Eric D. Kelsic

Comparing Community Structure to Characteristics in Online Collegiate Social Networks

We study the structure of social networks of students by examining the graphs of Facebook “friendships” at five U.S. universities at a single point in time. We investigate the community structure of each single-institution network and employ visual and quantitative tools, including standardized pair-counting methods, to measure the correlations between the network communities and a set of self-identified user characteristics (residence, class year, major, and high school). We review the basic properties and statistics of the employed pair-counting indices and recall, in simplified notation, a useful formula for the

Counteraction of antibiotic production and degradation stabilizes microbial communities

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Spatiotemporal microbial evolution on antibiotic landscapes

-score of the Rand coefficient. Our study illustrates how to examine different instances of social networks constructed in similar environments, emphasizes the array of social forces that combine to form “communities,” and leads to comparative observations about online social structures, which reflect offline social structures. We calculate the relative contributions of different characteristics to the community structure of individual universities and compare these relative contributions at different universities. For example, we examine the importance of common high school affiliation at large state universities and the varying degrees of influence that common major can have on the social structure at different universities. The heterogeneity of the communities that we observe indicates that university networks typically have multiple organizing factors rather than a single dominant one.

High-order species interactions shape ecosystem diversity.

A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity, and in particular how antibiotic-producing, -sensitive and -resistant species coexist. While cyclic ‘rock–paper–scissors’ interactions can stabilize communities in spatial environments, coexistence in unstructured environments remains unexplained. Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on three-way interactions in which an antibiotic-degrading species attenuates the inhibitory interactions between two other species. These interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by ‘cheating’ species that cease to produce or degrade antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamic behaviours ranging from stable fixed points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatially structured and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity.

High-throughput creation and functional profiling of DNA sequence variant libraries using CRISPR–Cas9 in yeast

A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)–plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front. While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front, we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behind more sensitive lineages. The MEGA-plate provides a versatile platform for studying microbial adaption and directly visualizing evolutionary dynamics.

High-throughput creation and functional profiling of eukaryotic DNA sequence variant libraries using CRISPR/Cas9

Classical theory shows that large communities are destabilized by random interactions among species pairs, creating an upper bound on ecosystem diversity. However, species interactions often occur in high-order combinations, whereby the interaction between two species is modulated by one or more other species. Here, by simulating the dynamics of communities with random interactions, we find that the classical relationship between diversity and stability is inverted for high-order interactions. More specifically, while a community becomes more sensitive to pairwise interactions as its number of species increases, its sensitivity to three-way interactions remains unchanged, and its sensitivity to four-way interactions actually decreases. Therefore, while pairwise interactions lead to sensitivity to the addition of species, four-way interactions lead to sensitivity to species removal, and their combination creates both a lower and an upper bound on the number of species. These findings highlight the importance of high-order species interactions in determining the diversity of natural ecosystems.

Evolutionary stability of microbial communities with antibiotic degrading species

Construction and characterization of large genetic variant libraries is essential for understanding genome function, but remains challenging. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions, and insertions) with an efficiency of 80–100% in yeast, along with methods for tracking their fitness en masse. We demonstrate the utility of our approach by characterizing the DNA helicase SGS1 with small tiling deletion mutants that span the length of the protein and a series of point mutations against highly conserved residues in the protein. In addition, we created a genome-wide library targeting 315 poorly characterized small open reading frames (smORFs, <100 amino acids in length) scattered throughout the yeast genome, and assessed which are vital for growth under various environmental conditions. Our strategy allows fundamental biological questions to be investigated in a high-throughput manner with precision.

Community Structure in Online Collegiate Social Networks

Construction of genetic variant libraries with phenotypic measurement is central to advancing today’s functional genomics, and remains a grand challenge. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions and insertions), along with methods for tracking their fitness en masse. We demonstrate the utility of our approach in performing focused analysis of hundreds of mutants of a single protein and in investigating the biological function of an entire family of poorly characterized genetic elements. Our platform allows fundamental biology questions to be investigated in a quick, easy and affordable manner.

RNA Structural Determinants of Optimal Codons Revealed by MAGE-Seq

A major puzzle in ecology is how antibiotic resistant, sensitive and producer species coexist in close proximity. Recently, we showed that antibiotic degrading species dramatically alter community dynamics: replacing intrinsic resistance with resistance through degradation generates stable communities resilient to spatial mixing, large species abundance perturbations, changes in interaction strengths, and differences in species growth rates1. In addition to ecological stability, it is interesting to consider evolutionary stability of these communities to the appearance of cheater species that either cease production or degradation of antibiotics. Our investigation of evolutionary stability of cyclical 3-species communities revealed that these communities are robust to cheaters that stop degrading antibiotics. Our simulations also showed that cheaters that stop producing antibiotics do not take over the community1, yet they can transiently invade and cause community collapse2. In the analytical approximation we initially investigated, production cheaters with a small fitness advantage can invade the community simply because the benefit of inhibiting competitors is shared among all cells2. Here, we consider evolutionary stability to cheaters in our complete model1, where spatial mixing is introduced only after a short range colonization step. In this regime, an antibiotic producer cell directly benefits from killing nearby competitor species as it has a greater chance of colonizing the newly voided spaces created by the action of its antibiotic. Simulating response to cheater invasions for the cyclical three species community and for random 4-species ecologically stable topologies, we find that these communities can be fully resilient to both degradation and production cheaters. The strength of selection against cheaters varies with the area of the zone of inhibition around producers and is maximized for weak inhibition, where there is less overlap between the killing zones of neighboring cells. These results may aid the construction of complex synthetic communities that are both ecological and evolutionary stable.