GENE NETWORKS: FROM MOLECULES TO MECHANISTIC MODELS

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

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, as does the intelligent design of medical interventions. 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 it'sworth. The proposed center 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 we have helped pioneer into detailed case studies of genetic networks operating in two different contexts, and to promulgate this approach, and the tools supporting it. The two contexts extend the proposers' current research: 1 .developmental pattern formation (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.cytoskeletal dynamics (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-docs and visiting sabbatical scientists to the center and collaborating with them to make models of these, or other systems they study, will teach them to make and use computational models to comprehend biological complexity. Other outreach activities: 1) Perfecting and publishing computational methods for making and analyzing models of regulatory and cytoskeletal networks; 2) "Hardening" and disseminating our softwarefor 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