Center for Complex Biological Systems (UC Irvine)
Principal investigator: Arthur Lander, M.D., Ph.D, University of California, Irvine
Other key personnel: Anne L. Calof, Ph.D., Lee Bardwell, Ph.D., Qing Nie, Ph.D., Enrico Gratton, Ph.D., Frederic Y.M. Wan, Ph.D.
The UCI Center for Complex Biological Systems (CCBS) was founded in 2001 to promote research and education in Systems Biology. In 2007, CCBS became an NIGMS Center for Systems Biology, the only such center in the Southwestern U.S. Although activities in all areas of Systems Biology–including synthetic biology, genomics and functional genomics, computational biology, mathematical biology, biophysics, and bioengineering–are encouraged within the center, certain key areas and goals are emphasized. These include:
Spatial Dynamics: A central tenet of Systems Biology is that most biological processes are continuously varying in time, and cannot be understood apart from their dynamics. In fact, most biological processes are continuously varying in time and space–i.e., where things occur within cells, tissues or organisms is just as important as when they occur, and just as changeable over time. The behaviors of spatiotemporally dynamic systems are fundamentally more difficult to analyze than those of merely time-varying dynamic systems, which is why many Systems Biologists are attracted to systems that can (at least initially) be treated as space-invariant (i.e. “well-stirred”, as though the locations of things are not important). Yet many important phenomena in biology are so fundamentally spatial in nature, that ignoring space is simply impossible. These include phenomena like morphogenesis, pattern formation, chemotaxis, cell migration, cell polarity, tumor growth and metastasis, and many aspects of ecology. Even phenomena that are traditionally treated as well-stirred, such as gene expression, clearly have spatial aspects that have yet to be understood (e.g. influences of nuclear organization). CCBS is dedicated to the development and application of Systems Biology approaches for all such biological systems.
Mathematical and Computational Modeling: The study of spatial dynamics presents challenges for both mathematics and computation. The center conducts research and development on the mathematical analysis of high-dimensional systems; the rapid numerical solution of systems of partial differential equations; stochastic simulation; discrete models of cell behaviors in space and time; and the efficient exploration and representation of large parameter spaces.
Developmental Biology: Most of the major questions in Developmental Biology involve spatial dynamics: How are patterns formed robustly? How do tissues become organized? What controls growth and tissue homeostasis? CCBS leverages UC Irvine’s longstanding strength in experimental Developmental Biology to address questions of patterning, morphogenesis and growth control in organisms as diverse as flies, frogs, zebrafish, nematodes, mice and man.
Monitoring molecular events in live cells with fluorescence dynamics: To investigate the spatial dynamics of processes that are controlled at the molecular level, one needs spatiotemporal maps of molecular behavior. Processes such as diffusion, binding, reaction and catalysis need to be measured not only in homogenized samples, but in real time at specific locations within cells and tissues. CCBS works closely with the UCI Laboratory for Fluorescence Dynamics to develop and apply fluorescence fluctuation-based methods for extracting such information from biological samples. Among the methods used or in development are fluorescence correlation spectroscopy, photoactivation and photobleaching, image correlation spectroscopy, particle tracking, fluorescence lifetime imaging, “Number and Brightness” quantification of aggregation, pair-correlation microscopy, and digital holographic microscopy.
Training in Systems Biology: CCBS administers a Ph.D. training program in Mathematical, Computational and Systems Biology, that was developed with the assistance of a grant from the Howard Hughes Medical Institute to create new interdisciplinary Ph.D. programs. Currently, this program is supported by two NIH training grants. CCBS also organizes training activities for high school students, undergraduates, and postgraduate researchers, including workshops, journal clubs and symposia.