Biology Reference
In-Depth Information
(A)
( substrates )
Environment ( metabolites )
( products )
E
i
E
i
E
i
(C)
(N)
(
)
(G)
Metabolic control
E
j
Metabolic
networks
(e.g. allosteric;
covalent)
E
i
E
k
E
x
E
n
E
i
E
j
E
z
E
y
(B)
Signal transduction
regulatory networks
( Catabolism -> ATP -> Anabolism )
[ Integration metabolic-
proteome studies ]
E
i
E
i
E
i
(F)
[ e.g.
Metabolic control
at the level of [E
i
]
( Multilevel control )
protein-protein,
protein-RNA
interactions ]
(DNA)
RNA
(E)
mRNA
(reg. RNAs)
Proteins
(epi)-genome
(C)
(D)
Transcriptional regulation
Translational regulation
FIGURE 18.2
Eukaryotic cell: hierarchy and levels of regulation. Schematic description of hierarchy, main regulatory levels and networks in the
eukaryotic cell, in direct interaction with the environment, subjected to distributed, multilevel control
[53,55,70]
(subcellular organelles other than the
nucleus are omitted for clarity). (A) Environment: the eukaryotic cell is not isolated, sensing fluctuations in external conditions (e.g., concentrations of
external compounds, pH, temperature) together with interactions with other organisms (e.g., via external signals; competition or cooperation). (B) Signal
transduction regulatory networks (e.g., protein
protein networks).
(C) Gene expression at the transcriptional level, resulting in a pool of mRNAs and regulatory RNAs ('transcriptome', balance of synthesis and degra-
dation). (D) Gene expression at the translational level, translational regulation. (E) Main pool of enzymes and regulatory proteins (i.e., 'proteome', balance
of synthesis and degradation), responsible for central regulatory and metabolic networks. (F) and (G) Intracellular enzymes and metabolites concen-
trations (balance of uptake, intracellular synthesis and conversion) mainly responsible for in vivo regulation of metabolic fluxes and metabolic networks
essential for balanced coupling between catabolism and anabolism. Abbreviations: [E
i
], pool of enzymes; (C) and (N), fluxes of assimilation of carbon and
nitrogen sources, respectively.
protein networks; DNA
protein, protein
RNA (ribonucleoprotein) and metabolite
e
e
e
e
their relation to cancer; cell polarity; control of pre-mRNA
splicing; eukaryotic translation initiation; evolution; aging
and extension of lifespan; protein folding and chaperone
networks, and as a model to gain insight into the molecular
pathology of neurodegenerative diseases (
[16]
and references
therein; see also below). All these advantages are positioning
S. cerevisiae at the forefront of the post-genomic era as
a touchstone model for eukaryotic systems biology studies
(see
[16,61]
and references therein). For an exhaustive
selection of examples of advanced post-genomic technolo-
gies and the latest discoveries in eukaryotic biology using S.
cerevisiae as a main reference model, at the (epi)-genome,
genome organization, transcriptional, proteome and metab-
olome levels, as well as DNA
we aim to show the main strategies to convert into reality the
huge potential of this reference model eukaryote for
comprehensive studies of the dynamics of (dys-)regulated
eukaryotic networks, with direct applications in biotech-
nology and human disease.
Data Analysis and Integration for Systems
Biology Studies: State-of-the-art Towards
Comprehensive Integration of 'Omics'
Datasets
Need for a Clear Definition of Objectives
and Experimental Design
A number of facts should be taken into account in all
comprehensive systems biology studies (from yeast to
human): (a) The need for a clear objective with clear-cut
protein, RNA
protein, pro-
e
e
tein
metabolome networks/interactions
and internal compartmentalization levels the reader can refer
to
[16,17]
and references therein. In the following sections,
protein, proteome
e
e
