7 research outputs found

    Programmed Allee Effect in Bacteria Causes a Tradeoff Between Population Spread and Survival

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    Dispersal is necessary for spread into new habitats, but it has also been shown to inhibit spread. Theoretical studies have suggested that the presence of a strong Allee effect may account for these counterintuitive observations. Experimental demonstration of this notion is lacking due to the difficulty in quantitative analysis of such phenomena in a natural setting. We engineered Escherichia coli to exhibit a strong Allee effect and examined how the Allee effect would affect the spread of the engineered bacteria. We showed that the Allee effect led to a biphasic dependence of bacterial spread on the dispersal rate: spread is promoted for intermediate dispersal rates but inhibited at low or high dispersal rates. The shape of this dependence is contingent upon the initial density of the source population. Moreover, the Allee effect led to a tradeoff between effectiveness of population spread and survival: increasing the number of target patches during dispersal allows more effective spread, but it simultaneously increases the risk of failing to invade or of going extinct. We also observed that total population growth is transiently maximized at an intermediate number of target patches. Finally, we demonstrate that fluctuations in cell growth may contribute to the paradoxical relationship between dispersal and spread. Our results provide direct experimental evidence that the Allee effect can explain the apparently paradoxical effects of dispersal on spread and have implications for guiding the spread of cooperative organisms

    Immunotherapy Gone Viral: Bortezomib and oHSV Enhance Antitumor NK-Cell Activity

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    A Synthetic Biology Approach to Understanding Cellular Information Processing

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    The survival of cells and organisms requires proper responses to environmental signals. These responses are governed by cellular networks, which serve to process diverse environmental cues. Biological networks often contain recurring network topologies called “motifs”. It has been recognized that the study of such motifs allows one to predict the response of a biological network and thus cellular behavior. However, studying a single motif in complete isolation of all other network motifs in a natural setting is difficult. Synthetic biology has emerged as a powerful approach to understanding the dynamic properties of network motifs. In addition to testing existing theoretical predictions, construction and analysis of synthetic gene circuits has led to the discovery of novel motif dynamics, such as how the combination of simple motifs can lead to autonomous dynamics or how noise in transcription and translation can affect the dynamics of a motif. Here, we review developments in synthetic biology as they pertain to increasing our understanding of cellular information processing. We highlight several types of dynamic behaviors that diverse motifs can generate, including the control of input/output responses, the generation of autonomous spatial and temporal dynamics, as well as the influence of noise in motif dynamics and cellular behavior

    The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

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    The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes
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