Physiological System Dynamics Laboratory, University of Michigan. The Physiological Systems Dynamics Laboratory, led by Daniel Beard and Brian Carlson, studies the dynamics of physiological systems in health and disease. We use a combination of experiments and analysis with multi-scale computational models to study the function of the cardiovascular system: how the mechanics of the circulatory and respiratory systems are governed by neural and humoral mechanisms. Multi-scale models provide the means to simulate the integrated operation of metabolic pathways (e.g., oxidative ATP synthesis in the heart), cellular functions (e.g., cellular calcium handling and actin/myosin cross-bridge dynamics), whole-organ function (e.g., mechanics of cardiac pumping), and whole-body body cardiopulmonary function. Experiments are used to identify and validate models representing individual components: in vitro experiments using purified enzymes, purified mitochondria, isolated cells, etc., and in vivo experiments to observe how all these pieces work together. Models that integrate function across these multiple systems and scales are used to identify novel hypotheses for the molecular mechanisms of diseases, identify molecular targets to effect desired outcomes, and to help translate findings from animal models to the clinic.
ABI Physiome Group. The Auckland Bioengineering Institute is a world leader in the pursuit of the Virtual Physiological Human and IUPS Physiome Project. Within the ABI, the Physiome Group is leads the development of data formats and the implementation of software support that provides the foundation for the exchange of complex multiscale and multi-physics mathematical models of physiological systems. The ABI Physiome Group collaborates with worldwide partners to ensure interoperability and data exchange is possible across a wide spectrum of mathematical modelling in biology, notably as active participants and leaders in the Computational Modeling in Biology Network (COMBINE). The ABI Physiome Group also provides support for the Physiome Model Repository and leads the development of the software which powers that repository.
Cardiac Mechanics Research Group, University of California San Diego. The Cardiac Mechanics Research Group uses experimental and computational models to investigate the relationships between the structure of cardiac muscle and the electrical and mechanical function of the heart during ventricular remodeling, repair and arrhythmia. The PIs are Drs. Andrew McCulloch and Jeff Omens. In vivo, genetically engineered mouse models are used for studies of the roles of cytoskeletal, sarcomeric, intercalated disk, membrane associated and regulatory molecules in mechanotransduction and mechanoelectric feedback, ventricular hypertrophy and cardiomyopathy, post-myocardial infarction remodeling and regeneration, and arrhythmia mechanisms. In vitro, tissue engineering of the cell microenvironment using bionanoprinting, microlithography and microfluidics are used to investigate the role of cell-cell and cell-matrix interactions in cardiac mechanical signaling, mechanoelectric feedback and the pathogenesis of heart failure. The systems biology of cardiac hypoxia responses are being studied in Drosophila and mice, and the networks that confer hypoxia tolerance and susceptibility are under investigation. Multi-scale computational modeling together with in-vitro experimental studies are used to investigate excitation-contraction coupling and contractile mechanisms and their regulation and the role of mechanoelectric feedback in action potential propagation. Patient-specific modeling based on non-invasive medical imaging and in-vivo clinical measurements is being used to explore atrial fibrillation and cardiac resynchronization therapy for heart failure, in collaboration with Dr. Sanjiv Narayan at Stanford and David Krummen at the San Diego VA Medical Center.
Cardiovascular Dynamics Group. The Cardiovascular Dynamics Group is composed of professors, postdoctoral research associates, graduate students, and undergraduate students in the Department of Mathematics and the Biomathematics Department at North Carolina State University. We are interested in various models and parameter estimation of physiological phenomena.
The Semantics of Biological Processes Group, University of Washington. The Semantics of Biological Processes group carries out research in the representation and use of process knowledge for biomedical applications. As a specific example, we have developed methodology and tools for providing semantics to biosimulatoin models of physiology and pathology. These semantics aid researchers in searching for, understanding, and re-using biosimulation models that others have created. This work leverages resources such as the CellML model repository and the Biomodels database of models. Our main product is the SemGen tool, which facilitates searching, extraction and merging models. For more information, see our web pages.
The Physiome Project at the University of Washington. The University of Washington contributions to the Virtual Physiological Rat-to-Human project are in management, technology, and science. The management is as a participation in overviewing the science, guiding the overall direction, and aiding in defining and achieving the longterm goals.
Technology support includes:
- Maintaining the Physiome Model Repository for archiving and dissemination of the models and methods of analysis produced by VPR for use by the scientific community at large. Models are available in Matlab and as JSim project files, the latter being run either over the web on the UW server or downloadable for all platforms. VPR-originated models are distinguished.
- Developing the technologies for automated model construction from archived modules. Two methods are available, using SemSim / SemGen for defining and annotating modules and combining them, or using MPC (Mathematical Program Constructor) to construct multicomponent, mono or multi-scale models from annotated modular components, each of which is itself an operational model.
- Develop systems for reproducible science, including data storage, analysis using quantitatively testable hypotheses, modeling analysis and automated optimization, confidence limit evaluation and uncertainty quantification, and ending up with REPs (Reproducible Exchange Packets) for open source distribution that contain data, models, and the computational setup for the analysis.
- Because large complex models require operations manuals and training, tutorials are developed to take investigators through sequences of models and operations in selected target topics such as vascular mechanics, transmembrane transport, respiratory gas exchange, intermediary metabolism.
- Providing courses for investigators wishing to develop their modeling capabilities, and to develop collaborative projects directly or indirectly related to physiological and pharmacologic modeling and integrative systems analysis. These are usually 1-week courses for graduate students, postdocs and faculty participants.
The science projects center on transport in biological systems, from flows and flow distributions in organs, to transmembrane transport, signaling, and intercellular communication, biochemical systems and to integrative system modeling. Examples are fatty acid transport systems, nucleoside multicellular transport and metabolism in convection diffusion systems, and cardiac electrophysiology.
The Kamp Lab at the University of Wisconsin
