Biology Reference
In-Depth Information
Chapter 18
Yeast Systems Biology: Towards
a Systems Understanding of Regulation
of Eukaryotic Networks in Complex
Diseases and Biotechnology
Juan I. Castrillo, Pinar Pir and Stephen G. Oliver
Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road,
Cambridge CB2 1GA, UK
Chapter Outline
Introduction
343
Comprehensive Data Analysis and Integration
Methods: State-of-the-Art
Yeast for Systems Understanding of Eukaryotic Biology
and Networks Applications
348
344
Towards Comprehensive Integration of 'Omics'
Datasets from Single Experiments
Yeast as a Model System for Comprehensive Systems
Biology Studies
351
344
Yeast for Comprehensive Studies of Dynamics of
Dysregulated Networks: Towards Rational Strategies and
Applications in Biotechnology and Human Disease
Data Analysis and Integration for Systems Biology Studies:
State-of-the-art Towards Comprehensive Integration of
'Omics' Datasets
353
346
Conclusions: Future Perspectives
357
Need for a Clear Definition of Objectives
and Experimental Design
Acknowledgements
357
346
References
357
Experimental Systems for Comprehensive Studies of
Yeast Networks Dynamics: from Steady States to Time-
Course Experiments through Perturbations
347
INTRODUCTION
In February 2001, Nature and Science published two
landmark papers which provided the first draft of the
human genome sequence
[1,2]
. More than 10 years
later, we are still far from understanding the exquisite
complexity of human biology
[3
10% of all potential human regulatory protein
protein
e
interactions
[13,14]
.
We are far fromunderstanding not only the complexity of
human biology, but also that of the eukaryotic cell and
its basic mechanisms of adaptation and evolution
[15
8]
.Manymore
initiatives to characterize human genetic and structural
variations are being developed (e.g., the 1000 Genomes
Project [
5,9,10
] and human metabolic networks are
being carefully reconstructed and refined
[11,12]
.
Moreover, it is clear that an increase in the limited
coverage of human regulatory networks is required. As
an example, current estimates
e
21]
.
'Nothing makes sense in biology except in the light of
evolution'
[21]
. The architecture and complexity of a bio-
logical system (e.g., single-celled, free-living prokaryote or
eukaryote; parasite
e
host, or multicellular system) and its
response to specific perturbations (e.g., disease) will always
have to be contemplated in the light of evolution
[16
e
19,22]
.
At this point, the humble yeast Saccharomyces cerevisiae,
with its molecular mechanisms, biological networks and
e
indicate that actual
protein
protein interaction maps may cover less than
e
