Bulletin of the American Physical Society
APS March Meeting 2010
Volume 55, Number 2
Monday–Friday, March 15–19, 2010; Portland, Oregon
Session J11: Biological Networks & System Biology |
Hide Abstracts |
Sponsoring Units: DBP Chair: Lev Tsimring, University of California, San Diego Room: A107-A109 |
Tuesday, March 16, 2010 11:15AM - 11:27AM |
J11.00001: Synchronization of synthetic gene oscillators Lev S. Tsimring, Tal Danino, Octavio Mondragon-Palomino, Jeff Hasty Synchronized clocks are of fundamental importance in the coordination of rhythmic behavior among individual elements in a community. We describe an engineered gene circuit with intercellular coupling that generates synchronized oscillations in a population of bacteria. Using micro?uidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring on millimeter scales. We use computational modeling to quantitatively describe the observed phenomena. [Preview Abstract] |
Tuesday, March 16, 2010 11:27AM - 11:39AM |
J11.00002: ABSTRACT WITHDRAWN |
Tuesday, March 16, 2010 11:39AM - 11:51AM |
J11.00003: A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency Maxim Artyomov, Alex Meissner, Arup Chakraborty Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, pluripotent embryonic stem cells differentiate into diverse cell types that make up the organism (e.g., a human). There has long been an effort to make this process go backward -- i.e., reprogram a differentiated cell (e.g., a skin cell) to pluripotent status. Recently, this has been achieved by transfecting certain transcription factors into differentiated cells. This method does not use embryonic material and promises the development of patient-specific regenerative medicine, but it is inefficient. The mechanisms that make reprogramming rare, or even possible, are poorly understood. We have developed the first computational model of transcription factor-induced reprogramming. Results obtained from the model are consistent with diverse observations, and identify the rare pathways that allow reprogramming to occur. If validated, our model could be further developed to design optimal strategies for reprogramming and shed light on basic questions in biology. [Preview Abstract] |
Tuesday, March 16, 2010 11:51AM - 12:03PM |
J11.00004: Stochastic Polynomial Dynamic Models of the Yeast Cell Cycle Indranil Mitra, Elena Dimitrova, Abdul S. Jarrah In the last decade a new holistic approach for tackling biological problems, systems biology, which takes into account the study of the interactions between the components of a biological system to predict function and behavior has emerged. The reverse-engineering of biochemical networks from experimental data have increasingly become important in systems biology. Based on Boolean networks, we propose a time-discrete stochastic framework for the reverse engineering of the yeast cell cycle regulatory network from experimental data. With a suitable choice of state set, we have used powerful tools from computational algebra, that underlie the reverse-engineering algorithm, avoiding costly enumeration strategies. Stochasticity is introduced by choosing at each update step a random coordinate function for each variable, chosen from a probability space of update functions. The algorithm is based on a combinatorial structure known as the Gr\"{o}bner fans of a polynomial ideal which identifies the underlying network structure and dynamics. The model depicts a correct dynamics of the yeast cell cycle network and reproduces the time sequence of expression patterns along the biological cell cycle. Our findings indicate that the methodolgy has high chance of success when applied to large and complex systems to determine the dynamical properties of corresponding networks. [Preview Abstract] |
Tuesday, March 16, 2010 12:03PM - 12:15PM |
J11.00005: Pulse-transmission Oscillators: Autonomous Boolean Models and the Yeast Cell Cycle Volkan Sevim, Xinwei Gong, Joshua Socolar Models of oscillatory gene expression typically involve a constitutively expressed or positively autoregulated gene which is repressed by a negative feedback loop. In Boolean representations of such systems, which include the repressilator and relaxation oscillators, dynamical stability stems from the impossibility of satisfying all of the Boolean rules at once. We consider a different class of networks, in which oscillations are due to the transmission of a pulse of gene activation around a ring. Using autonomous Boolean modeling methods, we show how the circulating pulse can be stabilized by decoration of the ring with certain feedback and feed-forward motifs. We then discuss the relation of these models to ODE models of transcriptional networks, emphasizing the role of explicit time delays. Finally, we show that a network recently proposed as a generator of cell cycle oscillations in yeast contains the motifs required to support stable transmission oscillations. [Preview Abstract] |
Tuesday, March 16, 2010 12:15PM - 12:27PM |
