M&SNet Joint Projects

Multiscale M&S of Biological Systems

By

Bernard P. Zeigler, C. Anthony Hunt & Tuncer I. Ören

An ambitious project involving the methodology of modeling and simulation for biological and other complex systems has been proposed to the National Science Foundation. This multi-national, multi-disciplinary, multi-investigator proposal is the first to come out of the newly organized McLeod Modeling and Simulation Network, known as M&SNet. This is a consortium of co-operating independent organizations that provides a framework — under the SCS umbrella — for M&S research groups to interact, share expertise, and work on problems of common interest.

Led by Dr. C. Anthony Hunt of the BioSystems Group at the University of California, San Francisco, the proposed research team is built on a core from M&SNet member institutions .These include the Arizona Center for Integrative Modeling and Simulation (ACIMS), the Ottawa Center of the MISS (OC-MISS), the Auburn Modeling and Simulation Laboratory (AMSL) and Virginia Modeling, Analysis and Simulation Center (VMASC).

Computational limitations in the past encouraged building a hodge-podge of models from different perspectives, at different scales, and at different levels of resolution. Today, given that computational power is no longer as constraining as it used to be, the project goal is to advance the state of theory, science, and engineering of complex systems to allow both developing partial models for different aspects of a system and integrating them into a larger framework that can provide a more complete and unified picture of the system as a whole.

To provide the context for accomplishing these goals, the team will build models of three different experimental biological systems:

how normal and diseased rat liver removes and metabolizes non-native compounds such as drugs from blood that passes through it,
the process and events in genetically engineered mice by which some white blood cells first attach to blood vessel walls and then move into the adjacent tissue in response to an infection or inflammation, and
how a single isolated human cell grows and develops, in the laboratory, into a recognizable, specialized tissue structure.

These quite different and challenging processes – liver filtration, immune response, and cell morphogenesis – have been selected to help insure that the newly developed theory, methods, and modular components are as useful and usable in one simulated biological context as another.

The long-term project plan is to create and disseminate biological component models that can exhibit many different behaviors that are observable in laboratory experiments. Moreover, such models can be composed to test prevailing hypotheses about how biological functions, such as waste filtering by liver tissue, really work. Besides the educational implications for training a new generation of M&S-aware doctors, these “in silico biomimetic” systems will be used to rapidly test new drug compounds that are either too dangerous or too expensive to synthesize in actual pharmacological labs. This will ultimately lower the cost of new treatment options for a range of medical conditions and greatly increase the pace at which they can be certified for public consumption.

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