Abstract: The present application relates to nucleic acids that encode an miRNA and a sensor domain that can respond to a ligand. In some embodiments, the sensor domain is an RNA aptamer that modulates processing of the miRNA by an RNA processing enzyme, for example, Drosha.

Abstract: The present invention relates to host cells that produce compounds that are characterized as benzylisoquinolines, as well as select precursors and intermediates thereof. The host cells comprise one, two or more heterologous coding sequences wherein each of the heterologous coding sequences encodes an enzyme involved in the metabolic pathway of a benzylisoquinoline, or its precursors or intermediates from a starting compound. The invention also relates to methods of producing the benzylisoquinoline, as well as select precursors and intermediates thereof by culturing the host cells under culture conditions that promote expression of the enzymes that produce the benzylisoquinoline or precursors or intermediates thereof.

Abstract: The invention provides an improved design for the construction of extensible nucleic acid-based, ligand-controlled regulatory systems, and the nucleic acid regulatory systems resulting therefrom. The invention contemplates improving the design of the switches (ligand-controlled regulatory systems) through the design of an information transmission domain (ITD). The improved ITD eliminates free-floating ends of the switching and the competing strands, and localizes competitive hybridization events to a contiguous strand of competing and switching strands in a strand-displacement mechanism-based switch, thereby improving the kinetics of strand-displacement. The improved regulatory systems have many uses in various biological systems, including gene expression control or ligand-concentration sensing.

Abstract: The invention relates to aptamer-regulated, ligand-responsive nucleic acids, or “ampliSwitches,” and uses thereof. Particular embodiments include a ligand-responsive nucleic acid that comprises a primer sequence domain and an aptamer domain that is responsive to a ligand.

Abstract: The invention provides various signal processing devices for integrating two or more biological signals (e.g., the presence, absence or concentration of specific ligands, etc.) to generate a status output, or a response that modulates one or more biological activities based on the status of the biological signals. The various described signal processing/integration mechanisms may be combined with one another to provide the device with more flexibility in integrating high-order cellular information. The signal processing devices of the invention have many uses in various biological systems, including gene expression control or ligand-concentration sensing.

Abstract: Aspects of the invention include host cells that are engineered to produce benzylisoquinoline alkaloids (BIAs). The host cells include heterologous coding sequences for a variety of enzymes involved in synthetic pathways from starting compounds to BIAs of the host cell. Also provided are methods of producing the BIAs of interest by culturing the host cells under culture conditions that promote expression of enzymes encoded by the heterologous coding sequences of the host cells. Aspects of the invention further include compositions, e.g., host cells, starting compounds and kits, etc., that find use in methods of the invention.

Abstract: The invention relates to aptamer-regulated, ligand-responsive nucleic acids, or “ampliSwitches,” and uses thereof. Particular embodiments include a ligand-responsive nucleic acid that comprises a primer sequence domain and an aptamer domain that is responsive to a ligand.

Abstract: An extensible RNA-based framework for engineering ligand-controlled gene regulatory systems, called ribozyme switches, that exhibit tunable regulation, design modularity, and target specificity is provided. These switch platforms typically contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. A variety of modes of standardized information transmission between these domains can be employed, and this application demonstrates a mechanism that allows for the reliable and modular assembly of functioning synthetic hammerhead ribozyme switches and regulation of ribozyme activity in response to various effectors. In some embodiments aptamer-regulated cis-acting hammerhead ribozymes are provided.

Abstract: The invention described herein relates to an RNA-based control device that senses the presence and/or concentration of at least one protein ligand, preferably through its protein-binding aptamer domain, and regulates a target gene expression through alternative splicing of the target gene in which the RNA-based control device is integrated. The device has uses in therapeutic as well as diagnostic applications.

Abstract: The invention provides an improved design for the construction of extensible nucleic acid-based, ligand-controlled regulatory systems, and the nucleic acid regulatory systems resulting therefrom. The invention contemplates improving the design of the switches (ligand-controlled regulatory systems) through the design of an information transmission domain (ITD). The improved ITD eliminates free-floating ends of the switching and the competing strands, and localizes competitive hybridization events to a contiguous strand of competing and switching strands in a strand-displacement mechanism-based switch, thereby improving the kinetics of strand-displacement. The improved regulatory systems have many uses in various biological systems, including gene expression control or ligand-concentration sensing.

