involved in the dynamical perspective of cell biology;

they explain why considering the cell as a dynamical

attractor sheds a completely new light on our interpre-

tations of many different experimental facts ranging

from cell-cycle regulation to the effects of drugs.

Overall, the goal of this minireview series is to focus

attention on the fast-developing field of cell dynamics,

highlighting both the theoretical and practical conse-

quences of paying serious attention to a temporal

perspective in cell biology.

Alessandro Giuliani graduated in biology from the University of Rome ‘La Sapienza’ and then specialized in sta-

tistics at the same university. Since 1997 he has worked in the Istituto Superiore di Sanita as a senior scientist.

His research focuses on the quantitative modelling of biology with a special emphasis on multidimensional sta-

tistical methods, which he considers most suited for dealing with complex systems. He has published more

than 150 papers in the peer-reviewed literature ranging from psychobiology to protein science, ecology, nonlin-

ear dynamics, epidemiology, biochemistry and physiology.

doi: 10.1111/j.1742-4658.2008.06396.x

FEBS Journal 275 (2008) 2355 ª 2008 The Author Journal compilation ª 2008 FEBS 2355