Bulletin of the American Physical Society
2006 APS March Meeting
Monday–Friday, March 13–17, 2006; Baltimore, MD
Session Y29: Focus Session: Noise and Fluctuation in Biological Systems |
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Sponsoring Units: DBP DPOLY Chair: Gabor Balazsi, Boston University Room: Baltimore Convention Center 326 |
Friday, March 17, 2006 8:00AM - 8:12AM |
Y29.00001: How stability can lead to variability: An example from eukaryotic gene expression Gabor Balazsi, William Blake, Farren Isaacs, Kevin Murphy, James J. Collins Eukaryotic genes have the potential for transcriptional reinitiation, resulting in repeated rounds of transcription from a scaffold of proteins assembled near the promoter region. We use stochastic simulations and mathematics to analyze the effect of the promoter-scaffold stability on gene expression noise for various steady-state levels of induction. In agreement with experimental observations, we find that decreasing transcription scaffold stability results in lower levels of noise at the protein level. We track the cause of this decrease through mRNA expression down to the level of an engineered GAL1 promoter. [Preview Abstract] |
Friday, March 17, 2006 8:12AM - 8:24AM |
Y29.00002: How stability can lead to variability: Induction timecourse of a eukaryotic gene William Blake, Gabor Balazsi, Farren Isaacs, Kevin Murphy, Yina Kuang, David R. Walt, James J. Collins Using an engineered GAL1 promoter as a model, we study the effect of the promoter-scaffold stability on the mean and noise of gene expression during an induction timecourse. In agreement with experimental observations, we find that decreasing transcription scaffold stability results in slower buildup of protein product and lower levels of noise at the protein level. This is a consequence of ``transcriptional bursting,'' observed in the simulations as well as experiment, where optical fiber-based technology was used to monitor induction timecourses in individual cells. [Preview Abstract] |
Friday, March 17, 2006 8:24AM - 8:36AM |
Y29.00003: Origins of extrinsic variability in eukaryotic gene expression Natalie Ostroff, Dmitri Volfson, Jennifer Marciniak, William J. Blake, Lev S. Tsimring, Jeff Hasty Variable gene expression within a clonal population of cells has been implicated in a number of important processes including mutation and evolution, determination of cell fates and the development of genetic disease. Recent studies have demonstrated that a significant component of expression variability arises from extrinsic factors thought to influence multiple genes in concert, yet the biological origins of this extrinsic variability have received little attention. Here we combine computational modeling with fluorescence data generated from multiple promoter-gene inserts in {\em Saccharomyces cerevisiae} to identify two major sources of extrinsic variability. One unavoidable source arising from the coupling of gene expression with population dynamics leads to a ubiquitous noise floor in expression variability. A second source which is modeled as originating from a common upstream transcription factor exemplifies how regulatory networks can convert noise in upstream regulator expression into extrinsic noise at the output of a target gene. Our results highlight the importance of the interplay of gene regulatory networks with population heterogeneity for understanding the origins of cellular diversity. [Preview Abstract] |
Friday, March 17, 2006 8:36AM - 9:12AM |
Y29.00004: Noisy cellular decision-making: from temporal to spatial choices Invited Speaker: |
Friday, March 17, 2006 9:12AM - 9:24AM |
Y29.00005: Absolute Rate Theories of Epigenetic Stability Aleksandra M. Walczak, Jose N. Onuchic, Peter G. Wolynes Spontaneous switching events in most characterized genetic switches are rare, resulting in extremely stable epigenetic properties. We show how simple arguments lead to theories of the rate of such events much like the absolute rate theory of chemical reactions corrected by a transmission factor. Both the probability of the rare cellular states that allow epigenetic escape, and the transmission factor, depend on the rates of DNA binding and unbinding events and on the rates of protein synthesis and degradation. Different mechanisms of escape from the stable attractors occur in the nonadiabatic, weakly adiabatic and strictly adiabatic regimes, characterized by the relative values of those input rates. [Preview Abstract] |
Friday, March 17, 2006 9:24AM - 9:36AM |
Y29.00006: Noise and correlations in genes silenced by small RNA. Terence Hwa, Erel Levine Many small regulatory RNAs have been identified in prokaryotes and eukaryotes in recent years. In many cases, RNA regulation is found in critical pathways. These include stress response and quorum sensing pathways in bacteria, and cell differentiation and programmed cell death in eukaryotes. In many cases, regulation by small RNA is used in switching off a response program as long as it is not required, allowing for a fast switching on when necessary. Clearly, accidental execution of such a program may bare grave consequences on the cell, and should be avoided. Here we analyze a stochastic model for gene regulation by the most abundant class of small RNA in bacteria. This class of small RNAs acts by base pairing with target mRNAs, silencing its translation and actively promoting its degradation. Importantly, the small RNA molecule is not recycled. Our model suggests that genes silenced by sRNA exhibits smooth noise, as opposed to the bursty noise characteristic to genes repressed at the level of transcription, with coupling between intrinsic noise and global, extrinsic fluctuations. In addition, we investigate how noise propagates through the indirect coupling between different targets of the same sRNA. These features are discussed in the context of circuits exhibiting multi-stability, where protein bursts have strong implications on spontaneous switching. [Preview Abstract] |
