Prof. Garrett Odell
University of Washington
How and why are genetic networks robust?
Abstract: Mathematical models of how cross-regulatory genetic networks lay down gene expression patterns in the early fly embryo to prefigure its larval body plan show that such networks can be astonishingly robust to changes in the strengths and functional forms of the various interactions among genes and their products. This robustness is not merely theoretical; it exists in nature and for good reasons. George von Dassow, Ed Munro, Eli Meir and I made mathematical models based on mass action kinetics to predict temporal changes in the expression levels of RNAs and proteins in each of many cells in fruit fly embryos to find out whether experimentally proved interactions among genes and their products in the segment polarity network and the neurogenic network could account for the spatio-temporal gene expression patterns those networks actually make. Our mathematical models needed values for the 50-90 parameters that occurred in each model but none had been measured. We therefore used computers to search huge "boxes" in high-dimensional parameter space to get a glimpse of the set of points at which the model network exhibits the same behavior as the real network. The unexpectedly huge set of 'good' points we found corresponds to robustness of the network which would be astonishing were it not essential to make complex genetic modules functionally heritable. We are currently trying to understand how gene networks arose whose spatio-temporal pattern-formation repertoires seem mysteriously to be encoded in the topology of the network's conections, rather than in the strengths/functional forms of those connections. The origin of such robustness may be trivial if we recast the question appropriately. Regardless of how it arose, the kind of robustness we found mathematically has significant implications for medicine, for comparative developmental biology, and for cell biology.
Zeit: Freitag,
24. Juni, 2005, 16.15 (Kaffee/Tee um 15.30)
Ort: FU Berlin, Arnimallee 2-6, Raum 032 im EG