Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session C36: Statistical Physics of Large Populations of Cells: from Microbes to Tissues IInvited
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Sponsoring Units: DBIO Chair: Ned Wingreen, Princeton University Room: BCEC 205C |
Monday, March 4, 2019 2:30PM - 3:06PM |
C36.00001: A unifying theory of branching morphogenesis Invited Speaker: Benjamin Simons Branching morphogenesis has been a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how the macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Here we show that, in the mouse mammary gland, kidney and pancreas, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on large-scale organ reconstructions, genetic lineage tracing and proliferation kinetics, we show that morphogenesis follows from the collective proliferative activity of sublineage-restricted equipotent self-renewing progenitors localized at ductal tips that drive a process of ductal elongation and stochastic tip bifurcation. By correlating ductal termination with proximity to maturing ducts, this dynamics results in the specification of a complex network of defined density and statistical organization. These results show that branched epithelial structures in mammalian tissues develop as a self-organized process, reliant upon a strikingly simple, but generic, set of local rules, without recourse to a rigid and deterministic sequence of genetically programmed events. |
Monday, March 4, 2019 3:06PM - 3:42PM |
C36.00002: Diversity, dynamics and defense in microbial communities Invited Speaker: Devaki Bhaya Cyanobacteria are an ancient group of microbes that can carry out photosynthesis and nitrogen fixation. They are important members of microbial communities in terrestrial and aquatic environments. They thrive in moderate and harsh environments where they can adapt to desiccation stress and extremes of heat or cold. For several years we have focused on extremophile communities that form stratified biofilms or microbial mats in the hot springs of Yellowstone National Park. In these communities, 16S rRNA diversity has been correlated with environmental gradients of temperature and light. The genomes of two Synechococcus isolates that dominate at different temperatures in the mats, has provided key insights into genomic and metabolic diversity within these populations. Metagenomic data in combination with deep amplicon sequencing from these communities, revealed an unexpectedly high degree of genomic micro-diversity. We have also attempted to explore the co-evolution of host and cyanophage populations in the microbial mats, by creating viromes and exploiting CRISPR spacer information. Finally, we are also interested in probing the importance of phototaxis and motility in these structured communities. I will describe our findings in the context of how these moderately complex communities are ideally suited to probing how physical forces and chemical gradients in combination with genetic diversity shape microbial community structure and organization. The future of modeling complex interactions and the ability to test hypotheses in synthetic communities will be explored. |
Monday, March 4, 2019 3:42PM - 4:18PM |
C36.00003: Coevolutionary dynamics in the immune system Invited Speaker: Armita Nourmohammad The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by engaging in a coevolutionary arms race with the adaptive immune system: The B-cell receptors in the adaptive immune system diversify to neutralize the virus and HIV evolves to evade the immune response. While it is clear that HIV exerts strong selection on the adaptive immune system, the modes of immune response are still unknown. Here I introduce a non-equilibrium framework to characterize the rapid coevolution of immune cells and pathogens. By tracing the immune repertoire of HIV patients over time and reconstructing the history of the accumulated mutations within patients, I show evidence for strong co-adaptation of the immune repertoire and HIV. I argue that rapid affinity maturation of the immune system upon viral expansion and a quasi-stationary response during chronic infection characterize the B-cell response to HIV. |
Monday, March 4, 2019 4:18PM - 4:54PM |
C36.00004: Cooperative growth and cell-cell aggregation in marine bacteria Invited Speaker: Otto X Cordero Bacterial cooperation, whereby cells secrete compounds that can facilitate the growth of neighboring cells, has been extensively studied through the lens of evolutionary biology. However, the environmental implications of cooperation and the ecological scenarios under which it takes place remain much less understood. In this talk I will discuss the conditions under which cooperative growth emerges in microbial populations that degrade complex organic materials in the ocean. I will show that organisms that are poor secretors of hydrolytic enzymes use chemotactic behavior to form cell-cell aggregates that enable individuals to increase local concentrations and efficiently uptake the solubilized organic matter. By contrast, when organisms secrete highly active enzymes dynamics turn competitive, cells avoid aggregation and the efficiency of carbon uptake drops. I will discuss the theoretical limits of aggregation and how bacterial isolates from the ocean can overcome these limits in the laboratory by developing multicellular behaviors. I will back up these results with theory, data from individual based models and experiments with natural isolates. Finally, I will discuss the potential role of social cheaters in the natural environment, based on a study with hundreds of micro-scale particle colonization experiments in natural seawater. |
Monday, March 4, 2019 4:54PM - 5:30PM |
C36.00005: How adaptive immunity constrains the composition and fate of large bacterial populations Invited Speaker: Sidhartha Goyal Features of the CRISPR-Cas system, in which bacteria integrate small segments of phage genome (spacers) into their DNA to neutralize future attacks, suggest that its effect is not limited to individual bacteria but may control the fate and structure of whole populations. Emphasizing the population-level impact of the CRISPR-Cas system, recent experiments show that some bacteria regulate CRISPR-associated genes via the quorum sensing (QS) pathway. Here we present a model that shows that from the highly stochastic dynamics of individual spacers under QS control emerges a rank-abundance distribution of spacers that is time invariant, a surprising prediction that we test with dynamic spacer-tracking data from literature. This distribution depends on the state of the competing phage–bacteria population, which due to QS-based regulation may coexist in multiple stable states that vary significantly in their phage-to-bacterium ratio, a widely used ecological measure to characterize microbial systems. |
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