Bulletin of the American Physical Society
2009 APS March Meeting
Volume 54, Number 1
Monday–Friday, March 16–20, 2009; Pittsburgh, Pennsylvania
Session W39: Quantitative Biology |
Hide Abstracts |
Sponsoring Units: DBP Chair: Michael Deem, Rice University Room: 411 |
Thursday, March 19, 2009 11:15AM - 11:27AM |
W39.00001: Synchrony in embryogenesis via an active medium R. Scott McIsaac, Anirvan Sengupta, Ned Wingreen In developing embryos of the frog \emph{Xenopus}, mitotic divisions occur at 8-minute intervals. After the initial rounds of division, nuclei divide in near-perfect synchrony throughout the embryo. Given a typical protein diffusion constant of $10 \frac{\mu m^2}{sec}$, and an embryo length of $\approx 1mm$, it would take diffusion many hours to propagate a signal across the embryo. Therefore, synchrony cannot be attained by diffusion alone. We hypothesize that known autocatalytic reactions of cell-cycle components make the embryo an ``active medium'' in which waves propagate much faster than diffusion, enforcing synchrony. Furthermore, developing embryos are found to be very robust, meaning that their spatial and temporal patterns are highly repeatable over a broad range of environmental conditions and despite biochemical noise. We report on robust synchronization of oscillations for a coupled two-species system consisting of diffusing activator and repressor molecules. [Preview Abstract] |
Thursday, March 19, 2009 11:27AM - 11:39AM |
W39.00002: Cell migration on ridges and cliffs Meghan Driscoll, Colin McCann, Rael Kopace, John Watts, Tess Homan, Wolfgang Losert The amoeba \textit{Dictyostelium discoideum} is a model system for the study of cellular migration, an important physiological process that occurs in embryonic development, wound healing, and cancer metastasis. We study the motion of \textit{D. discoideum} on surfaces with various topographies, particularly those that affect the direction of cellular migration. Topographical features, such as ridges and cliffs, were fabricated using multiphoton absorption polymerization. As the cells encountered these topographical features, we tracked their overall motions and shapes, as well as the locations and intensities of certain intracellular signals. We found that when cells undergoing chemokinesis, random migration in response to a chemical signal, encounter a ridge, they tend to move along that ridge, even if the ridge is shorter than the cell. When cells undergoing chemotaxis, directed migration in response to a chemical signal, are directed off of a cliff, they do not fall off the cliff. Instead, they search for new attachment points, eventually change direction, and continue moving along the edge of the cliff. Both ridges and cliffs affect more than just the motion of a cell; they also affect its shape. [Preview Abstract] |
Thursday, March 19, 2009 11:39AM - 11:51AM |
W39.00003: ABSTRACT WITHDRAWN |
Thursday, March 19, 2009 11:51AM - 12:03PM |
W39.00004: Mutational robustness emerges in a microscopic model of protein evolution Konstantin Zeldovich, Eugene Shakhnovich The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. We use a computational model of organismic evolution [Zeldovich et al, PLOS Comp Biol 3(7):e139 (2007)], which explicitly couples protein physics and population dynamics, to study mutational robustness of evolved model proteins. We compare evolved sequences with the ones designed to fold into the same native structures and having the same thermodynamic stability, and find that evolved sequences are more robust against point mutations, being less likely to be destabilized, and more likely to increase stability upon a point mutation. These results point to sequence evolution as an important method of protein engineering if mutational robustness of the artificially developed proteins is desired. On the biological side, mutational robustness of proteins appears to be a natural consequence of the divergence-mutation- selection evolutionary process. [Preview Abstract] |
Thursday, March 19, 2009 12:03PM - 12:15PM |
W39.00005: Kinetics of Slow Axonal Transport and Shape of Axon Peter Jung, Chen Ying, Yinyun Li, Anthony Brown The mechanical integrity of the axon in mature axons is provided by neurofilaments(NF). NFs move through the axon at the average slow rate of $0.5$mm/day, characterized by bursts of movement and extended pauses in between. The local number of NFs determines the local axonal caliber and as a result, the kinetics of NF movement determines the overall shape of the axon. We developed a kinetic model for movement of NFs based on live cell-imaging (J Neurosci. 2007,27:507, Mol Biol Cell. 2005, 16:4243). We use this model to predict changes in axonal morphology upon local modifications of the kinetics by e.g. factors released by myelin. [Preview Abstract] |
Thursday, March 19, 2009 12:15PM - 12:27PM |
