Biology Reference
In-Depth Information
Chapter 16
System Biology of Cell Signaling
Chiara Mariottini and Ravi Iyengar
Department of Pharmacology and Systems Therapeutics and Systems Biology Center, New York Mount Sinai School of Medicine,
New York, NY 10029, USA
Chapter Outline
Introduction
311
Network Topology and Consolidation of Signals
318
Cellular Signaling: Pathways to Networks
311
Dynamical Models
319
Isoforms of Signaling Molecules, Signaling Integration
and Sorting
Positive Feedback Loops can form Switches: The Concept
of Bistability
313
319
Scaffolding Proteins: Signaling Networks Form Signaling
Complexes
Signaling Microdomains Within Cells
322
314
Conclusions and Future Challenges
323
Computational Analysis of Signaling Networks
316
Glossary
324
Graph Theory-Based Models
316
Acknowledgments
324
Regulation By Network Motifs
316
References
324
Properties of a Cellular Signaling Network
317
Advances in experimental technologies that enable
large-scale survey-type experiments, genome-wide studies
such as whole genome sequencing
[4,5]
, microarrays
[6,7]
and RNAseq profiling
[8
'Every object that biology studies is a system of systems.'
Francois Jacob (1974)
13]
have greatly increased in number during the past decade.
Studies in molecular biology have increasingly adopted
a systems-based approach to obtaining and processing
high-throughput data and building computational models of
cellular systems made up of multiple interacting compo-
nents. Informatics research in systems biology is also
developing approaches to catalog and process information
in the extensive experimental biomedical research literature
that has focused on studying individual cellular compo-
nents in depth over the past five decades. Integrating
detailed knowledge of individual components and interac-
tions from earlier studies and contemporary experiments
will allow us to obtain a mechanistic understanding of how
components enable systems-level behaviors. Indeed,
a grand challenge in systems biology is to develop detailed
predictive models of mammalian cells.
10]
and proteomics
[11
e
e
INTRODUCTION
It is intuitively obvious that a system is an entity made up of
parts. This general definition is applicable to biological
entities across all scales of organization. An approach to
study systems is to consider them as networks of mutually
dependent and thus interconnected components that
generate a unified whole. Typically whole systems exhibit
behaviors and have properties that cannot be attributed to
an individual component. These system-level behaviors are
called emergent properties
[1
3]
. Understanding how the
different components and interactions drive the manifes-
tation of emergent properties is one major goal of systems
biology. Systems biology as a field is focused on the
understanding of multicomponent functional units. It has
begun to have enormous impact across biological sciences,
including ecology, population biology, evolutionary
biology as well as biochemistry, molecular and cell
biology, physiology, development and genetics. Here we
focus on systems biology at a cellular level.
e
CELLULAR SIGNALING: PATHWAYS
TO NETWORKS
Intrinsic to cellular processes is the receipt and processing
of information. The ability of a mammalian cell to live