Abstract: The invention provides an improved design for the construction of extensible nucleic acid-based, ligand-controlled regulatory systems, and the nucleic acid regulatory systems resulting therefrom. The invention contemplates improving the design of the switches (ligand-controlled regulatory systems) through the design of an information transmission domain (ITD). The improved ITD eliminates free-floating ends of the switching and the competing strands, and localizes competitive hybridization events to a contiguous strand of competing and switching strands in a strand-displacement mechanism-based switch, thereby improving the kinetics of strand-displacement. The improved regulatory systems have many uses in various biological systems, including gene expression control or ligand-concentration sensing.

Abstract: The present application relates to nucleic acids that encode a RNA switch responsive to a ligand that can control the expression of a gene product that affects the cell fate determination of a mammalian cell are provided. In some embodiments, the system can be used to control the proliferation or activation of mammalian cells in response to a ligand that can be provided exogenously to the mammalian cell or can be produced by the mammalian cell. The system can be used to promote the growth or proliferation of human T cells in response to an exogenous ligand applied to the cells. In one embodiment, the system detects the ligand through a RNA aptamer that modulates expression of a gene product through activation or inactivation of a ribozyme that modulates expression of the gene product.

Abstract: The present application provides engineered yeast cells and uses thereof. In specific embodiments, the yeast cells have a mutation in the GAL2 gene. In specific embodiments, the yeast cells can be used for producing a protein or compound of interest.

Abstract: An extensible RNA-based framework for engineering ligand-controlled gene regulatory systems, called ribozyme switches, that exhibit tunable regulation, design modularity, and target specificity is provided. These switch platforms typically contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. A variety of modes of standardized information transmission between these domains can be employed, and this application demonstrates a mechanism that allows for the reliable and modular assembly of functioning synthetic hammerhead ribozyme switches and regulation of ribozyme activity in response to various effectors. In some embodiments aptamer-regulated cis-acting hammerhead ribozymes are provided.

Abstract: Methods of evaluating a gene-regulatory element, including libraries of known or candidate gene-regulatory elements, are provided. Aspects of the methods include cytometrically analyzing a cell comprising a gene-regulatory element construct, e.g., a plasmid, having an activity reporter comprising a first signal reporter domain which produces a first signal operatively coupled to a gene-regulatory element of interest; and a noise reporter comprising a second signal reporter which produces a second signal that is distinguishable from the first signal to obtain the first and second signals. The first signal is then normalized with the second signal to obtain a normalized activity signal, which normalized activity signal is then employed to evaluate the gene-regulatory element. Also provided are reagents, systems and kits that find use in practicing methods of the invention.

Abstract: The invention provides an improved design for the construction of extensible nucleic acid-based, ligand-controlled regulatory systems, and the nucleic acid regulatory systems resulting therefrom. The invention contemplates improving the design of the switches (ligand-controlled regulatory systems) through the design of an information transmission domain (ITD). The improved ITD eliminates free-floating ends of the switching and the competing strands, and localizes competitive hybridization events to a contiguous strand of competing and switching strands in a strand-displacement mechanism-based switch, thereby improving the kinetics of strand-displacement. The improved regulatory systems have many uses in various biological systems, including gene expression control or ligand-concentration sensing.

Abstract: An extensible RNA-based framework for engineering ligand-controlled gene regulatory systems, called ribozyme switches, that exhibit tunable regulation, design modularity, and target specificity is provided. These switch platforms typically contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. A variety of modes of standardized information transmission between these domains can be employed, and this application demonstrates a mechanism that allows for the reliable and modular assembly of functioning synthetic hammerhead ribozyme switches and regulation of ribozyme activity in response to various effectors. In some embodiments aptamer-regulated cis-acting hammerhead ribozymes are provided.

Abstract: The invention relates to aptamer-regulated, ligand-responsive nucleic acids, or “ampliSwitches,” and uses thereof. Particular embodiments include a ligand-responsive nucleic acid that comprises a primer sequence domain and an aptamer domain that is responsive to a ligand.

Abstract: The invention described herein relates to an RNA-based control device that senses the presence and/or concentration of at least one protein ligand, preferably through its protein-binding aptamer domain, and regulates a target gene expression through alternative splicing of the target gene in which the RNA-based control device is integrated. The device has uses in therapeutic as well as diagnostic applications.

Abstract: An extensible RNA-based framework for engineering ligand-controlled gene regulatory systems, called ribozyme switches, that exhibit tunable regulation, design modularity, and target specificity is provided. These switch platforms typically contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. A variety of modes of standardized information transmission between these domains can be employed, and this application demonstrates a mechanism that allows for the reliable and modular assembly of functioning synthetic hammerhead ribozyme switches and regulation of ribozyme activity in response to various effectors. In some embodiments aptamer-regulated cis-acting hammerhead ribozymes are provided.