Bulletin of the American Physical Society
APS March Meeting 2010
Volume 55, Number 2
Monday–Friday, March 15–19, 2010; Portland, Oregon
Session T13: Focus Session: Stochastic Processes in Biology II |
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Sponsoring Units: GSNP DBP Chair: L. Shaw, College of William and Mary Room: B112 |
Wednesday, March 17, 2010 2:30PM - 2:42PM |
T13.00001: Listening to the Noise: Random Fluctuations Reveal Gene Network Parameters Brian Munsky, Brooke Trinh, Mustafa Khammash The cellular environment is abuzz with noise originating from the inherent random motion of reacting molecules in the living cell. In this noisy environment, clonal cell populations exhibit cell-to-cell variability that can manifest significant prototypical differences. Noise induced stochastic fluctuations in cellular constituents can be measured and their statistics quantified using flow cytometry, single molecule fluorescence {\em in situ} hybridization, time lapse fluorescence microscopy and other single cell and single molecule measurement techniques. We show that these random fluctuations carry within them valuable information about the underlying genetic network. Far from being a nuisance, the ever-present cellular noise acts as a rich source of excitation that, when processed through a gene network, carries its distinctive fingerprint that encodes a wealth of information about that network. We demonstrate that in some cases the analysis of these random fluctuations enables the full identification of network parameters, including those that may otherwise be difficult to measure. We use theoretical investigations to establish experimental guidelines for the identification of gene regulatory networks, and we apply these guideline to experimentally identify predictive models for different regulatory mechanisms in bacteria and yeast. [Preview Abstract] |
Wednesday, March 17, 2010 2:42PM - 2:54PM |
T13.00002: Noise Reductions in Coupled Genetic Oscillatory Systems Byungjoon Min, Kwang-Il Goh, In-Mook Kim The negative feedback is well known to form the core of the genetic oscillatory systems. Although a negative feedback loop alone, such as the Repressilator, can produce sustained oscillations of protein concentrations, it is too noisier to ensure the robust oscillatory function, especially in the amplitudes manner. In addition, real genetic regulation circuits are formed a complex network constructed many coupled feedback structures. Here, we study dynamics of the coupled genetic oscillatory systems using exact stochastic simulation to extract simple rules for noise reduction in the oscillatory activities. we found the specific coupled structures reduce noise in the oscillations and the dynamics at the operator site is a key role for the noise in the oscillations. [Preview Abstract] |
Wednesday, March 17, 2010 2:54PM - 3:06PM |
T13.00003: Decoupling cellular memory from other gene expression characteristics Gabor Balazsi, Rhys Adams, Dmitry Nevozhay Non-conventional population level gene expression characteristics (such as the noise, cellular memory, skewness, modality, etc.) can have phenotypic impact and can affect cell population fitness independently of the gene expression mean. To study the phenotypic impact of gene expression characteristics other than the mean, they must be decoupled from the mean, and possibly from each other, i.e., two cell populations have to be established with similar means, but different non canonical gene expression characteristics. We study by experiment and mathematical modeling how positive feedback regulation can be used to decouple and adjust the cellular memory independently of the noise and the mean. We describe a state of ``population dynamic bistability'' where the cell population has bistable expression while individual cell lineages do not. Our results have implications for modeling gene expression bimodality and controlling cellular memory in cell populations. [Preview Abstract] |
Wednesday, March 17, 2010 3:06PM - 3:18PM |
T13.00004: Power Spectra of a Totally Asymmetric Simple Exclusion Process with Finite Resources L. Jonathan Cook, Royce K. P. Zia In a cell, a mRNA has only a finite number of ribosomes to use during protein synthesis. We take this constraint into account in the modeling of translation by a totally asymmetric simple exclusion process (TASEP). Through Monte Carlo simulations and analytical methods, we study the power spectrum of the total particle occupancy of the TASEP. New features are found, such as a severe suppression at low frequencies. We formulate a theory based on a linearized Langevin equation with discrete space and time. With good agreement between the theoretical approach and the simulations, we gain some insight in how finite resources affect a TASEP. [Preview Abstract] |
Wednesday, March 17, 2010 3:18PM - 3:30PM |
T13.00005: Power spectra in totally asymmetric simple exclusion process (TASEP) with local inhomogeneity Jiajia Dong, Royce K.P. Zia As a paradigmatic system in non-equilibrium statistical mechanics, TASEP has been extensively studied in the abstract and also applied to model many complex phenomena such as traffic flow and protein synthesis. We focus on a rather less studied aspect of TASEP: the total number of particles on a one-dimension open TASEP at time $t$, $N(t)$, and its power spectra $I(\omega)$, especially when there are local inhomogeneities. Motivated by the protein synthesis process where messenger RNA, codons and ribosomes are associated with the underlying lattice, sites and particles transported in TASEP, we investigate the effect on the power spectrum due to one defect (slower hopping rate) at different positions along the lattice. Using Monte Carlo simulation, we measure $I(\omega)$ for both the entire system and the subsystems separated by the defect. As in previous studies, oscillations are found. Here, however, more interesting characteristics emerge, depending on the location and the ``strength'' of the slow site. The biological implication of these results is also discussed. [Preview Abstract] |
