Publications by authors named "Adin Ross-Gillespie"

Article Synopsis
  • Therapeutic proteins, such as monoclonal antibodies, traditionally require the development of stable host cell lines, which is a time-consuming process that can delay new treatments.
  • During the COVID-19 pandemic, a new approach using the Leap-In Transposase® system allowed for the rapid creation of stable pools for manufacturing an anti-SARS-CoV-2 monoclonal antibody.
  • This expedited process enabled the production of clinical trial material in just 4.5 months, significantly faster than the usual 12-14 month timeline, while ensuring that product quality met all necessary specifications.
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How unicellular organisms optimize the production of compounds is a fundamental biological question. While it is typically thought that production is optimized at the individual-cell level, secreted compounds could also allow for optimization at the group level, leading to a division of labor where a subset of cells produces and shares the compound with everyone. Using mathematical modeling, we show that the evolution of such division of labor depends on the cost function of compound production.

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Given the rise of bacterial resistance against antibiotics, we urgently need alternative strategies to fight infections. Some propose we should disarm rather than kill bacteria, through targeted disruption of their virulence factors. It is assumed that this approach (i) induces weak selection for resistance because it should only minimally impact bacterial fitness, and (ii) is specific, only interfering with the virulence factor in question.

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Bacterial traits that contribute to disease are termed "virulence factors" and there is much interest in therapeutic approaches that disrupt such traits. What remains less clear is whether a virulence factor identified as such in a particular context is also important in infections involving different host and pathogen types. Here, we address this question using a meta-analytic approach.

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Microbes are intensely social organisms that routinely cooperate and coordinate their activities to express elaborate population level phenotypes. Such coordination requires a process of collective decision-making, in which individuals detect and collate information not only from their physical environment, but also from their social environment, in order to arrive at an appropriately calibrated response. Here, we present a conceptual overview of collective decision-making as it applies to all group-living organisms; we introduce key concepts and principles developed in the context of animal and human group decisions; and we discuss, with appropriate examples, the applicability of each of these concepts in microbial contexts.

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Background And Objectives: Conventional antibiotics select strongly for resistance and are consequently losing efficacy worldwide. Extracellular quenching of shared virulence factors could represent a more promising strategy because (i) it reduces the available routes to resistance (as extracellular action precludes any mutations blocking a drug's entry into cells or hastening its exit) and (ii) it weakens selection for resistance, as fitness benefits to emergent mutants are diluted across all cells in a cooperative collective. Here, we tested this hypothesis empirically.

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Over the past decade, there has been enormous interest in understanding the great diversity of microbial cooperative behaviors, including communication, group-based swarming, fruiting-body formation, and the secretion of group-beneficial enzymes and food-scavenging molecules. Zhang and Rainey, henceforth Z&R, recently contended that sociomicrobiologists have been overzealous in their casting of microbes as inherently social organisms, and too hasty in interpreting microbial behaviors in a social evolutionary framework. This challenge accompanied a set of experiments in which they revisited one of the best-studied social behaviors in bacteria-the production of diffusible, sharable iron-scavenging siderophore molecules.

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Bacteria often possess multiple siderophore-based iron uptake systems for scavenging this vital resource from their environment. However, some siderophores seem redundant, because they have limited iron-binding efficiency and are seldom expressed under iron limitation. Here, we investigate the conundrum of why selection does not eliminate this apparent redundancy.

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The results of numerous economic games suggest that humans behave more cooperatively than would be expected if they were maximizing selfish interests. It has been argued that this is because individuals gain satisfaction from the success of others, and that such prosocial preferences require a novel evolutionary explanation. However, in previous games, imperfect behavior would automatically lead to an increase in cooperation, making it impossible to decouple any form of mistake or error from prosocial cooperative decisions.

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Although cooperative systems can persist in nature despite the potential for exploitation by noncooperators, it is often observed that small changes in population demography can tip the balance of selective forces for or against cooperation. Here we consider the role of population density in the context of microbial cooperation. First, we account for conflicting results from recent studies by demonstrating theoretically that: (1) for public goods cooperation, higher densities are relatively unfavorable for cooperation; (2) in contrast, for self-restraint-type cooperation, higher densities can be either favorable or unfavorable for cooperation, depending on the details of the system.

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The ability of pathogenic bacteria to exploit their hosts depends upon various virulence factors, released in response to the concentration of small autoinducer molecules that are also released by the bacteria [1-5]. In vitro experiments suggest that autoinducer molecules are signals used to coordinate cooperative behaviors and that this process of quorum sensing (QS) can be exploited by individual cells that avoid the cost of either producing or responding to signal [6, 7]. However, whether QS is an exploitable social trait in vivo, and the implications for the evolution of virulence [5, 8-10], remains untested.

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Hamilton's inclusive fitness theory provides a leading explanation for the problem of cooperation. A general result from inclusive fitness theory is that, except under restrictive conditions, cooperation should not be subject to frequency-dependent selection. However, several recent studies in microbial systems have demonstrated that the relative fitness of cheaters, which do not cooperate, is greater when cheaters are rarer.

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Inbreeding is typically detrimental to fitness. However, some animal populations are reported to inbreed without incurring inbreeding depression, ostensibly due to past "purging" of deleterious alleles. Challenging this is the position that purging can, at best, only adapt a population to a particular environment; novel selective regimes will always uncover additional inbreeding load.

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