Browsing by Author "Keymer, Juan E."

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    Diversity emerging: from competitive exclusion to neutral coexistence in ecosystems
    (2011) Keymer, Juan E.; Fuentes, Miguel A.; Marquet Iturriaga, Pablo Ángel
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    Ecological succession and the competition-colonization trade-off in microbial communities
    (2022) Wetherington, Miles T.; Nagy, Krisztina; Dér, László; Ábrahám, Ágnes; Noorlag, Janneke; Galajda, Peter; Keymer, Juan E.
    Background: During range expansion in spatially distributed habitats, organisms differ from one another in terms of their patterns of localization versus propagation. To exploit locations or explore the landscape? This is the competition-colonization trade-off, a dichotomy at the core of ecological succession. In bacterial communities, this trade-off is a fundamental mechanism towards understanding spatio-temporal fluxes in microbiome composition. Results: Using microfluidics devices as structured bacterial habitats, we show that, in a synthetic two-species community of motile strains, Escherichia coli is a fugitive species, whereas Pseudomonas aeruginosa is a slower colonizer but superior competitor. We provide evidence highlighting the role of succession and the relevance of this trade-off in the community assembly of bacteria in spatially distributed patchy landscapes. Furthermore, aggregation-dependent priority effects enhance coexistence which is not possible in well-mixed environments. Conclusions: Our findings underscore the interplay between micron-scale landscape structure and dispersal in shaping biodiversity patterns in microbial ecosystems. Understanding this interplay is key to unleash the technological revolution of microbiome applications.
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    Spatial biology of Ising-like synthetic genetic networks
    (2021) Simpson Alfaro, Kevin Matías; Federici, Fernán; Keymer, Juan E.; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    Understanding how spatially-correlated cellular states emerge from the local interaction of gene network dynamics is a fundamental challenge in biology. Short and long-range correlations and anti-correlations in gene expression can be found in spatially-distributed cellular systems such as eukaryotic tissues and microbial communities. However, the study of gene spatial correlations emerging from cell-cell coupling in natural systems is difficult since complex interactions are the norm. An alternative is to generate synthetic genetic networks (SGNs) that capture essential features of cell-cell interactions and reveal their influence in the emergence of cellular state patterns. Here, we combine synthetic biology, theoretical modelling and computational simulations to study the emergence of macroscopic gene correlations and address possible mechanisms for multi-scale self-organization of gene states in bacteria. We applied the Ising model as a theoretical framework to study the self-organization of spatially-correlated gene expression in two-state SGNs that are coupled by short-range chemical signals in E. coli. Inspired by the Ising model, we name these SGNs ferromagnetic or anti-ferromagnetic depending if they stabilize the same or the opposite state in neighboring cells. As predicted by our simulations that combine the two-dimensional Ising model with the Contact Process lattice model of cell population dynamics, these SGNs allowed the self-organization of spatial patterns of short and long-scale cellular state domains in bacterial colonies, where the size of the domains depends on the type of interaction, ferromagnetic or anti-ferromagnetic. The emergence of spatial correlations showed to be independent of the cell shape and the underpinning mechanical forces. The similarity found between ferromagnetic colonies and simulated ferromagnetic populations suggest these colonies are near the critical point of phase transition, implying that far regions in the colony are correlated. This work provides resources and a general scope theoretical framework that explain how both short and long-range correlations (and anti-correlations) are able to self-organize from locally-interacting networks. These results on multi-scale organization of gene network states shed light onto the study of pattern formation in developmental biology and microbial ecology, as well as provide a theoretical framework for the engineering of spatially-arranged cell systems.
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    Spatial biology of Ising-like synthetic genetic networks
    (2023) Simpson, Kevin; L'Homme Iriarte, Alfredo Juan; Keymer, Juan E.; Federici, Fernán
    Background: Understanding how spatial patterns of gene expression emerge from the interaction of individual gene networks is a fundamental challenge in biology. Developing a synthetic experimental system with a common theoretical framework that captures the emergence of short- and long-range spatial correlations (and anti-correlations) from interacting gene networks could serve to uncover generic scaling properties of these ubiquitous phenomena. Results: Here, we combine synthetic biology, statistical mechanics models, and computational simulations to study the spatial behavior of synthetic gene networks (SGNs) in Escherichia coli quasi-2D colonies growing on hard agar surfaces. Guided by the combined mechanisms of the contact process lattice simulation and two-dimensional Ising model (CPIM), we describe the spatial behavior of bi-stable and chemically coupled SGNs that self-organize into patterns of long-range correlations with power-law scaling or short-range anti-correlations. These patterns, resembling ferromagnetic and anti-ferromagnetic configurations of the Ising model near critical points, maintain their scaling properties upon changes in growth rate and cell shape. Conclusions: Our findings shed light on the spatial biology of coupled and bistable gene networks in growing cell populations. This emergent spatial behavior could provide insights into the study and engineering of self-organizing gene patterns in eukaryotic tissues and bacterial consortia.