J11.00006: Positional Information, in bits Julien Dubuis, William Bialek, Eric Wieschaus, Thomas Gregor Pattern formation in early embryonic development provides an important testing ground for ideas about the structure and dynamics of genetic regulatory networks. Spatial variations in the concentration of particular transcription factors act as ``morphogens,'' driving more complex patterns of gene expression that in turn define cell fates, which must be appropriate to the physical location of the cells in the embryo. Thus, in these networks, the regulation of gene expression serves to transmit and process ``positional information.'' Here, using the early Drosophila embryo as a model system, we measure the amount of positional information carried by a group of four genes (the gap genes Hunchback, Kr\"uppel, Giant and Knirps) that respond directly to the primary maternal morphogen gradients. We find that the information carried by individual gap genes is much larger than one bit, so that their spatial patterns provide much more than the location of an ``expression boundary.'' Preliminary data indicate that, taken together these genes provide enough information to specify the location of every row of cells along the embryo's anterior-posterior axis. [Preview Abstract] |
Tuesday, March 16, 2010 12:27PM - 12:39PM |
J11.00007: Redundancy and error resilience in Boolean networks Tiago Peixoto Gene regulation of evolved organisms is marked by a high degree of reliability, despite its intrinsically noisy nature. We model reliable gene regulation as Boolean networks with redundant functions, and with a noise parameter playing the role of temperature. We show that dynamics on those networks is marked by a dynamical phase transition from non-ergodicity to ergodicity, as noise is increased. We obtain a general upper bound on the maximum amount of noise sustainable by any Boolean network, as a function of the number of inputs per node.\\[4pt] Relevant literature: Redundancy and error resilience in Boolean Networks, Tiago P. Peixoto, arXiv:0909.1740v1 (2009) [Preview Abstract] |
Tuesday, March 16, 2010 12:39PM - 12:51PM |
J11.00008: Phospho-proteins patial gradients in a cell of spheroidal shape Gerardo Sosa, Guillermo Ramirez-Santiago Many signalling proteins undergo phosphorilated-dephosphorilated cycles at different locations inside the cell. These cycles give rise to spatial gradients of phosphoproteins. In this work we solve the reaction-difussion equation in a spheroidal geometry and investigate the diffusion of the phosphorilated form of the proteins to evaluate the size of the spatial gradients. This is done in terms of diffusion coefficients as well as protein kinase and phosphatase activities. Previous estimations of these gradients have been done for two geometries [1]: (i) a spherical cell and (ii) for a kinase and a protein each one located on two parallel planar membranes. This type of quantitative analyzes may have important implications in the cellular signaling processes [2].\\[4pt] [1] G.C. Brown, B.N. Kholodenko, FEBS Letters, vol. 457, p. 452-454\\[0pt] [2] B.N. Kholodenko, G.C. Brown, J.B. Hoek, Biochem. J. vol. 350, p. 901-907. [Preview Abstract] |
Tuesday, March 16, 2010 12:51PM - 1:03PM |
J11.00009: Noise and robustness in the cyanobacterial circadian oscillator David Lubensky Like humans and most higher animals, photosynthetic cyanobacteria possess an autonomous 24-hour circadian clock that allows them to anticipate daily changes in their environment. This oscillator is known to be extremely stable, with a correlation time on the order of 100 days in a single, isolated cell, even in the absence of any entraining signals from the environment. The origin of such remarkable robustness, however, remains mysterious. Here, we present a stochastic model of the biochemical circuitry underlying the clock, including both transcriptional feedback and the post-translational phosphorylation cycle that is thought to be the core oscillator. We find that the phosphorylation oscillator in isolation is highly resistant to the intrinsic noise associated with molecular discreteness, but that a growing, dividing cell is a considerably more challenging environment in which to sustain stable oscillations. We suggest that coupling the phosphorylation cycle to a clock based on delayed negative transcriptional feedback may substantially increase the robustness of both oscillators and detail how this enhancement comes about. [Preview Abstract] |
Tuesday, March 16, 2010 1:03PM - 1:15PM |
J11.00010: A ratchet mechanism for low-frequency hearing in mammals Tobias Reichenbach, A.J. Hudspeth The sensitivity and frequency selectivity of hearing result from tuned amplification by an active process in the mechanoreceptive hair cells. The nature of the active process in the mammalian cochlea is intensely debated, for outer hair cells exhibit two forms of mechanical activity, active hair-bundle motility and membrane-based electromotility. Here we show theoretically that active hair-bundle motility and electromotility can together implement an efficient mechanism for amplification that functions like a ratchet: sound-evoked forces acting on the basilar membrane are transmitted to the hair bundles while electromotility decouples the active hair-bundle forces from the basilar membrane. Through a combination of analytical and computational techniques we demonstrate that the ratchet mechanism can naturally account for a variety of unexplained experimental observations from low-frequency hearing. [Preview Abstract] |
Tuesday, March 16, 2010 1:15PM - 1:27PM |
