Biology Reference
In-Depth Information
Chapter 19
Systems Biology of Caenorhabditis elegans
Andrew Fraser
1
and Ben Lehner
2
1
The Donnelly Centre, University of Toronto, 160 College Street, Ontario M5S 3E1, Canada,
2
European Molecular Biology Laboratory (EMBL)-Centre
for Genomic Regulation (CRG) Systems Biology Unit and Institucio´ Catalana de Recerca i Estudis Avan¸ats (ICREA), CRG, Universitat Pompeu Fabra
(UPF), c / Dr Aiguader, 88, Barcelona 08003, Spain
Chapter Outline
Introduction: The System before the Sequence
367
Single Cell-Resolution Analysis of Gene Expression
377
Forward and Reverse Genetics in the Worm: How 97mb
says 'Make a Worm'
Global Maps of Transcription Factor-Binding Sites and
Chromatin Organization
369
378
From 'How Does This Work?' to 'What Does This Do?'
369
Variation in Gene Expression among Individuals and its
Phenotypic Consequences
Classical Screens: Finding the Core Modules that
Control Worm Development
379
370
Proteomics in C. elegans: Global Maps of Protein
Expression and Protein
Classical Screens with Next-Generation Sequencing
Protein Interactions
380
e
e
Genetics Leaps Forward
371
Integrative and Dynamic Modeling to Link Genotype to
Phenotype
Persuading Worms to take Enough Drugs
e
Chemical
380
Genomics in the Worm
372
Data Integration and Genome-Scale Networks to
Connect Genes and Modules to Phenotypic Variation
Reverse Genetics and the Magic of RNAi
373
380
Expressing and Regulating an Animal Genome
376
Dynamic Models of Developmental Processes
382
Genome-Wide Maps of Normal and Perturbed Gene
Expression
Outlook
382
377
References
384
INTRODUCTION: THE SYSTEM BEFORE
THE SEQUENCE
When it comes to systems biology, Caenorhabditis elegans
is unique amongst the current major model organisms.
Unlike in the fly, the yeasts, or the mouse, systems biology
has not emerged as a later development of classical genetics
studies but has been at the heart of the worm community
philosophy from the very start. The goal of completeness
(later refined to CAP
processors such as the lac operon. In this sense, the first
key steps in the establishment of the worm have a funda-
mentally different flavor from those of the fly. Fly
research, in its earliest days, was by necessity top-down.
T.H. Morgan's fly room was established in the first decade
of the 20th century at a time when almost all the basic
principles of genetics were unknown. Although the
Boveri
Sutton chromosome theory had proposed as early
as 1903 that chromosomes were the fundamental carriers
of heritable genetic material
[1,2]
, the first two decades of
the 20th century were awash with conflicting theories as to
how evolution and inheritance operated. By 1915,
however, the publication of The Mechanism of Mendelian
Heredity by Morgan et al.
[3]
was a huge advance in
genetics and provided a single accessible synthesis of the
major concepts of, among others, Mendel, de Vries,
Boveri, and Sutton, and shaped the next phase of genetics
research. Thus the 'top-down' nature of early fly research
(starting with phenotypic outcome and attempting to
unravel the mechanistic basis) was born out of necessity
e
Complete, Accurate, and Perma-
nent) was central in Sydney Brenner's initial proposal to the
MRC
e
indeed, his vision of 'taming' the worm culminates
with the modest idea that 'We intend to identify every cell
in the worm and trace lineages'. The audacity of this idea of
completeness, in effect the intellectual 'taming' of
a complex biological system, set the tone of early worm
research and it is an approach that persists.
The worm is the intellectual descendant of phage
research and of the glimpses of the logic of genetic control
seen through detailed analyses of prokaryotic information
e
