Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

The structure-function relationship of oncogenic LMTK3

Elucidating signaling driven by lemur tyrosine kinase 3 (LMTK3) could help drug development. Here, we solve the crystal structure of LMTK3 kinase domain to 2.1Å resolution, determine its consensus motif and phosphoproteome, unveiling in vitro and in vivo LMTK3 substrates. Via high-throughput homogeneous time-resolved fluorescence screen coupled with biochemical, cellular, and biophysical assays, we identify a potent LMTK3 small-molecule inhibitor (C28). Functional and mechanistic studies reveal LMTK3 is a heat shock protein 90 (HSP90) client protein, requiring HSP90 for folding and stability, while C28 promotes proteasome-mediated degradation of LMTK3. Pharmacologic inhibition of LMTK3 decreases proliferation of cancer cell lines in the NCI-60 panel, with a concomitant increase in apoptosis in breast cancer cells, recapitulating effects of LMTK3 gene silencing. Furthermore, LMTK3 inhibition reduces growth of xenograft and transgenic breast cancer mouse models without displaying systemic toxicity at effective doses. Our data reinforce LMTK3 as a druggable target for cancer therap

Calculating Evolutionary Dynamics in Structured Populations

Evolution is shaping the world around us. At the core of every evolutionary process is a population of reproducing individuals. The outcome of an evolutionary process depends on population structure. Here we provide a general formula for calculating evolutionary dynamics in a wide class of structured populations. This class includes the recently introduced “games in phenotype space” and “evolutionary set theory.” There can be local interactions for determining the relative fitness of individuals, but we require global updating, which means all individuals compete uniformly for reproduction. We study the competition of two strategies in the context of an evolutionary game and determine which strategy is favored in the limit of weak selection. We derive an intuitive formula for the structure coefficient, σ, and provide a method for efficient numerical calculation

Persistence Increases with Diversity and Connectance in Trophic Metacommunities

We are interested in understanding if metacommunity dynamics contribute to the persistence of complex spatial food webs subject to colonization-extinction dynamics. We study persistence as a measure of stability of communities within discrete patches, and ask how do species diversity, connectance, and topology influence it in spatially structured food webs.We answer this question first by identifying two general mechanisms linking topology of simple food web modules and persistence at the regional scale. We then assess the robustness of these mechanisms to more complex food webs with simulations based on randomly created and empirical webs found in the literature. We find that linkage proximity to primary producers and food web diversity generate a positive relationship between complexity and persistence in spatial food webs. The comparison between empirical and randomly created food webs reveal that the most important element for food web persistence under spatial colonization-extinction dynamics is the degree distribution: the number of prey species per consumer is more important than their identity.With a simple set of rules governing patch colonization and extinction, we have predicted that diversity and connectance promote persistence at the regional scale. The strength of our approach is that it reconciles the effect of complexity on stability at the local and the regional scale. Even if complex food webs are locally prone to extinction, we have shown their complexity could also promote their persistence through regional dynamics. The framework we presented here offers a novel and simple approach to understand the complexity of spatial food webs

Invasion success of a widespread invasive predator may be explained by a high predatory efficacy but may be influenced by pathogen infection

Invasive alien species (IAS) can drive community change through ecological interactions. Parasites and pathogens can play an important role in community function including mitigating or enhancing IAS impacts. Despite this, the degree to which pathogen pressure influences IAS impacts remains poorly understood. We quantified the predatory behaviour of the highly invasive alien harlequin ladybird (Harmonia axyridis) and two UK native species, the 7-spot (Coccinella septempunctata) and 2-spot (Adalia bipunctata) ladybirds, using comparative functional response experiments. We investigated the impacts of pathogen infection on the predatory ability of the ladybirds by exposing individuals to Beauveria bassiana, a widespread entomopathogen. Invasive H. axyridis was a more efficient predator than both the native A. bipunctata and C. septempunctata, often having higher attack and/or lower prey handling time coefficients, whereas native A. bipunctata were the least efficient predators. These differences were found in both adult and larval life-stages. Beauveria bassiana infection significantly altered the predatory efficiency of adult and larval ladybird predators. The effects of pathogenic infection differed between species and life-stage but in many cases infection resulted in a reduced predatory ability. We suggest that the interactions between IAS and pathogens are integral to determining invasion success and impact

Invasion success of a widespread invasive predator may be explained by a high predatory efficacy but may be influenced by pathogen infection

Invasive alien species (IAS) can drive community change through ecological interactions. Parasites and pathogens can play an important role in community function including mitigating or enhancing IAS impacts. Despite this, the degree to which pathogen pressure influences IAS impacts remains poorly understood. We quantified the predatory behaviour of the highly invasive alien harlequin ladybird (Harmonia axyridis) and two UK native species, the 7-spot (Coccinella septempunctata) and 2-spot (Adalia bipunctata) ladybirds, using comparative functional response experiments. We investigated the impacts of pathogen infection on the predatory ability of the ladybirds by exposing individuals to Beauveria bassiana, a widespread entomopathogen. Invasive H. axyridis was a more efficient predator than both the native A. bipunctata and C. septempunctata, often having higher attack and/or lower prey handling time coefficients, whereas native A. bipunctata were the least efficient predators. These differences were found in both adult and larval life-stages. Beauveria bassiana infection significantly altered the predatory efficiency of adult and larval ladybird predators. The effects of pathogenic infection differed between species and life-stage but in many cases infection resulted in a reduced predatory ability. We suggest that the interactions between IAS and pathogens are integral to determining invasion success and impact