W39.00006: Group behavior in cell migration Wolfgang Losert, Carole Parent, Colin McCann Cell migration up an external chemical gradient is a crucial element in many biological processes, such as embryogenesis and cancer metastasis. The aim of our study is to quantify chemotaxis of groups of cells. We find that at high cell densities (i.e. low cell-cell distances) cells migrate together in streams either spontaneously or in response to an externally applied chemical gradient. Analysis of cell tracks outside and within streams shows that cells do not speed up or slow down when moving as a group. In addition the persistence of motion appears unaffected by the formation of streams. At large cell-cell distances cells do not form streams in response to externally applied chemical gradients, and fewer cells move. At very low cell plating density cells are unable to respond to a chemical signal, even close to the signal source. We confirm that this lack of motion is not due to signal relay. Our results indicate that a quorum sensing mechanism exists which is closely coupled to chemotaxis. [Preview Abstract] |
Thursday, March 19, 2009 12:27PM - 12:39PM |
W39.00007: Effect of Recombination in the Evolutionary Dynamics of HIV under the Surveillance of Immune System Weiqun Peng, Wenjing Yang, Guanyu Wang Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), which has become one of the most destructive pandemics in history. The fact that HIV virus evolves very fast plays a central role in AIDS immunopathogenesis and the difficulty we face in finding a cure or a vaccine for AIDS. A distinguishing feature of HIV is its high frequency of recombination. The effect of recombination in the HIV evolution is not clear. We establish a mathematical model of the evolutionary dynamics. This model incorporates both point mutation and recombination for genetic diversity, and employs a fitness function developed by Wang and Deem (PRL 97, 188106, 2006) that accounts for the effect of immune system. Using this model, we explore the role of recombination in the battle between the virus population and the immune system, with a special focus on the condition under which recombination helps the virus population to escape from the immune system. [Preview Abstract] |
Thursday, March 19, 2009 12:39PM - 12:51PM |
W39.00008: A collective mechanism for phase variation in biofilms Nicholas Chia, Carl Woese, Nigel Goldenfeld Understanding how microbes gather into biofilm communities and maintain diversity remains one of the central questions of microbiology, requiring an understanding of microbes as communal rather then individual organisms. Phase variation plays an integral role in the formation of diverse phenotypes within biofilms. We propose a collective mechanism for phase variation based on gene transfer agents, and apply the theory to predict the population structure and growth dynamics of a biofilm. Our results describe quantitatively recent experiments, with the only adjustable parameter being the rate of intercellular horizontal gene transfer. Our approach derives from a more general picture for the emergence of cooperation between microbes. [Preview Abstract] |
Thursday, March 19, 2009 12:51PM - 1:03PM |
W39.00009: ABSTRACT WITHDRAWN |
Thursday, March 19, 2009 1:03PM - 1:15PM |
W39.00010: $\lambda$-prophage induction modeled as a cooperative failure mode of lytic repression Nicholas Chia, Ido Golding, Nigel Goldenfeld We analyze a system-level model for lytic repression of $\lambda$-phage in {\it E. coli\/} using reliability theory, showing that the repressor circuit comprises 4 redundant components whose failure mode is prophage induction. Our model reflects the specific biochemical mechanisms involved in regulation, including long-range cooperative binding, and its detailed predictions for prophage induction in {\it E. coli\/} under ultra-violet radiation are in good agreement with experimental data. [Preview Abstract] |
Thursday, March 19, 2009 1:15PM - 1:27PM |
W39.00011: Statistical Physics of Vaccine Design Michael Deem I will define a new parameter to quantify the antigenic distance between two H3N2 influenza strains. I will use this parameter to measure antigenic distance between circulating H3N2 strains and the closest vaccine component of the influenza vaccine. For the data between 1971 and 2004, the measure of antigenic distance correlates better with efficacy in humans of the H3N2 influenza A annual vaccine than do current state of the art measures of antigenic distance such as phylogenetic sequence analysis or ferret antisera inhibition assays. I suggest that this measure of antigenic distance can be used to guide the design of the annual flu vaccine. I will describe combining this measure of antigenic distance with a multiple-strain avian influenza transmission model to study the threat of simultaneous introduction of multiple avian influenza strains. For H3N2 influenza, the model is validated against observed viral fixation rates and epidemic progression rates from the World Health Organization FluNet - Global Influenza Surveillance Network. I find that a multiple-component avian influenza vaccine is helpful to control a simultaneous multiple introduction of bird-flu strains. I introduce Population at Risk (PaR) to quantify the risk of a flu pandemic, and calculate by this metric the improvement that a multiple vaccine offers. [Preview Abstract] |
Thursday, March 19, 2009 1:27PM - 1:39PM |
