Systems Biology (Methods in Molecular Biology)

(Tina Sui) #1

are transplantable and conserved in different organisms, for exam-
ple, functional module cell cycle are conserved in different organ-
isms, much of what we know about cell cycle can be traced back to
basic studies in yeast cells [29, 30], cell-specific functional modules
can be transplanted into different types of cells [31, 32], four stem
cell transcription factor induced cell type switch to iPS cell, includ-
ing morphology, proliferation, surface antigens, gene expression,
epigenetic status of pluripotent cell-specific genes, and telomerase
activity [31]. These evidences directly indicated that many
biological functions are relatively autonomous, the separated func-
tional modules can accomplish its own function and of course the
modules cross-talk with each other.
Another evidence is the theoretical modes based on functional
modules verifying their predictions match reality, such as cell cycle
[13, 33], apoptosis [34]. The quantitative model, by theoretical
predications and experimental validation, is the best way to test our
understanding of biological systems. The match of predications and
reality suggest that we can adopt the concepts of autonomous
functional modules. Therefore, we argue here that the biological
system is built by modules and cross-talk between modules, each
module can accomplish a relatively autonomous function, and
cross-talks between modules allow one function to influence
another and due to this we can model the functional modules
quantitatively. It also suggests that the recognition of functional
“modules” as a critical level of biological organization is important
for our understanding of biological systems.


2.Deeply hierarchy:there are regulators that serve as decision-
marking in modules to determine module’s fate, then the regula-
tors trigger the expression of a whole battery of downstream genes
related to the decided fate. Modules and cross-talk between mod-
ules can be simplified and specified by interactions of important
proteins, the general principles will allow us to grasp and manip-
ulate the modules.

Multiple experimental evidences suggest the existence of key
regulators, for example two regulatory proteins CI and Cro regu-
late phage lambda genetic switch [35], key regulators regulate
developmental process of sea urchin [36], four transcriptional fac-
tors induce human fibroblasts to pluripotent stem (iPS) cells
[31]. The module components include Genes (DNA), mRNA,
MicroRNA, Proteins, small molecules, etc. Among all the compo-
nents proteins play special roles in the biological system, because
they are the main biological function executor, they can regulate
gene expression, and they are key regulators in signaling transduc-
tion. It is clear that functions cannot be understood by studying the
single proteins [23, 37]. Important functions arise from the regu-
latory machinery. General modules and cross-talk between modules


Endogenous Molecular-Cellular Network Cancer Theory 219
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