Friday, March 17, 2006 9:36AM - 9:48AM |
Y29.00007: A model for codon position bias in RNA editing Ralf Bundschuh, Tsunglin Liu RNA editing can be crucial for the expression of genetic information via inserting, deleting, or substituting a few nucleotides at specific positions in an RNA sequence. Within coding regions in an RNA sequence, editing usually occurs with a certain bias in choosing the positions of the editing sites. In the mitochondrial genes of {\it Physarum polycephalum}, many more editing events have been observed at the third codon position than at the first and second, while in some plant mitochondria the second codon position dominates. Here we propose an evolutionary model that explains this bias as the basis of selection at the protein level. The model predicts a distribution of the three positions rather close to the experimental observation in {\it Physarum}. This suggests that the codon position bias in {\it Physarum} is mainly a consequence of selection at the protein level. [Preview Abstract] |
Friday, March 17, 2006 9:48AM - 10:00AM |
Y29.00008: From Asymmetric Exclusion Processes to Protein Synthesis Jiajia Dong, Beate Schmittmann, Royce K.P. Zia Protein production rates are clearly vital for all biological systems. Thus, there is considerable interest in understanding the origins of these rates, as well as in manipulating them, especially for physiological and pharmaceutical applications. Since some codons are ``fast'' and others ``slow,'' we propose to exploit these differences and modify the production rate for any specific protein by replacing codons in the associated mRNA by their synonymous counterparts. As an illustration, we study a simple model of protein production: the one-dimensional driven lattice gas, also known as the totally asymmetric simple exclusion process (TASEP). We investigate systematically the effects on the overall current (the protein production rate) of having one or two slow/fast sites (i.e., codons) in an otherwise homogeneous lattice. The currents show a non-trivial dependence on the location of a single ``defect'' as well as on the separation between two defects. We discuss the implications for more realistic models of protein production. [Preview Abstract] |
Friday, March 17, 2006 10:00AM - 10:12AM |
Y29.00009: Intrinsic Fluctuations, Robustness and Tunability in Signaling Cycles. Joseph Levine, Hao Yuan Kueh, Leonid Mirny Covalent modification cycles (e.g. phosphorylation) underlie most cellular signaling. Low molecular copy number, arising from compartmental segregation and slow diffusion between compartments, potentially renders these cycles vulnerable to intrinsic chemical fluctuations. How can a cell operate reliably in the presence of this inherent stochasticity? How do changes in extrinsic parameters lead to variability of response? Can cells exploit these parameters to tune cycles to different ranges of stimuli? We study the dynamics of an isolated phosphorylation cycle. Our model shows that the cycle transmits information reliably if it is tuned to an optimal parameter range, in spite of intrinsic fluctuations and even for small input signal amplitudes. At the same time, the cycle is sensitive to changes in the concentration and activity of kinases and phosphatases. This sensitivity can lead to significant cell-to-cell response variability Our results show that signaling cycles possess a surprising combination of robustness and tunability. This combination makes them ubiquitous in eukaryotic signaling, optimizing signaling in the presence of fluctuations using their inherent flexibility. On the other hand, cycles tuned to suppress intrinsic fluctuations can be fragile to changes in the number and activity of kinases and phosphatases. Such trade-offs in robustness to fluctuations can influence the evolution of signaling cascades, making them the weakest links in cellular circuits. [Preview Abstract] |
Friday, March 17, 2006 10:12AM - 10:48AM |
Y29.00010: The Nature of Memory Objects in the Brain Invited Speaker: Our mind keeps a huge number of memories. We discuss here the number \textit{M} of neurons which must be implied in one primal memory object (the smell of a rose). We find that (in a storage area which is not genetically designed) spatial and connectivity requirements impose that \textit{M} be \textit{very small} (of the order of 3). We then extend these considerations to associative memories (where the smell of a rose evokes the color of a rose). [Preview Abstract] |
Friday, March 17, 2006 10:48AM - 11:00AM |
Y29.00011: Resource allocation in neural networks for motor control J. Milton, J. Cummins, J. Gunnoe, M. Tollefson, J.L. Cabrera, T. Ohira Multiplicative noise plays an important part of a non-predictive control mechanism for stick balancing at the fingertip. However, intentionally-directed movements are also used in stick balancing, particularly by beginners. The interplay between intentional and non-predictive control mechanisms for stick balancing was assessed using two dual task paradigms: the subject was asked to either move one of their legs rhythmically or to imagine moving their leg while balancing a stick (55.4 cm, 35 g) at their fingertip. Performance was measured by determining the stick survival function, i.e. the fraction of trials (total $\ge 25)$ for which the stick remained balanced at time t as a function of t. Performance was increased by concurrent rhythmic leg movements (50{\%} survival time shifted from 8-9s to 15s in a typical subject). Imagined movements resulted in a similar improvement (50{\%} survival time of 20s for the above subject) suggesting that this enhancement is not simply related to mechanical vibrations of the fingertip induced by leg movement. These observations emphasize the importance of the development of mathematical models for neural control of skilled motor movements that take into resource allocation of limited resources, such as intention. [Preview Abstract] |
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