System Biology Study Group Walker Research Group Spring 2007

Definition: System Biology The process of network of genome- scale network reconstruction, followed by the synthesis if in silico models describing their functionalities, is the essence of system biology.

Key concepts Enumeration of biological components; and Enumeration of biological components; and Identification of the links that connect processes Identification of the links that connect processes

What is a system? “...parts in interaction.” Von Bertalanffy General System Theory 1968

What is a system? A system is an assemblage or combination of elements or parts forming a complex or unitary whole, such as a river system or a transportation system…” “A system is an assemblage or combination of elements or parts forming a complex or unitary whole, such as a river system or a transportation system…” Blanchard and Farbrycky System Engineering and Analysis 1998

Classification of Genetic Circuits Genetic Circuit Biological Databases. Gene sequences. Genes. Gene function. Gene family GeneTransfer Evolutionarydynamics Information Cell fate processes Energy Metabolism Transport Metabolic Engineering Cell division Cell motion Cell differentiation Tissue Engineering Translation Posttranslationmodifications Transcription Source: Palsoson, B System Biology

Some characteristics of genetic circuits They are complex They are complex They are autonomous They are autonomous They are robust They are robust They function to execute a physicochemical process They function to execute a physicochemical process They have “creative functions” They have “creative functions” They are conserved, but can be adjusted They are conserved, but can be adjusted Bioinformatics Bioinformatics Control theory Control theory System science System science Transport and kinetic theory Transport and kinetic theory Bifurcation analysis Bifurcation analysis Evolutionary dynamics Evolutionary dynamics Characteristics Analysis Method Source: Palsoson, B System Biology

Four Principal Steps Gen- Transcript- Proteo-Metabol- Reconstruction of biochemical reaction network Topology Noise Constraints Senstivity Dynamics Phenotypic space “practically infinite” for most organisms Source: Palsoson, B System Biology 1.Component Plurality of – omics 2.Reconstruction “systematic annotation” one set of reactions arising from the genome 3.In silico modeling plurality of methods 4.Hypothesis generation and testing.

Systematic Annotation Source: Palsoson, B System Biology

Input-output Modeling of Poultry Waste Management System

System of Linear Equations (24) (25) (26) (27) (28) (29)

Continuity Constraints: (14) (15) (16) (17) (18) (19)

System of Linear Equations for Poultry Waste Problem (35)

Roots of System Biology Source: Palsoson, B System Biology

Component View Source: Palsoson, B System Biology

Links Links between molecular components are basically given by chemical reactions or associations between chemical components: Covalent bonds Association of molecules

Chemical Transformation Properties Stoichiometry – the stoichiometry of chemical reactions is fixed and is described by integral numbers counting molecules that react and that form Stoichiometry – the stoichiometry of chemical reactions is fixed and is described by integral numbers counting molecules that react and that form Relative rates – all reactions inside a cell are governed by thermodynamics. Relative rates – all reactions inside a cell are governed by thermodynamics. Absolute rates – the absolute rates of chemical reactions inside cells are highly manipulable. Absolute rates – the absolute rates of chemical reactions inside cells are highly manipulable.

Functional States The functional states of biological reactions networks are constrained by the physicochemical nature of the intracellular environment. The functional states of biological reactions networks are constrained by the physicochemical nature of the intracellular environment. There is a highly developed spatiotemporal organization that orients the biological components and determines the transient nature of the interactions. There is a highly developed spatiotemporal organization that orients the biological components and determines the transient nature of the interactions.

Theory-Based vs Constrain Based Analysis Source: Palsoson, B System Biology

Constraining Allowable Functional States A network can fundamentally have many different states or many different solutions. Network have many different dehaviors that are picked based on evolutionary history. Networks can carry out the same function in many different and equivalent ways.

Hierarchical organization Source: Palsoson, B System Biology Microbial Communities?