Bulletin of the American Physical Society
APS March Meeting 2010
Volume 55, Number 2
Monday–Friday, March 15–19, 2010; Portland, Oregon
Session W7: Biological Networks |
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Sponsoring Units: DBP GSNP Chair: Jin Wang, State University of New York, Stony Brook Room: Portland Ballroom 254 |
Thursday, March 18, 2010 11:15AM - 11:51AM |
W7.00001: Sources of non-linearity in the mitotic trigger Invited Speaker: Quantitative biochemical studies have shown that the Cdk1/APC system, which drives entry into and exit from mitosis, functions as a relaxation oscillator. The bistable switch for the oscillator is provided by the Cdk1/Wee1/Cdc25 sub-system, which consists of a pair of mirror-image positive feedback and double-negative feedback loops. In turn, the bistable switch relies on the ultrasensitive sigmoidal response functions of the two loops' components. Here we have investigated the mechanisms through which Wee1 and Cdc25 generate ultrasensitive responses. Our results argue that the ultrasensitivity arises mainly through cooperative multisite phosphorylation and competition. [Preview Abstract] |
Thursday, March 18, 2010 11:51AM - 12:27PM |
W7.00002: Landscape and Flux Framework for Networks Invited Speaker: We developed a global framework to robustness of networks applied to biological oscillation by directly exploring the probabilistic distribution in the whole protein concentration space (therefore global) for oscillations with a stochastic approach. We uncovered two distinct natures essential for characterizing the global probabilistic dynamics of biological oscillations: the underlying potential landscape directly (logarithmically) related to the steady state probability distribution and the corresponding flux related to the speed of the protein concentration changes. We found that the underlying potential landscape for the oscillation has a distinct closed ring valley shape when the fluctuations are small. This global landscape structure leads to attractions of the system to the ring valley. On the ring, we found that the non-equilibrium flux is the driving force for oscillations. Therefore, both structured landscape and flux are needed to guarantee a global robust oscillation. The barrier height separating the oscillation ring and other areas derived from the landscape topography, is shown to be correlated with the escaping time from the limit cycle attractor, and therefore provides a quantitative measure of the robustness for the network. The landscape becomes shallower and the closed ring valley shape structure becomes weaker (lower barrier height) with larger fluctuations. We observe that the period and the amplitude of the oscillations are more dispersed and oscillations become less coherent when the fluctuations increase. When the fluctuations become very large, the landscape is flattened out and coherence of the oscillations is destroyed. Robustness decreases. When the fluctuations are small, changing the inherent parameters of the system such as chemical rates, equilibrium constants and concentrations can lead to different robust behaviors such as multi-stability. By exploring the sensitivity of barrier height on the parameters of the system, we can identify critical kinetic parameters important for robust oscillations. This provides a basis for reengineering and design. [Preview Abstract] |
Thursday, March 18, 2010 12:27PM - 1:03PM |
W7.00003: Molecular noise, cellular behavior and navigation strategies Invited Speaker: Bacterial chemotaxis is a cellular navigation system that allows bacteria to move towards sources of attractants and to avoid repellants. Although the chemotaxis network consists of just a few molecular species, it can perform complex cellular functions such as adaptation in response to environmental changes. This pathway is also one of the best characterize signal transduction pathways in biology. I will analyze the effect of the intracellular localization of the molecular components of this model system on its adaptation dynamics and ultimately on the behavior of an individual bacterium. [Preview Abstract] |
Thursday, March 18, 2010 1:03PM - 1:39PM |
W7.00004: Spatially-Extended Cellular Signals - The Case of Chemotaxis Invited Speaker: Many models of cellular signal processing treat the cell as a well-mixed chemical reactor in which spatial concentration gradients can be ignored. Often, however, this is a poor assumption and one must come to grips with spatially-extended (nonlinear and often stochastic) dynamical processes to understand cell response. In this talk, we will focus on the directed motility (aka chemotaxis) of eukaryotic cells, where the cellular decision regarding which way to go must of necessity involve creating a non-trivial internal pattern of downstream effectors and hence must involve intracellular spatial degrees of freedom. We will compare several models of this type to recent experiments using Dictyostelium as a model organism. [Preview Abstract] |
Thursday, March 18, 2010 1:39PM - 2:15PM |
W7.00005: Beyond Optimality to Understanding Neuronal Circuits Invited Speaker: I will summarize recent theoretical and experimental work that shows that similar circuit outputs can be produced with highly variable circuit parameters. This work argues that the nervous system of each healthy individual has found a set of different solutions that give ``good enough'' circuit performance. I will use examples from theoretical and experimental studies using the crustacean stomatogastric nervous system to argue that synaptic and intrinsic currents can vary far more than the output of the circuit in which they are found. These data have significant implications for the mechanisms that maintain stable function over the animal's lifetime, and for the kinds of changes that allow the nervous system to recover function after injury. In this kind of complex system, merely collecting mean data from many individuals can lead to significant errors, and it becomes important to measure as many individual network parameters in each individual as possible. This work raises the question of the extent to which neuromodulation can be constant with underlying circuit parameter variation. To address this question, we construct two cell reciprocally inhibitory circuits using the dynamic clamp from biological GM neurons of the crab stomatogastric ganglion. We then describe the output of the circuits while sweeping through a range of synaptic and intrinsic conductances, first in control saline and then in the presence of serotonin. We find that serotonin extends the ranges of parameters that produce alternating bursting. Moreover, although serotonin's effects are highly robust and significant on the entire population, individual networks respond anomalously. These data demonstrate that while neuromodulation may have robust actions on a population, not all individuals may respond as do the majority. These findings have important implications for evolution. [Preview Abstract] |
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