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Axelrod, Kevin

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Axelrod

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Axelrod, Kevin

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2015 - 20162

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    Phenotypic states become increasingly sensitive to perturbations near a bifurcation in a synthetic gene network
    (eLife Sciences Publications, Ltd, 2015) Axelrod, Kevin; Sanchez, Alvaro; Gore, Jeff
    Microorganisms often exhibit a history-dependent phenotypic response after exposure to a stimulus which can be imperative for proper function. However, cells frequently experience unexpected environmental perturbations that might induce phenotypic switching. How cells maintain phenotypic states in the face of environmental fluctuations remains an open question. Here, we use environmental perturbations to characterize the resilience of phenotypic states in a synthetic gene network near a critical transition. We find that far from the critical transition an environmental perturbation may induce little to no phenotypic switching, whereas close to the critical transition the same perturbation can cause many cells to switch phenotypic states. This loss of resilience was observed for perturbations that interact directly with the gene circuit as well as for a variety of generic perturbations-such as salt, ethanol, or temperature shocks-that alter the state of the cell more broadly. We obtain qualitatively similar findings in natural gene circuits, such as the yeast GAL network. Our findings illustrate how phenotypic memory can become destabilized by environmental variability near a critical transition. DOI: http://dx.doi.org/10.7554/eLife.07935.001
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    Bistable dynamics in microbial ecology and systems biology
    (2016-05-04) Axelrod, Kevin; Cohen, Adam E.; Klein, Allon M.; Springer, Michael; Hogle, James M.
    Bistability, in which a system has two stable states, is a common property of many dynamic systems. This thesis explores the properties of such systems across a range of length scales, from gene circuits to ecosystems. Cells often store memories of environmental stimuli using bistable gene circuits. High fidelity memory storage requires that a state has a long lifetime. However, an underappreciated aspect of stable memory is that the distance from a bifurcation could determine how sensitive a state is to perturbations in the extracellular environment. We predict that cell memory should become increasingly sensitive to perturbations near a bifurcation and test this idea in three different gene circuits: a toggle switch, the yeast galactose utilization network, and the E. coli lactose utilization network. In a second study, we explore how the environmental context in which two species interact can influence their mode of interaction. Two species in nature often form reciprocally beneficial partnerships termed mutualisms, but in certain environmental regimes the species might shift to competing with one another for resources. This mutualism-competition transition has been understudied in experimental ecosystems. Using a synthetic yeast cross-feeding mutualism, we modulate the degree to which two partners rely on each other by supplementing the cells with variable amounts of nutrients. Surprisingly, we find that as the amount of supplemented nutrients is increased, the system passes through eight qualitatively distinct dynamic regimes: extinction, obligatory mutualism, obligatory/facultative mutualism, facultative mutualism, parasitism, amensalism, competition, and competitive exclusion. In a third study, we probe how population growth dynamics can influence the probability of evolutionary rescue. Natural populations frequently face harsh environments in which their death rate exceeds their birth rate and population size tends toward zero. In such scenarios, populations can either go extinct, migrate to a better habitat, or adapt to the harsh environment. Natural populations often exhibit an “Allee effect,” in which populations grow slowly at low density due to struggles with such behaviors as finding a mate or collective hunting. We hypothesize that the presence of an Allee effect could impede evolutionary rescue and confirm this hypothesis in a model laboratory yeast ecosystem.