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    The spatial ecology of microbes
    (2021) Wetherington, Miles T.; Keymer, Juan E.; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    Guided by cell biophysics experimentation and equipped with toolsets from theoretical ecology, the aim of my thesis is to explore the ways in which spatial structure influences the dynamics and distributions of microbial cells, populations and communities. In my first project, we highlighted range expansion experiments of a colicin producing-colicin sensitive E.coli community on solid agar; The process of colony formation is driven by colicin production, cell lysis and division all driving the dynamical structure and ecological composition of the colony. Making analogies to percolation theory from statistical physics, we were able to develop a spatial model to quantify regimes of strain coexistence, competitive exclusion and extinction. Next we aimed to understand the spatial conditions under which microbial common goods games could persist. A particular bacterial system motivating this study was Pseudomonas aeruginosa, which excretes a costly ‘iron-scavenging’ compound (siderophore) in order to bind and transport iron across the cell membrane. This compound represents a common-pool resource, susceptible to exploitation by nearby bacteria free from producing this metabolically costly resource. With this system in mind we asked the following question: what spatial conditions permit these common-pool resources to be monopolized by a cooperator strategy in competition with an exploiter strategy? By developing a stochastic spatial model, we quantified the phase transition from monopolized to exploited and predicted which circumstances to expect coexistence between niche constructing and exploiter strategies as a result of differences in niche monopolization and colonization rates, respectively, and when to expect a collapse of the niche and a ‘tragedy of the commons’. Following this work, I began to apply newly acquired expertise in microfluidics, microfabrication techniques, microscopy and experimental cell biophysics in order to observe and study the spatial colonization dynamics of E.coli and P.aeruginosa in structured microfabricated landscapes. We showed how these two bacterial species enact a competition-colonization tradeoff where the faster colonizing E.coli can be overwhelmed locally by the slower but superior competitor, P.aeruginosa. This work constituted the first evidence of an abstract ecological theory in a spatial bacterial community. Furthermore, these results showed the importance of spatial structure in leading to coexistence as E.coli is able to effectively localize P.aeruginosa populations when competing in a patchy landscape via priority-effects. Conversely, in well-mixed ‘mean-field’ conditions the superior competitor always wins. In order to address the priority effects observed by E.coli, we made analogies to the Kronig-Penny model of solid state physics to our patchy landscape. To help understand the role habitat structure plays in the process of ecological colonization via invading wave populations, we represented our patchy landscapes as a periodic potential. An interesting result of such interpretation is the opening for the possibility of Anderson localization phenomena to take place; whereby species modulate each other’s dynamic habitat landscape. In this scenario E. coli cells modulate the potential seen by P.aeruginosa and introduce randomness to ecological corridors. In this way E. coli can induce strong localization in the spatial distribution of the P.aeruginosa metapopulation. This work highlights the importance of invisible corridor interactions and their potential to determine patterns of patch occupancy. Building on these results we next made an explicit connection between the topological properties of spatially structured microbial landscapes and Taylor’s Law, which asserts that the fluctuations within a metapopulation is a power law function of the mean. This statistical phenomena of populations, while well-documented in both the macro- and microscopic world, has yet to be connected to processes shaping spatially structured microbial populations and communities. Pursuing this analogy from solid state physics further we generated different degrees of randomness in the patchconnecting ecological corridor widths within a microfabricated microfluidics landscape, we found that a critical level of randomness leads to a qualitative transition in the fluctuation scaling of an Escherichia coli metapopulation. That induced randomness leads to such a result is neither expected experimentally nor completely understood theoretically. Nevertheless, these results bring a landscape perspective to Taylor’s law and the desire to connect this phenomena to ecological processes. Furthermore, bridging Taylor’s Law with other ecological scaling laws is an ongoing effort in the field of macroecology and one which we think would benefit from collaborations between theoreticians and experimental cell biophysics techniques like the one implemented here. Finally, given the unique perspective of this collaborative effort between cell biophysics and theoretical ecology, we conclude this thesis with a review of the literature in the field. Primarily, we focus on the necessary theoretical ecology needed for cell biophysicists to interpret their experimental results. In particular, we review landmark experimental cell biophysics discoveries from the past 15 years ranging from single-cell, population and community/biofilm studies, as well as following-up with newer findings all of which we discuss from an ecological viewpoint.