Speaker: Prof. Sima Setayeshgar
From: Department of Physics, Indiana University, Bloomington
Date/Room/Time: Tuesday, April 12, 2005 / 127 Nieuwland Science/ 4-5 PM

Tea begins at 3:30 PM in Room 257 of Hurley Hall

Title: Physical Limits to Biochemical Signaling

Abstract:
Many biochemical processes in living cells that regulate the cell's functions are inherently stochastic, as the relevant molecules are present in small copy numbers making their fluctuations significant. Twenty-five years ago, Berg and Purcell showed that bacterial chemotaxis, where a single celled organism must respond to small changes in concentration of chemicals outside the cell, is limited directly by molecule counting noise, and that aspects of the bacteria's behavioral and computational strategies must be chosen to minimize the effects of this noise. The chemotaxis paradigm can be generalized to other biochemical mechanisms governing important functions of the cell, from translating external signals to appropriate internal signaling molecules, replicating DNA, reading genes and driving metabolism to triggering cell death. How reliably can these tasks be carried out in the presence of inherent fluctuations in the numbers of the key players? Specifically, how accurately can a biological sensor, which in turn controls downstream biochemical events, measure the concentration of an internal or external signaling molecule? We revisit and generalize the classic results of Berg and Purcell from a statistical mechanics point of view. Given improved experimental methods allowing accurate measurements, it is now possible to compare the actual performance of biochemical signaling systems within the cell with the corresponding counting noise limits. We compare this limit with the physical performance of several examples for which experimental data is available, an important one being the binding of transcription factors to genes. An emerging theme that can be made increasingly quantitative is that for its crucial tasks, the performance of the cell really does approach the limits set by basic physical laws.

This work is in collaboration with Prof. William Bialek, Department of Physics and Lewis-Sigler Institute, Princeton University.