This application requests continuation of funds for years 06-10 for the Resource on Population Kinetics (RFPK-also referred to as the Resource). RFPK's major goal is the development, application and dissemination of modeling methodology and software tools for biomedical uses in defining, understanding and managing health and disease. This goal is achieved by promoting the application of integrated systems modeling in biomedical research. This is done by providing consultation in model development and experimental design, by offering educational programs, and by developing new methods for incorporation in state-of-the-art software tools. Modern methods of scientific computing, in conjunction with inexpensive and powerful hardware, are driving a dynamic paradigm shift in how state-of-the-art scientific, engineering and business research are performed. RFPK is at the forefront of this shift in the biomedical community in its ability to communicate and collaborate with diverse disciplines in order to conduct its research. This multidisciplinary group is comprised of faculty, staff, students and collaborators in various fields of medicine, mathematics, statistics, software engineering, and the pharmaceutical industry. This research model unifies concept development, experimentation, simulation and implementation. Examples of this new approach in action are the human genome project, the design of the Boeing 777, and the design of financial derivatives. Factors driving this approach are the need to understand and manage complex dynamical systems, the need for accurate descriptions of physical phenomena, and the need for efficiency in the use of funds for research and development. The full impact of this paradigm shift has not reached the biomedical research community. The problem is rooted in the absence of software tools and educational programs targeted at the development of modeling skills for this community. A program that integrates both software development and education must be designed to answer this need. RFPK addresses this need directly in its specific aims, which are to: (1) develop new modeling methodologies for biological systems; (2) specify, design, develop, test, validate and maintain new software tools incorporating cutting-edge mathematics, statistics and computer science; (3) provide service to the research community through collaboration and consultation; (4) provide educational programs for the research community in systems modeling applications; and (5) disseminate RFPK technology and expertise via diverse educational programs that integrate medicine, statistics, computer science and bioengineering in a comprehensive problem-solving approach. Making these new tools and methods available to a broad audience is a complex problem that is best accomplished on a university campus. RFPK has assembled a multidisciplinary team consisting of scientific experts in model development and testing who collaborate with mathematicians, statisticians, and software engineers. RFPK involves four major universities, all of which contribute unique expertise to the individual projects. Its Administrative Core is located at the University of Washington.