Regulatory networks in cells exhibit important dynamical behaviors, such as bistability (e.g. epigenetic switch) and oscillation (e.g. clocks, cell cycle). Ultrasensitive or `all-or-none-F¢ gene expression is a necessary feature for the emergence of such dynamics in gene networks. In biology, many regulatory molecules are sequestered by an inhibitor into an inactive complex. Using an experimental approach in budding yeast, I will demonstrate how protein sequestration generates tunable, all-or-none thresholds in gene expression. A simple quantitative model for this genetic network shows that both the threshold and the degree of ultrasensitivity depend upon the abundance of the inhibitor, exactly as observed experimentally. The abundance of the inhibitor can be altered by simple mutation; thus ultrasensitive responses mediated by protein sequestration are easily tunable. Gene duplication of regulatory homodimers and loss-of-function mutations can create dominant-negatives that sequester the original duplicate into an inactive complex. These results suggest a mechanism for the rapid evolution of bistable switches and oscillators in regulatory networks.-b
Coffee and cookies before the presentation at 3:15 pm, and refreshments after the presentation will both be served in Room 128.