Systems Biology Approach to Metabolic Syndrome

understanding BIOLOGY MEDICINE sis the po hy del mo data behavior interpretation COMPUTER AND NANOTECHNOLOGY SYSTEMS SCIENCE Ideas for a Systems Biology Approach to Metabolic Syndrome Joseph F. Koonce Department of Biology Case Western Reserve University Center of Excellence in Systems Biology 1 Overview of Presentation Center for Excellence in Systems Biology some relevant systems concepts  Apply systems concepts to metabolic syndrome  Explore a possible systems biology framework  Review 2 Ideas From Systems Theory Center for Excellence in Systems Biology  What is a system? System is an entity with bounded autonomy Complex system is a system of systems  Properties of complex systems Multi-levelness Emergent behavior 3 Questions About Multi-levelness Center for Excellence in Systems Biology levels arbitrary?  Do levels occupy domains of scale?  How are systems and subsystems coordinated?  How does system architecture (levels and connections) influence emergent behavior?  How does multi-levelness evolve? 4  Are Application to Metabolic Syndrome Center for Excellence in Systems Biology  System structure  Levels of organization  Coordination mechanisms  Emergent properties  Robustness  Predictability  Observability  Measurements  Experimental possibilities 5 Metabolic Syndrome Center for Excellence in Systems Biology Diabetes Dyslipidemia Heart Disease Obesity Diet Activity Genetics 6 Levels of Organization Center for Excellence in Systems Biology Organism Organ System Tissue Cell 7 Levels of Organization Center for Excellence in Systems Biology Organism Organ System Tissue Cell Digestive Circulatory Respiratory Immune and Lymphatic Excretory Endocrine Reproductive Nervous Integrumentary Skeletal Muscular 8 Levels of Organization Center for Excellence in Systems Biology Organism Organ System Tissue Cell Epithelial Connective Nervous Muscle 9 Levels of Organization Center for Excellence in Systems Biology Organism Organ System Tissue Cell 10 Possible Systems Framework for Metabolic Syndrome Center for Excellence in Systems Biology approach  Three levels of subsystems  Behavioral control mechanisms of subsystems  Coordination mechanisms between levels  Emergent behavior and manifestation of disease 11  Evolutionary/development Biological Multi-levelness Center for Excellence in Systems Biology Organism Cell All share the existence of a fundamental biological behavior guidance system that allocates energy between reproductive and non-reproductive investments through cycles of reproduction. Genome/Proteome 12 Evolution of Mulit-levelness Center for Excellence in Systems Biology  Essential ingredients Subsystems exist in a system having limited resources and rules of interaction Mutation Natural selection based on maximum use of available free energy 13 Evolution of Mulit-levelness Center for Excellence in Systems Biology  Conditions for emergence of multilevelness  A mechanism for coalescence of subsystems to form aggregate subsystems that have unified behavior  Unified subsystems interact in their characteristic domain of scale, which thus forms a level  A mechanism to coordinate behavior of subsystems 14 Consequences of Evolutionary Framework Center for Excellence in Systems Biology Identifying domains of scale depends upon knowing size of subsystems  Understanding signal transmission and responsiveness are key to understanding linkage of subsystems  Understanding coordination of subsystems requires understanding how signal reception alters behavioral guidance mechanism  15 Application to Metabolic Syndrome Center for Excellence in Systems Biology Sick Adult Adult Juvenile Cells in various tissues alter phenotypes in ways that emerge as a disease condition. Environment: Embryo •Diet •Activity Zygote Genetics 16 Questions Arising From Framework Center for Excellence in Systems Biology How variable are cell phenotypes (in tissues) from genotypes?  How do signaling cascades change during development and aging?  Are there critical control mechanisms that alter cell and organism behavior?  Are there a key sets of signal systems that operate on allocation at the level of cell growth and development?  17 Elements of a Research Approach Center for Excellence in Systems Biology  Conceptual studies Search for organizing principles Identification of categories of systems  Theoretical studies Modeling (e.g. DEVS applications) Multi-level coordination and cross-talk  Experimental studies—hypothesis driven 18