Cellular machinery is more complex than any technology humans have understood. Comprehending how this machinery self-assembles and works requires synthesizing interactions between molecular parts of cells into functional mechanistic models. Intelligent design of medical interventions requires this. The only tool capable of this synthesis is mathematical models solved on computers. Detailed case studies of particular cell biological phenomena, not abstract rhetoric, will sharpen this tool and prove its worth. The proposed Center of Excellence at Friday Harbor Laboratories will assemble a cross-disciplinary group of 14 scientists plus staff with this mission: to combine experiment and theory with computational modeling techniques the proposers have helped pioneer into detailed case studies of genetic networks operating in two different contexts-developmental pattern formation and cytoskeletal dynamics, and to promulgate this approach, and the tools supporting it. These studies will consolidate and extend the proposers' current efforts to comprehend: 1) how modules of cross-regulatory genes, installed identically in each cell in an embryo, form and stabilize spatio-temporal gene expression patterns causing cell determination; and 2) how biochemical and mechanical interactions among major cytoskeletal filament systems, molecular motors, cell adhesion proteins, and their myriad regulators cause cells to reorganize their internal components, move, change shape, and divide. Recruiting long-term salaried post-does and visiting sabbatical scientists to the Center and collaborating with them to make models of these phenomena, will teach them to wed computational modeling and experiments to comprehend biological complexity. Center outreach activities will include: 1) Perfecting and publishing computational methods for making and analyzing models of regulatory and cytoskeletal networks; 2) """"""""Hardening' and disseminating our software for building and analyzing gene network models, and for segmenting/visualizing 3D cytoskeletal structure from scanning confocal microscope data; 3) Teaching yearly research apprenticeship courses to recruit biology undergraduates early to careers combining theory, experiment and computation; 4) Hosting teaching workshops and round-table symposia to broadcast the Center's computational modeling successes, facilitate cross-breeding exchange with other scientists and recruit potential converts.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM066050-02
Application #
6612635
Study Section
Special Emphasis Panel (ZGM1-CMB-0 (CO))
Program Officer
Anderson, James J
Project Start
2002-08-01
Project End
2007-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$2,123,508
Indirect Cost
Name
University of Washington
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hashimoto, Hidehiko; Robin, Francois B; Sherrard, Kristin M et al. (2015) Sequential contraction and exchange of apical junctions drives zippering and neural tube closure in a simple chordate. Dev Cell 32:241-55
Zielke, Norman; Kim, Kerry J; Tran, Vuong et al. (2011) Control of Drosophila endocycles by E2F and CRL4(CDT2). Nature 480:123-7
Rafelski, Susanne M; Keller, Lani C; Alberts, Jonathan B et al. (2011) Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication. Phys Biol 8:026010
Dawes, Adriana T; Munro, Edwin M (2011) PAR-3 oligomerization may provide an actin-independent mechanism to maintain distinct par protein domains in the early Caenorhabditis elegans embryo. Biophys J 101:1412-22
Hoyos, Erika; Kim, Kerry; Milloz, Josselin et al. (2011) Quantitative variation in autocrine signaling and pathway crosstalk in the Caenorhabditis vulval network. Curr Biol 21:527-38
Sherrard, Kristin; Robin, François; Lemaire, Patrick et al. (2010) Sequential activation of apical and basolateral contractility drives ascidian endoderm invagination. Curr Biol 20:1499-510
Dawes, Adriana T (2009) A mathematical model of alpha-catenin dimerization at adherens junctions in polarized epithelial cells. J Theor Biol 257:480-8
von Dassow, George (2009) Concurrent cues for cytokinetic furrow induction in animal cells. Trends Cell Biol 19:165-73
Kim, Kerry J (2009) Ingeneue: a software tool to simulate and explore genetic regulatory networks. Methods Mol Biol 500:169-200
von Dassow, George; Verbrugghe, Koen J C; Miller, Ann L et al. (2009) Action at a distance during cytokinesis. J Cell Biol 187:831-45

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