Abstract: Generally applicable methods for using phenotypic probes to reduce or eliminate false positives, and thereby identify physiologically relevant endogenous target molecules, are provided. The methods use both protein interaction assay steps and phenotypic assay steps. In some embodiments, protein interactions are detected utilizing yeast two hybrid techniques.

Abstract: The present invention is directed to selection systems for the identification of cell proliferation genes based on functional analysis. More specifically, the invention is directed to a process for the identification of a cell proliferation promoting activity, the isolation of genes involved in such cell proliferation promoting activity, and the use of the so identified genes for the diagnosis or treatment of a disease associated with excessive cell proliferation. The invention further is directed to the design and development of antibodies, peptides, nucleic acids, and other compounds which specifically interfere with the function of the identified gene and/or its gene product, and pharmaceutical compositions comprising such compounds, for the treatment of diseases associated with inappropriate or unregulated cell proliferation.

Abstract: Methods for identifying nucleic acid sequences that affect a cellular phenotype are disclosed. The method uses a reporter gene whose level of expression correlates with the phenotype in conjunction with a method or device for measuring the level of reporter expression. An expression library is introduced into the cells, and those cells exhibiting changes in reporter expression level are selected. Expression library inserts from the selected cells are isolated, thereby providing a sub-library enriched for sequences that affect the phenotype reflected by the reporter. Further rounds of sub-library introduction and cell selection may be carried out to provide additional enrichment. Sequences identified using this method may be used to ascertain the identity of additional molecules involved in generating the cellular phenotype.

Abstract: Methods and compositions for peptides or protein fragments displayed on scaffolds and libraries of sequences encoding peptides or protein fragments displayed on scaffolds that permit the properties of the library to be easily and quantitatively monitored are disclosed. The scaffold is a protein that is capable of emitting light. Thus, analysis of the expression of individual members of the library when they are expressed in cells may be carried out using instruments that can analyze the emitted light, such as flow sorter (FACS), a spectrophotometer, a microtitre plate reader, a CCD, a fluorescence microscope, or other similar device. This permits screening of the expression library in host cells on a cell-by-cell basis, and enrichment of the library for sequences that have predetermined characteristics.

Abstract: The present invention is directed to selection systems for the identification of cell proliferation genes based on functional analysis. More specifically, the invention is directed to a process for the identification of a cell proliferation promoting activity, the isolation of genes involved in such cell proliferation promoting activity, and the use of the so identified genes for the diagnosis or treatment of a disease associated with excessive cell proliferation. The invention further is directed to the design and development of antibodies, peptides, nucleic acids, and other compounds which specifically interfere with the function of the identified gene and/or its gene product, and pharmaceutical compositions comprising such compounds, for the treatment of diseases associated with inappropriate or unregulated cell proliferation.

Abstract: Methods for identifying nucleic acid sequences that affect a cellular phenotype are disclosed. The method uses a reporter gene whose level of expression correlates with the phenotype in conjunction with a method or device for measuring the level of reporter expression. An expression library is introduced into the cells, and those cells exhibiting changes in reporter expression level are selected. Expression library inserts from the selected cells are isolated, thereby providing a sub-library enriched for sequences that affect the phenotype reflected by the reporter. Further rounds of sub-library introduction and cell selection may be carried out to provide additional enrichment Sequences identified using this method may be used to ascertain the identity of additional molecules involved in generating the cellular phenotype.