J11.00011: Effects of the somatic electrical circuit on spontaneous mechanical oscillations of inner ear hair bundles Damien Ramunno-Johnson, C. Elliott Strimbu, Lea Fredrickson, Albert Kao, Dolores Bozovic Under \textit{in vitro} conditions, uncoupled hair bundles of the bullfrog (\textit{Rana catesbeiana}) sacculus have been shown to exhibit spontaneous oscillations. We used a high-speed complementary metal oxide semiconductor camera to track the movements of hundreds of cells in parallel from dozens of preparations. We found that innate bundle movements exhibit a complex profile with multiple periodicities. Experiments inhibiting the electrical resonance in the cell body show a strong effect on the mechanical oscillations of the hair bundles. This indicates that the electrical oscillation is coupled with the mechanical oscillations of the hair bundles. [Preview Abstract] |
Tuesday, March 16, 2010 1:27PM - 1:39PM |
J11.00012: Negative Feedback in the \textit{Vibrio harveyi} Quorum-Sensing Circuit Shu-Wen Teng, Jessie Schaffer, Ned Wingreen, Bonnie Bassler, Nai Phuan Ong Quorum sensing is the mechanism by which bacteria communicate and synchronize group behaviors. Multiple feedbacks have been identified in the model quorum-sensing bacterium \textit{Vibrio harveyi}, but it has been unclear how these feedbacks interact in individual cells to control the fidelity of signal transduction. We measured the copy number distribution of the master regulators to quantify the activity of the signaling network. We find that the feedbacks affect the production rate, level, and noise of the core quorum-sensing components. Using fluorescence time-lapse microscopy, we directly observed the master regulator in individual cells, and analyzed the persistence of heterogeneity in terms of the normalized time-delayed direct correlation. Our findings suggest that feedback from small regulatory RNAs regulates a receptor to control the noise level in signal transduction. We further tested this model by re-engineering the gene circuit to specifically diminish this feedback. We conclude that negative feedbacks mediated by sRNAs permit fine-tuning of gene regulation, thereby increasing the fidelity of signal transduction. [Preview Abstract] |
Tuesday, March 16, 2010 1:39PM - 1:51PM |
J11.00013: NF-$\kappa $B dynamics show digital activation and analog information processing in cells Savas Tay, Jake Hughey, Timothy Lee, Tomasz Lipniacki, Markus Covert, Stephen Quake Cells operate in ever changing environments using extraordinary communication capabilities. Cell-to-cell communication is mediated by signaling molecules that form spatiotemporal concentration gradients, which requires cells to respond to a wide range of signal intensities. We used high-throughput microfluidic cell culture, quantitative gene expression analysis and mathematical modeling to investigate how single mammalian cells respond to different concentrations of the signaling molecule TNF-$\alpha$ via the transcription factor NF-$\kappa $B. We measured NF-$\kappa$B activity in thousands of live cells under TNF-$\alpha $ doses covering four orders of magnitude. In contrast to population studies, the activation is a stochastic, switch-like process at the single cell level with fewer cells responding at lower doses. The activated cells respond fully and express early genes independent of the TNF-$\alpha $ concentration, while only high dose stimulation results in the expression of late genes. Cells also encode a set of analog parameters such as the NF-$\kappa $B peak intensity, response time and number of oscillations to modulate the outcome. We developed a stochastic model that reproduces both the digital and analog dynamics as well as the gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-$\alpha $ induced NF-$\kappa$B signaling in various types of cells. [Preview Abstract] |
Tuesday, March 16, 2010 1:51PM - 2:03PM |
J11.00014: Coherently amplified negative feedback loop as a model for NF-kappaB oscillations Jaewook Joo The cells secrets various signaling molecules as a response to an external signal and modulate its own signaling processes. The precise role of this autocrine and/or paracrine signaling on cell information processing is mostly unknown. We will present the effect of TNF alpha autocrine signaling on NF-kappaB oscillations, using a simplified model of coherently amplified negative feedback loop. We will discuss the bifurcation diagram (i.e., dose-response curve), especially the robustness and the tenability of the period of NF-kappaB oscillations. Finally, we will compare the results from the above model with those from a previous model of time-delayed negative feedback alone. [Preview Abstract] |
Tuesday, March 16, 2010 2:03PM - 2:15PM |
J11.00015: NFsim: A versatile rule-based simulator for complex biological systems Michael Sneddon, James Faeder, Thierry Emonet Traditional methods for biochemical reaction simulation require the enumeration of every possible molecular species and reaction channel, which can be tedious and often impossible for many large or complex systems. We have developed NFsim, a new software platform for exact stochastic simulation of large biochemical reaction networks. By using an agent-based representation of molecules and rules to define interactions, the performance of NFsim is independent of the size of the reaction network. Rates in NFsim can be defined as mathematical or conditional functions of the system to facilitate coarse-graining and general specification of complex models. Here we demonstrate NFsim's novel capabilities with general models of multi-site phosphorylation proteins, receptor signaling and aggregation in the immune system, actin filament assembly, and bacterial chemotaxis signaling. [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