Bulletin of the American Physical Society
2009 APS March Meeting
Volume 54, Number 1
Monday–Friday, March 16–20, 2009; Pittsburgh, Pennsylvania
Session A7: Systems Biology of Natural and Synthetic Circuits |
Hide Abstracts |
Sponsoring Units: DBP Chair: Jan Skotheim, Standford University Room: 407 |
Monday, March 16, 2009 8:00AM - 8:36AM |
A7.00001: Feedback and Modularity in Cell Cycle Control Invited Speaker: Underlying the wonderful diversity of natural forms is the ability of an organism to grow into its appropriate shape. Regulation ensures that cells grow, divide and differentiate so that the organism and its constitutive parts are properly proportioned and of suitable size. Although the size-control mechanism active in an individual cell is of fundamental importance to this process, it is difficult to isolate and study in complex multi-cellular systems and remains poorly understood. This motivates our use of the budding yeast model organism, whose Start checkpoint integrates multiple internal (e.g. cell size) and external signals into an irreversible decision to enter the cell cycle. We have endeavored to address the following two questions: What makes the Start transition irreversible? How does a cell compute its own size? I will report on the progress we have made. Our work is part of an emerging framework for understanding biological control circuits, which will allow us to discern the function of natural systems and aid us in engineering synthetic systems. [Preview Abstract] |
Monday, March 16, 2009 8:36AM - 9:12AM |
A7.00002: to be determined by you Invited Speaker: |
Monday, March 16, 2009 9:12AM - 9:48AM |
A7.00003: Signal integration, gain, and integral feedback in the \textit{Escherichia coli} chemotaxis network Invited Speaker: Bacteria are able to sense chemicals in their environment, allowing cells to swim towards nutrients (attractant chemicals) and away from repellents (toxic chemicals). The chemotaxis network of the model bacterium \textit{Escherichia coli} possesses remarkable signaling properties including high sensitivity to small changes in chemical concentration over a wide range of ambient concentrations. These signaling properties rely on the architecture of the circuit, including elements that implement signal integration, gain, and integral feedback. All of these elements rely on receptor clustering, which occurs at multiple length scales. At a small scale, the chemotaxis receptors form stable homodimers which then assemble into larger complexes in which receptors of different chemical specificities are intermixed, with trimers of dimers believed to be the smallest signaling unit. At a larger scale, $\sim $10,000 receptors form large polar and lateral receptor clusters. I will discuss recent experimental and theoretical progress in understanding how the biophysics of chemotaxis receptors leads to the remarkable signaling properties of the chemotaxis network. [Preview Abstract] |
Monday, March 16, 2009 9:48AM - 10:24AM |
A7.00004: Dissecting the nitrogen assimilation system of E. coli: from molecules to physiology Invited Speaker: Nitrogen assimilation is a major branch of cellular metabolism. For enteric bacteria such as E. coli, all of the nitrogen groups needed in biosynthesis are converted from ammonia by a relatively simple system comprised of 3 enzymes and 3 intermediate metabolites. This system is intricately regulated, at both the transcriptional and post-translational levels according to the nitrogen and carbon/energy status of the cell. While specific pieces of this regulation have been known for a long time, the strategy of regulation relating nitrogen influx to cellular demand is poorly understood. Clearly, the paradigm of end-product feedback inhibition well-established for the regulation of individual metabolic pathways is inadequate since there are too many products involving nitrogen. Through extensive experimental studies including quantitative characterization of the levels of key metabolites and enzymes for a carefully chosen spectrum of growth conditions and mutants, we obtain a dynamic picture of how the cell matches its rate of nitrogen assimilation with physiological needs through the intermediate metabolites. [Preview Abstract] |
Monday, March 16, 2009 10:24AM - 11:00AM |
A7.00005: Building a genetic transistor in yeast: How protein sequestration generates a tunable ultrasensitive or all-or-none response Invited Speaker: Protein sequestration, where an active protein (A) is bound in an inactive complex by an inhibitor, is a common molecular mechanism in natural regulatory circuits. The inhibitor serves as a molecular sink that can buffer and titrate low concentrations of A. If sufficient protein A is produced, then the sink is saturated and A will exhibit an ultrasensitive or all-or-none response. Theory demonstrates that this ultrasensitivity grows both as a function of inhibitor concentration and increased binding affinity. Although protein sequestration can theoretically generate tunable ultrasensitive responses, this regulatory principle has never been tested experimentally. We used a synthetic genetic circuit in budding yeast to show that sequestration of a basic leucine zipper transcription factor (C/EBPa) by a dominant-negative inhibitor converts a graded transcriptional response into an ultrasensitive response, with apparent Hill coefficients up to 12. We developed a simple quantitative model for this genetic network that demonstrates how the threshold and degree of ultrasensitivity depend upon the abundance of the inhibitor, exactly as observed in our experimental results. Many proteins in natural regulatory networks involve the formation of inactive protein-protein complexes, e.g. stoichiometric inhibitors of kinases and dominant-negative inhibitors of transcription factors. Our results demonstrate that protein sequestration can provide potent and tunable ultrasensitivity in genetic networks. Ultrasensitive or all-or-none responses are critical for robust bistable or oscillatory genetic networks, and our findings suggest that protein sequestration might play an unappreciated role in facilitating the evolution of bistable or oscillatory circuits in natural systems. [Preview Abstract] |
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2024 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
100 Motor Pkwy, Suite 110, Hauppauge, NY 11788
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700