Bulletin of the American Physical Society
APS March Meeting 2018
Volume 63, Number 1
Monday–Friday, March 5–9, 2018; Los Angeles, California
Session R58: Controlling Space and Time in Biology: From Gene Regulation in a Single Cell to Pattern Formation in Cell Populations and DevelopmentInvited Session
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Sponsoring Units: DBIO Chair: Yuhai Tu, IBM T J Watson Research Center Room: LACC Petree Hall C |
Thursday, March 8, 2018 8:00AM - 8:36AM |
R58.00001: Taking the pulse of flagellum synthesis in a single bacterium Invited Speaker: Philippe Cluzel Synthesis and assembly of the bacterial flagellum in E. coli requires the coordinated transcription of over 40 different genes in 14 different operons. Experiments at the population level suggested that the expression of these genes followed a temporal cascade where each operon was sequentially activated in a well-defined order. However, by combining quantitative time-lapse microscopy with a microfluidic device that allows for individual lineage-tracking, we discovered that the dynamics of flagellar transcription in individual bacterium are highly heterogeneous: we found that transcription of flagellar genes fluctuated dramatically in slow stochastic pulses within a single cell, alternating between ‘on’ and ‘off’ periods that span over several generations. By examining the activity of pairs of promoters within the same cell, we find that during some transcriptional pulses only a specific subgroup of flagellar operons are expressed while during other pulses the full 14 operons are expressed simultaneously. We speculate that such pulsating dynamics confers a fitness advantage over continuous gene expression for maintaining a heterogeneous mixture of phenotypes within an isogenic population. |
Thursday, March 8, 2018 8:36AM - 9:12AM |
R58.00002: Induction and Entrainment of Glycolytic Oscillations in Single Yeast Cells Invited Speaker: Anna-Karin Gustavsson Oscillations are widely distributed in nature and synchronization of oscillators has been described at the cellular level (e.g. heart cells) and at the population level (e.g. fireflies). Yeast glycolysis is one of the best known oscillatory systems. However, it has been studied almost exclusively at the population level, and observations have thus been limited to average behavior in synchronized cultures. To determine the mechanisms behind oscillations, cell-cell interactions and synchronization, and to investigate the role of cell-cell heterogeneity, oscillations have to be studied on the single-cell level. In this work, we developed and combined a suite of methods to induce and study sustained glycolytic oscillations in individual yeast cells. These methods include optical tweezers for cell positioning, microfluidics for precise environmental control, and fluorescence microscopy as readout for metabolite concentration. Using this methodology, we identified the precise conditions required for oscillations to emerge in individual cells and elucidated the mechanism behind oscillations. We also investigated the mechanism behind cell-cell synchronization, its robustness to cell-cell heterogeneity, and its universality with respect to different types of external perturbations. |
Thursday, March 8, 2018 9:12AM - 9:48AM |
R58.00003: Adapt to oscillate: a nonequilibrium thermodynamic view of dynamic quorum sensing Invited Speaker: Lei-Han Tang Cell-density-dependent rhythmic behavior, or dynamic quorum sensing, has been suggested to coordinate population level activities such as cell migration and embryonic development. Quantitative description of the oscillatory phenomenon is hitherto hampered by incomplete knowledge of the underlying intracellular processes, especially when isolated cells appear to be quiescent. Here we present a nonequilibrium thermodynamic scenario where adaptive sensing drives the oscillation of a dissipative signaling field through stimulated energy release. We prove, on general grounds, that adaptation implies phase reversal of the linear response function in a certain frequency domain, in violation of the fluctuation-dissipation theorem (FDT) under restricted coupling between a cell and the signal[1]. Consequently, at sufficiently strong coupling, an oscillating signal in a suitable frequency range becomes self-sustained due to the energy outflow from adaptive cells. We find this overarching principle to be at work in several natural and synthetic oscillatory systems, and it may help to guide the design of further experiments on glycolytic oscillation in yeast suspensions[2]. |
Thursday, March 8, 2018 9:48AM - 10:24AM |
R58.00004: Reverse engineer spatial patterns in biology Invited Speaker: Chao Tang Precise and robust patterns emerge in biology, especially during development. Dissecting the genetic interactions that lead to these patterns has been the corner stone in developmental biology. This is usually done by observing changes in the pattern when perturbing the system, e.g. by deletions and/or mutations of the genes. Mathematical modeling usually starts with the knowledge of the genetic network inferred from those kinds of experiments. Here we set out to try a different and hopefully complementary approach. We ask the question that given a pattern what are the possible interactions or regulation logic that can achieve the pattern. In this talk, I will present examples of this approach using deep learning neural networks. In particular, I will discuss our results and lessons we learnt in the embryogenesis of fruit flies. |
Thursday, March 8, 2018 10:24AM - 11:00AM |
R58.00005: Morphogen Gradient Reconstitution Reveals Hedgehog Pathway Design Principles Invited Speaker: Joseph S. Markson In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen- sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision remain unclear. Here, combining cell-based in vitro gradient reconstitution, genetic re-wiring, and mathematical modeling, we systematically analyzed the unique architectural features of the Sonic Hedgehog pathway. The combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared to alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes, and to compare the patterning behaviors of alternative, re-wired, pathway architectures offers a powerful way to understand and engineer multicellular patterning. |
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