Rational Design

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The Experts below are selected from a list of 121974 Experts worldwide ranked by ideXlab platform

Pamela A Silver - One of the best experts on this subject based on the ideXlab platform.

  • Rational Design of evolutionarily stable microbial kill switches
    Molecular Cell, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, Samuel Okeefe, Elizabeth Redfield, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    Summary The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One useful but challenging situation is a switch between life and death depending on environment. Here are presented "essentializer" and "cryodeath" circuits, which act as kill switches in Escherichia coli . The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. Additionally, cryodeath was shown to control the growth environment of a population, with an escape frequency of less than 1 in 10 5 after 10 days of growth in the mammalian gut.

  • Rational Design of evolutionarily stable microbial kill switches
    bioRxiv, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One particularly useful but challenging situation is a switch between life and death depending on environment. Here are presented 9essentializer9 and 9cryodeath9 circuits, which act as kill switches in Escherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a novel toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. In addition, cryodeath was shown to control the growth environment of a bacterial population, with an escape rate of less than 1 in 105 after ten days in vivo.

  • Rational Design of memory in eukaryotic cells
    Genes & Development, 2007
    Co-Authors: Caroline M Ajofranklin, David A Drubin, Julian A Eskin, Elaine P S Gee, Dirk Landgraf, Ira Phillips, Pamela A Silver
    Abstract:

    The ability to logically engineer novel cellular functions promises a deeper understanding of biological systems. Here we demonstrate the Rational Design of cellular memory in yeast that employs autoregulatory transcriptional positive feedback. We built a set of transcriptional activators and quantitatively characterized their effects on gene expression in living cells. Modeling in conjunction with the quantitative characterization of the activator-promoter pairs accurately predicts the behavior of the memory network. This study demonstrates the power of taking advantage of components with measured quantitative parameters to specify eukaryotic regulatory networks with desired properties.

Finn Stirling - One of the best experts on this subject based on the ideXlab platform.

  • Rational Design of evolutionarily stable microbial kill switches
    Molecular Cell, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, Samuel Okeefe, Elizabeth Redfield, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    Summary The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One useful but challenging situation is a switch between life and death depending on environment. Here are presented "essentializer" and "cryodeath" circuits, which act as kill switches in Escherichia coli . The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. Additionally, cryodeath was shown to control the growth environment of a population, with an escape frequency of less than 1 in 10 5 after 10 days of growth in the mammalian gut.

  • Rational Design of evolutionarily stable microbial kill switches
    bioRxiv, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One particularly useful but challenging situation is a switch between life and death depending on environment. Here are presented 9essentializer9 and 9cryodeath9 circuits, which act as kill switches in Escherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a novel toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. In addition, cryodeath was shown to control the growth environment of a bacterial population, with an escape rate of less than 1 in 105 after ten days in vivo.

Jeffrey C Way - One of the best experts on this subject based on the ideXlab platform.

  • Rational Design of evolutionarily stable microbial kill switches
    Molecular Cell, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, Samuel Okeefe, Elizabeth Redfield, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    Summary The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One useful but challenging situation is a switch between life and death depending on environment. Here are presented "essentializer" and "cryodeath" circuits, which act as kill switches in Escherichia coli . The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. Additionally, cryodeath was shown to control the growth environment of a population, with an escape frequency of less than 1 in 10 5 after 10 days of growth in the mammalian gut.

  • Rational Design of evolutionarily stable microbial kill switches
    bioRxiv, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One particularly useful but challenging situation is a switch between life and death depending on environment. Here are presented 9essentializer9 and 9cryodeath9 circuits, which act as kill switches in Escherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a novel toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. In addition, cryodeath was shown to control the growth environment of a bacterial population, with an escape rate of less than 1 in 105 after ten days in vivo.

J Oliver - One of the best experts on this subject based on the ideXlab platform.

  • Rational Design of evolutionarily stable microbial kill switches
    Molecular Cell, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, Samuel Okeefe, Elizabeth Redfield, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    Summary The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One useful but challenging situation is a switch between life and death depending on environment. Here are presented "essentializer" and "cryodeath" circuits, which act as kill switches in Escherichia coli . The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. Additionally, cryodeath was shown to control the growth environment of a population, with an escape frequency of less than 1 in 10 5 after 10 days of growth in the mammalian gut.

  • Rational Design of evolutionarily stable microbial kill switches
    bioRxiv, 2017
    Co-Authors: Finn Stirling, Lisa Bitzan, J Oliver, Jeffrey C Way, Pamela A Silver
    Abstract:

    The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One particularly useful but challenging situation is a switch between life and death depending on environment. Here are presented 9essentializer9 and 9cryodeath9 circuits, which act as kill switches in Escherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ Rational Design and a novel toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable. Both kill switches were shown to maintain functionality in vitro for at least 140 generations. In addition, cryodeath was shown to control the growth environment of a bacterial population, with an escape rate of less than 1 in 105 after ten days in vivo.

Kristin A Persson - One of the best experts on this subject based on the ideXlab platform.

  • Elucidating Solvation Structures for Rational Design of Multivalent Electrolytes—A Review
    Topics in Current Chemistry, 2018
    Co-Authors: Nav Nidhi Rajput, Trevor J Seguin, Xiaohui Qu, Brandon M Wood, Kristin A Persson
    Abstract:

    Fundamental molecular-level understanding of functional properties of liquid solutions provides an important basis for Designing optimized electrolytes for numerous applications. In particular, exhaustive knowledge of solvation structure, stability, and transport properties is critical for developing stable electrolytes for fast-charging and high-energy-density next-generation energy storage systems. Accordingly, there is growing interest in the Rational Design of electrolytes for beyond lithium-ion systems by tuning the molecular-level interactions of solvate species present in the electrolytes. Here we present a review of the solvation structure of multivalent electrolytes and its impact on the electrochemical performance of these batteries. A direct correlation between solvate species present in the solution and macroscopic properties of electrolytes is sparse for multivalent electrolytes and contradictory results have been reported in the literature. This review aims to illustrate the current understanding, compare results, and highlight future needs and directions to enable the deep understanding needed for the Rational Design of improved multivalent electrolytes.

  • Elucidating Solvation Structures for Rational Design of Multivalent Electrolytes-A Review.
    Topics in Current Chemistry, 2018
    Co-Authors: Nav Nidhi Rajput, Trevor J Seguin, Brandon M Wood, Kristin A Persson
    Abstract:

    Fundamental molecular-level understanding of functional properties of liquid solutions provides an important basis for Designing optimized electrolytes for numerous applications. In particular, exhaustive knowledge of solvation structure, stability, and transport properties is critical for developing stable electrolytes for fast-charging and high-energy-density next-generation energy storage systems. Accordingly, there is growing interest in the Rational Design of electrolytes for beyond lithium-ion systems by tuning the molecular-level interactions of solvate species present in the electrolytes. Here we present a review of the solvation structure of multivalent electrolytes and its impact on the electrochemical performance of these batteries. A direct correlation between solvate species present in the solution and macroscopic properties of electrolytes is sparse for multivalent electrolytes and contradictory results have been reported in the literature. This review aims to illustrate the current understanding, compare results, and highlight future needs and directions to enable the deep understanding needed for the Rational Design of improved multivalent electrolytes.