Biology Reference
In-Depth Information
CHAPTER
activity in Bacillus subtilis
1
Eric Botella
*
,1
, David Noone
*
, Letal I. Salzberg
*
, Karsten Hokamp
*
, Susanne Krogh
Devine
*
, Mark Fogg
{
, Anthony J. Wilkinson
{
, Kevin M. Devine
*
,1
⁎
Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
{
Structural Biology Laboratory, Department of Chemistry, University of York, York,
United Kingdom
1
Corresponding authors. e-mail address: botellae@tcd.ie; kdevine@tcd.ie
High-resolution temporal
analysis of global promoter
1
INTRODUCTION
Until recently, the reductionist approach predominated in biological research. Its
objectives were to describe and understand a biological entity in terms of its sub-
systems, their constituent components and the molecular interactions both within
and between them. This approach emerged from the prevailing technological capa-
bilities, whereby single or small numbers of molecules and the interactions between
them could be described in great detail. However, this approach is limited in that
even the simplest biological system is highly complex, composed of a myriad of
subsystems and their constituent components that interact in a highly precise and
regulated way. A key concept of such systems is emergence: the idea that integration
of the subsystems leads to the emergence of novel properties and characteristics that
cannot be predicted from the analysis of the individual constituent parts. Just as the
functioning and uses of a car cannot be adequately described or understood in terms
of its constituent parts and subsystems, so it is that understanding a biological system
requires a more global and holistic approach to reveal novel characteristics. To some
extent, “life” is the emergent property of the sum of the components and specific
interactions that occur in the cell or organism. It is evident that global approaches
are required to better describe biological systems and how they change in response
to alterations in the prevailing conditions.
A key objective, therefore, is to establish the regulatory circuitry and dynamics of
gene expression at a global level. Many attributes of the regulatory circuitry can be
deduced from the changes that occur in cellular RNA profiles in response to diverse
stimuli. Techniques such as RNA-Seq and high-density microarrays give a very
detailed static view of the spectrum of cellular RNA species and their prevalence
at any particular time point, from which many features of the regulatory network
can be inferred (
Chechik
et al.
, 2008; Chechik and Koller, 2009; Ralser
et al.
,
2009
). However, the complexity and cost of RNA-Seq and microarrays makes them