Wednesday, March 17, 2010 3:30PM - 3:42PM |
T13.00006: Modeling of long DNA electrophoresis in inverse opals Nabil Laachi, Kevin Dorfman We investigate the electrophoretic motion of long DNA molecules in periodic geometries with a spherical confinement. The confining spheres, also called lakes, are spatially organized in a cubic, crystal-like lattice whereby DNA can only travel between spheres through narrow holes connecting them, also called straits. When the radius of the spheres exceeds the radius of gyration of the molecules, an entropic trapping-like mechanism is well suited to describe the dynamics of the chain. In the context of this study, however, we consider confining spheres with a radius on the order of a few Kuhn segments, so that chains can simultaneously span a fluctuating number of lakes. Adjacent spheres can then exchange segments through the straits, resulting in a net motion of the center of mass of the chain when an electric field is applied. In this study, we model the sequential exchange of segments -or translocation events- between neighboring lakes as a discrete stochastic chemical reaction. We employ kinetic Monte Carlo methods combined with free energy calculations to monitor the lake occupancies. Results on the chain mobility as a function of various parameters at play will be presented. [Preview Abstract] |
Wednesday, March 17, 2010 3:42PM - 3:54PM |
T13.00007: Spatiotemporal regulation of chemical reaction kinetics of cell surface molecules by active remodeling of cortical actin Bhaswati Bhattacharyya, Abhishek Chaudhuri, Kripa Gowrishankar, Satyajit Mayor, Madan Rao Cell surface proteins such as lipid tethered GPI-anchored proteins and Ras-proteins are distributed as monomers and nanoclusters on the surface of living cells. Recent work from our laboratory suggests that the spatial distribution and dynamics of formation and breakup of these nanoclusters is controlled by the active remodeling dynamics of the underlying cortical actin. To explain these observations, we propose a novel mechanism of nanoclustering, involving the transient binding to and advection along constitutively occuring ``asters'' of cortical actin. Here we study the consequences of such active actin based clustering, in the context of chemical reactions involving conformational changes of cell surface proteins. We find that active remodeling of cortical actin, can give rise to a dramatic increase in the reaction efficiency and output levels. In general, such actin driven clustering of membrane proteins could be a cellular mechanism to spatiotemporally regulate and amplify local chemical reaction rates, in the context of signalling and endocytosis. [Preview Abstract] |
Wednesday, March 17, 2010 3:54PM - 4:06PM |
T13.00008: Statistical analysis of trypanosomes' motility Vasily Zaburdaev, Sravanti Uppaluri, Thomas Pfohl, Markus Engstler, Holger Stark, Rudolf Friedrich Trypanosome is a parasite causing the sleeping sickness. The way it moves in the blood stream and penetrates various obstacles is the area of active research. Our goal was to investigate a free trypanosomes' motion in the planar geometry. Our analysis of trypanosomes' trajectories reveals that there are two correlation times - one is associated with a fast motion of its body and the second one with a slower rotational diffusion of the trypanosome as a point object. We propose a system of Langevin equations to model such motion. One of its peculiarities is the presence of multiplicative noise predicting higher level of noise for higher velocity of the trypanosome. Theoretical and numerical results give a comprehensive description of the experimental data such as the mean squared displacement, velocity distribution and auto-correlation function. [Preview Abstract] |
Wednesday, March 17, 2010 4:06PM - 4:18PM |
T13.00009: Stochastic Auto-regulation Models and Mixed Poisson Distributions therein Srividya Iyer-Biswas, C. Jayaprakash In this work we study the interplay between stochastic gene expression and system design using simple stochastic models of auto-activation and auto-inhibition. Using the Poisson Representation, a technique whose usefulness in the context of non-linear gene regulation models we elucidate, we are able to write down exact, analytical results for these feedback models in steady state. We also use this representation to analyze the parameter-spaces and demarcate where qualitatively distinct types of distributions (bimodals, power-laws and so on) occur. Using our results, we reexamine how well the auto-inhibition and auto-activation models serve their conventional roles as paradigms for noise suppression, and noise exploitation through increased heterogeneity, respectively. [Preview Abstract] |
Wednesday, March 17, 2010 4:18PM - 4:30PM |
T13.00010: Optimal strategies for timekeeping in cells Andrew Mugler, Aleksandra Walczak, Chris Wiggins Intracellular ``clocks'' are constrained by the fact that the molecules which oscillate in number to keep time also intrinsically fluctuate in number. Information theory provides natural measures of the reliability with which the oscillatory signal can be extracted from this intrinsic ``noise'' and propagated to other species in the cell. For a simple stochastic clock model, in which a chemical species driven by oscillatory production regulates via copy number a second species, we compute the mutual information between time and copy number for both the regulating and regulated species. The latter requires the full time-dependent joint probability distribution over copy counts, for which we solve accurately and efficiently via eigenfunction expansion. The simplicity of the model permits powerful analytic predictions such as scalings of information with driving frequency and copy number. The efficiency of the computation permits numerical optimization of information over model parameters, revealing, e.g., that different regulation functions are optimal in different biologically relevant regimes. [Preview Abstract] |
