Chapter !11 - Systems Biology Code : KSI0020

<Index of Chapter 11>

 

Introduction to systems biology

The goal of systems biology is the synthesis of all biological data into a unified picture of the structure, dynamics, logistics and ultimately the logic of living things. 

System biology focuses on the integration of gene, RNA, and protein activity

Cells contain both physical and logical networks. Many interactions are common to both.

-Two parallel networks : physical and logical

-Statics and dynamics of networks

Cell- cell communication in microorgansisms : quorum sensing 

Static structure stability. 

Stability is an important goal of regulatory dynamics. 

Sources of metabolic stability include 

1. Constant rate of input

2. Feedback inhibition of enzymes

3. allosteric control of activity of enzymes

4. turning proteins on and off  by phosphorylation and dephosphrylation 

5. control of amounts of proteins by regulation of expression 

> Robustness is another crucial feature of the dynamics of biological networks. 

 

Pictures of networks as graphs

Graphs are abstract representations of networks. They show the connectivity of the network. labelled graphs can show physical distanes between nodes, or other properties of edges such as throughput capacity. 

Connevtivity / path / cycle 

A vitamin is a compound that we must eat because we can't synthesize it. Therefore, there can be no path in the metabolic network leading to a vitamin 

 

-Trees > Density of connections / fully connected /Power laws. 

 

Sources of ideas for systems biology

-Complexity of sequences

-Shannon's definition of entropy

-Randomness of sequences

-Static and dynamic complexity

-Computational complexity

 

The metabolome

-Classification and assignment of protein function

-Metabolic networks 

-Databases of metabolic pathways

-Methionine synthesis in Escherichia coli

-The kyoto Encyclopedia of genes and genomes (KEGG)

-Evolution and phylogeny of metabolic pathways

-Carbohydrate metabolism in archaea

-Reconstruction of metabolic networks

The enzyme commision (EC)  / Enzyme structures database 

An onthology is a formal set of well-defined terms with well-defined interrelationships that is a dictionary and rules of syntax. 

 

Regulatory networks

-Signal transduction and transcriptional control

-Structures of regulatory networks

Several databases assemble biochemical reactions into metabolic pathways. Individual seops are linked to enzyme commisiion and gene ontology consortium classfications of funtion. and to individual proteins that catalyse the reactions. These databases are useful in organizing the assignment of function to proteins identified in newly sequenced genomes 

 

Dynamics , stability , and robustness

-Robustness through redundancy

-Dynamic modelling

 

Protein interaction networks

-Structural biology of regulatory networks

Signal transduction and transcriptional control 

> General characteristics of all control pathways include the following 

1. A single signal can trigger a single response or many responses

2. A single response can be controlled bt a single signal or infulenced by many signals

3. Each responesse may be stimualatroy- decreaaseing an activity. 

4. Transmission of signals may damp out stimuli or amplify them. 

 

Protein-DNA interactions

-Structural themes in protein-DNA binding and sequence recognition

-An album of transcription regulators

 

DNA-protein complexes mediate several types of process

1. Replication, including repair and recombination

2. Transcription

3. Regulation of gene expression

4. DNA packaging, including nucleosomes and viral capsids.

 

Differnt processes requrie different degrees of DNA sequence specificity

 

<Specificities of DNA-binding proteins>

DNA binding proteins are relatively non-specific with respect to nucleotide sequence, including DNA replication enzymes and histones. 

Some recognize specific nucleotide sequences. 

Some DNA binding proteins recognize consensus sequences

Some recognize nucleotide seuqneces indirectly via modulations of local DNA structure 

 

Gene regulation 

-The transcriptional regulatory network of Escherichia coli

-Regulation of the lactose operon in E.Coli.

Operator / Promoter / Repressor / operon / cis-Regulatory rehion / transcription start site / Coonstituve mutant 

Common motifs in biological control networks. 

Regulatory networks are directed graphs. Some simple motifs, or common small subgraphs, from the lowest level of network struvture. Networks can reprogram themselves, within an orhanism and evolve between species. 

 

The genetic regulatory network od Saccharomyces cerevisiae

-Adaprability of the yeast regulatory network.