Abstract: The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.

Abstract: The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.

Abstract: The invention provides methods and compositions for assaying hypoxia-inducible factor (HIF) prolyl hydroxylation. Subject assays may be cell-based or in vitro, and comprise incubating a mixture comprising an isolated or recombinantly expressed HIF-specific prolyl hydroxylase (HPH), and a substrate of the hydroxylase, under conditions whereby the hydroxylase prolyl hydroxylates the substrate, and detecting a resultant prolyl hydroxylation of the substrate. The mixture may also comprise a candidate agent which modulates the resultant prolyl hydroxylation. In particular embodiments, the hydroxylase is selected from the group consisting of human HPH1, HPH2 and HPH3, and/or the substrate comprises LAPY, wherein P is hydroxylated by the hydroxylase.

Abstract: The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.

Abstract: The invention provides methods and compositions relating to a novel kinase designated PAS Kinase (PASK). The compositions include isolated polypeptides comprising a native PASK protein or a PASK N-terminal domain and polypeptides consisting of a PASK PAS-A or PAS-B domain, as well as isolated polynucleotides encoding such polypeptides, and expression vectors and cells comprising such polynucleotides. The methods include binding assays comprising the steps of incubating a mixture comprising a subject polypeptide with a ligand under conditions wherein the polypeptide binds the ligand; and detecting binding of the polypeptide to the ligand.

Abstract: The invention provides methods and compositions relating to a novel kinase designated PAS Kinase (PASK). The compositions include isolated polypeptides comprising a native PASK protein or a PASK N-terminal domain and polypeptides consisting of a PASK PAS-A or PAS-B domain, as well as isolated polynucleotides encoding such polypeptides, and expression vectors and cells comprising such polynucleotides. The methods include binding assays comprising the steps of incubating a mixture comprising a subject polypeptide with a ligand under conditions wherein the polypeptide binds the ligand; and detecting binding of the polypeptide to the ligand.

Abstract: The invention provides methods and compositions relating to neuronal PAS domain proteins (NPAS) and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed NPAS encoding nucleic acids or purified from human cells. The invention provides isolated NPAS hybridization probes and primers capable of specifically hybridizing with the disclosed NPAS gene, NPAS-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Abstract: The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by an interleukin 4 signal transducer and activator of transcription, IL-4 Stat. IL-4 Stat peptides and IL-4 receptor peptides and nucleic acids encoding such peptides find therapeutic uses. The subject compositions include IL-4 Stat and IL-4 receptor proteins, portions thereof, nucleic acids encoding them, and specific antibodies. The disclosed pharmaceutical screening methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Abstract: The invention provides methods and compositions relating to endothelial PAS domain protein 1 (EPAS1) and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed EPAS1 encoding nucleic acids or purified from human cells. The invention provides isolated EPAS1 hybridization probes and primers capable of specifically hybridizing with the disclosed EPAS1 gene, EPAS1-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Abstract: The present invention relates to a method of specifically inhibiting the growth of a virus, particularly an animal virus, in a permissive host cell comprising introducing into the host cell a virus-related gene encoding a product capable of interacting with the genome of the infecting virus (or a product encoded therein) in a manner such that the life cycle of the infecting virus is disrupted. The invention also relates to a method of rendering a cell, particularly an animal cell, resistant to viral infection, and to a viral resistant cell.

Abstract: The invention provides methods and compositions relating to interleukin 2 signal transducers, particularly an isolated human signal transducer and activator of transcription 5 (hStat 5), or a fragment thereof having an hStat 5-specific binding affinity, nucleic acids encoding hStat 5, which nucleic acids may be part of hStat 5-expression vectors and may be incorporated into a recombinant cell, agents which selectively bind hStat 5 or hStat 5 intracellular binding targets, or disrupt the binding of hStat 5 to such intracellular targets, methods of making such agents and hStat 5-specific binding targets in the form of cell surface proteins and nucleic acids. An hStat 5 drug screening assay involves forming mixtures of an hStat 5, an intracellular hStat 5 binding target, and a prospective agent at different concentrations. The mixtures are incubated to permit the binding of the intracellular hStat 5 binding target to the hStat 5 and the mixtures are then analyzed for the presence of such binding.

Abstract: The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by an interleukin 4 signal transducer and activator of transcription, IL-4 Stat. IL-4 Stat peptides and IL-4 receptor peptides and nucleic acids encoding such peptides find therapeutic uses. The subject compositions include IL-4 Stat and IL-4 receptor proteins, portions thereof, nucleic acids encoding them, and specific antibodies. The disclosed pharmaceutical screening methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.