Wednesday, March 17, 2010 4:30PM - 4:42PM |
T13.00011: Effects of Jamming on Nonequilibrium Transport Times through Biological and Artificial Nanochannels Anton Zilman, John Pearson, Golan Bel Many biological channels perform highly selective transport without direct input of metabolic energy and without transitions from a ``closed'' to an ``open'' state during transport. Mechanisms of selectivity of such channels serve as an inspiration for creation of artificial nanomolecular sorting devices and biosensors. To elucidate the transport mechanisms, it is important to understand the transport on the single molecule level in the experimentally relevant regime when multiple particles are crowded in the channel. We analyze the effects of interparticle crowding on the nonequilibrium transport times through a finite-length channel by means of analytical theory and computer simulations and apply the results to the explanation of the single molecule fluorescence microscopy experiments in artificial and biological nano-channels. [Preview Abstract] |
Wednesday, March 17, 2010 4:42PM - 4:54PM |
T13.00012: Regulation of Calcium signaling through spatial Organization Aman Ullah, Ghanim Ullah, Khalid Machaca, Peter Jung Calcium waves and signals in oocytes are produced and sustained by the release of Ca$^{2+}$ from the Endoplasmic Reticulum (ER) through clustered release channels. Changes in the spatial organization of calcium signaling effectors regulate the spatiotemporal features of the calcium signal as is e.g. observed during oocyte maturation. We report here how specific changes in the clustering of the calcium release channels in conjunction with physiologic alterations of other signaling effectors can affect a) the sensitivity of the signaling machinery to external factors, b) the time course of global intracellular signals and c), the speed and propagation range of intracellular calcium waves. [Preview Abstract] |
Wednesday, March 17, 2010 4:54PM - 5:06PM |
T13.00013: Defects and DNA replication Michel Gauthier, John Herrick, John Bechhoefer In higher organisms, DNA replication is initiated at distinct sites called replication origins, where pairs of replication forks begin to duplicate DNA bi-directionally outward from the origin site until they eventually coalesce with another fork. Unfortunately, defects along the DNA (such as single-strand DNA lesions or double-strand breaks) can slow, or even stall, replication forks. We introduce a master-equation formalism to study DNA replication kinetics in the presence of defects resulting from DNA damage and find a crossover between two regimes: a normal regime, where the influence of defects is local, and an initiation-limited regime. In the latter, defects have a global impact on replication, whose progress is set by the rate at which origins of replication are activated, or initiated. Normal, healthy cells have defect densities in the normal regime. Our model can explain an observed correlation between interorigin separation and rate of DNA replication. [Preview Abstract] |
Wednesday, March 17, 2010 5:06PM - 5:18PM |
T13.00014: DNA replication in yeast is stochastic Scott Cheng-Hsin Yang, Nicholas Rhind, John Bechhoefer Largely on the basis of a simple --- perhaps too simple --- analysis of microarray-chip experiments, people have concluded that DNA replication in budding yeast (\textit{S. cerevisiae}) is a nearly deterministic process, in which the position and activation time of each origin of replication is pre-determined. In this talk, we introduce a more quantitative approach to the analysis of microarray data. Applying our new methods to budding yeast, we show that the microarray data imply a picture of replication where the timing of origin activation is highly stochastic. We then propose a physical model (the ``multiple-initiator model") to account for the observed probability distributions of origin- activation timing. [Preview Abstract] |
Wednesday, March 17, 2010 5:18PM - 5:30PM |
T13.00015: Control of DNA replication by anomalous reaction-diffusion kinetics John Bechhoefer, Michel Gauthier DNA replication requires two distinct processes: the initiation of pre-licensed replication origins and the propagation of replication forks away from the fired origins. Experiments indicate that these origins are triggered over the whole genome at a rate $I(t)$ (the number of initiations per unreplicated length per time) that increases throughout most of the synthesis (S) phase, before rapidly decreasing to zero at the end of the replication process. We propose a simple model for the control of DNA replication in which the rate of initiation of replication origins is controlled by protein-DNA interactions. Analyzing recent data from \textit{Xenopus} frog embryos, we find that the initiation rate is reaction limited until nearly the end of replication, when it becomes diffusion limited. Initiation of origins is suppressed when the diffusion-limited search time dominates. To fit the experimental data, we find that the interaction between DNA and the rate-limiting protein must be subdiffusive. [Preview Abstract] |
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