W39.00012: Spatial coordination in memrane proximal signaling in T-cells Maxim N. Artyomov, Mieszko Lis, Arup Chakraborty Membrane-proximal signaling initiates signaling networks of the T-cell which ultimately lead to the T-cell activation. Signal formation requires assembly of the several membrane proteins and successful cooperative interactions inside the complex. Diffusion and chemical reactions involved in the process are characterized by substantially different timescales. In this work we consider how the reaction-diffusion system described by the wide spectrum of timescales can be selective for the minute amounts of the signal (cognate peptide-MHC complex) over the large amounts of irrelevant targets (non-cognate peptide-MHC complex). Note that single distinction between relevant and irrelevant targets - the affinity to the T-cell receptor, is nonetheless sufficient to discriminate between two groups of targets. Moreover, proposed mechanism allows for signal cooperativity with non-cognate peptides amplifying the signal from cognate ones even though they can not signal by themselves. This kind of cooperativity has been observed in recent experiments. [Preview Abstract] |
Thursday, March 19, 2009 1:39PM - 1:51PM |
W39.00013: Digital signaling, signal filters and central tolerance in thymocytes Ashok Prasad, Julie Zikherman, Jayajit Das, Jeroen Roose, Arthur Weiss, Arup Chakraborty T cells are characterized by the immense diversity of the antigen binding receptors (TCR's) they bear. TCR's carried by immature T cells (thymocytes) are made in the thymus by a stochastic process, followed by testing against self-peptides. Thymocytes that do not respond to self-peptides die through neglect (positive selection); those that respond too strongly die through apoptosis (negative selection). We present a new molecular explanation of this phenomenon via a computational model, which we also test by experiments. We show that Ras activation in thymocytes is characterized by the presence of a digital molecular switch due to a positive feedback loop in a Ras-activating enzyme. We also show how an important adaptor protein, LAT, acts as a filter, sending weak TCR signals along a pathway that leads to Ras activation via a graded mechanism, and sending stronger signals along another path that activates Ras via the molecular switch. Our model yields a new mechanism for digital signaling of the Erk protein in mammalian cells, and has important implications for autoimmunity. [Preview Abstract] |
Thursday, March 19, 2009 1:51PM - 2:03PM |
W39.00014: A biophysical model of prokaryotic diversity in geothermal hot springs Suzanne Amador Kane, Anna Klales, James Duncan, Elizabeth Janus Nett Photosynthetic bacteria living in geothermal hot spring environments have surprisingly complex ecosystems with an unexpected level of genetic diversity. In particular, their thermal gradients support genetically distinct bacterial strains that differ in their preferred temperatures for reproduction and photosynthesis. Each region along the thermal gradient exhibits multiple strains of photosynthetic bacteria adapted to several distinct thermal optima, rather than the expected single thermal strain adapted to the local environmental temperature. Here we analyze microbiology data from several ecological studies to show that the thermal distribution field data exhibit several universal features independent of location and specific bacterial strain. These include the distribution of optimal temperatures of different thermal strains and the functional dependence of the net population density on temperature. We present a simple population dynamics model of these systems that explains the observed diversity of different strains of the photosynthetic bacteria, the observed thermal population distributions and certain features of population dynamics observed in laboratory studies of the same organisms. [Preview Abstract] |
Thursday, March 19, 2009 2:03PM - 2:15PM |
W39.00015: Understanding Original Antigenic Sin with a Dynamical System Keyao Pan, Michael Deem Original antigenic sin is the phenomenon in which prior exposure to an antigen leads to a subsequent suboptimal immune response to a related antigen. Immune memory normally allows for an improved and rapid response to antigens and is the mechanism by which vaccination works. We here develop a dynamical system model of the mechanism of original antigenic sin, clarifying and explaining the detailed spin-glass treatment of original antigenic sin [1]. The dynamical system describes the virus load as it propagates through healthy and infected cells, the naive and memory B cell concentrations, and the affinity of the immune response. Explicit correspondences between the microscopic variables of the spin-glass model and the dynamical system model will be given. The dynamical system model reproduces the phenomenon of original antigenic sin, and describes how competition between different B-cells compromises the overall effect of the immune system. The trade off between the naive and memory immune responses as a function of antigenic distance between the initial and subsequent antigens is displayed. A suboptimal immune response, the original antigenic sin, is observed for intermediate antigenic distances. [1] Deem MW, Lee H-Y. Sequence space localization in the immune system response to vaccination and disease. Phys Rev Lett 2003;91:068101. [Preview Abstract] |
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