Coordinator:

Holly Goodson (Dept. of Chemistry and Biochemistry, University of Notre Dame)

Participants:

M. Alber (Dept. of Applied and Computational Mathematics and Statistics, University of Notre Dame), B. Baker (Dept. of Chemistry and Biochemistry, University of Notre Dame), L. Barabasi (Dept. of Physics, University of Notre Dame), D. Chen (Dept. of Computer Science and Engineering, University of Notre Dame), C. D'Souza-Schorey (Dept. of Biological Sciences, University of Notre Dame), G. Forgacs (Dept. of Physics, University of Missouri, Columbia), J. Glazier (Dept. of Physics, University of Notre Dame), G. Hentschel (Dept.of Physics, Emory University), T. Hinchcliffe (Dept. of Biological Sciences, University of Notre Dame), J. Izaguirre (Dept. of Computer Science and Engineering, University of Notre Dame), P. Lee (Dept. of Immunology, Stanford University), A. Palmer (Dept. of Chemical Engineering, University of Notre Dame), J. Tang (Dept. of Physics, Indiana University, Bloomington), K. Vaughan (Dept. of Biological Sciences, University of Notre Dame)

Summary:

Subcellular organization underlies essentially all activities of eukaryotic life - polarized growth, cell motility, response to stimuli, and multicellular development. At first glance, the mechanistic origins of this organization seem so complex and diffuse as to be experimentally intractable. However, most aspects of eukaryotic cell organization depend on the cytoskeleton, the dynamic, interconnected array of filamentous polymers that extends over the entire interior of the cell. The cytoskeleton forms the active scaffold that segregates the chromosomes, allows the cell to move in response to stimuli, provides a dynamic highway network for intracellular transport, acts as an integral part of intracellular signal transduction networks, and helps determine and maintain cell polarity. Cell-level organization is an essential prerequisite to the organization of tissues and organisms during development. Thus, to understand the biocomplexity of development, we must understand in a quantitative and predictive way the properties of the cytoskeleton: how the dynamic interactions of the components form steady-state cytoskeletal structures, how other parts of the cell interact with the cytoskeleton, and how extracellular signals and interactions with the environment alter the behavior of the cytoskeleton, allowing complex behaviors such as chemotaxis, morphogenetic changes, and multicellular development. The specific goals we state below reflect the overall objective of the Center to understand the development of complex patterns and organization that arise in living systems at length scales from molecular to organismal.

Study of cytoskeletal components provides an ideal education for students of biocomplexity, allowing them to integrate modeling and experiment at all scales. Our understanding of both the actin and tubulin networks is mature enough that modeling is not only possible but necessary to understand the complex interactions between cytoskeletal proteins and the phenomena these interactions cause. Because we can mix clearly defined components with known interaction characteristics, either in test tubes or in silico, and compare the results, cytoskeletal components are ideal for developing and tuning quantitative and predictive mathematical models of biocomplexity.