Abstract: An sortase-mediated intercellular labeling method allowing for tracking ligand-receptor interaction both in vitro and in vivo; and uses thereof for tracking molecule interactions both in vitro and in vivo, identifying modulators of ligand-receptor interaction, identifying potential binding partners of a protein of interest, identifying B cells expressing high affinity B cell receptors to antigens, and identifying the antigen to which a T cell of interest binds.

Abstract: In some aspects, described herein is a DNA methylation reporter. In some aspects, the DNA methylation reporter comprises a promoter whose activity can be affected by exogenous methylation changes without being independently regulated by the DNA methylation machinery, operably linked to a DNA sequence that encodes a reporter molecule. In some embodiments the DNA methylation reporter comprises (i) a promoter derived from a mammalian imprinted gene promoter; and (ii) a sequence that encodes a reporter molecule that is detectable in individual mammalian cells, wherein the promoter is operably linked to the sequence that encodes the reporter molecule. Also described are nucleic acids that comprise the DNA methylation reporter, cells that have the DNA methylation reporter integrated into their genome, and non-human mammals comprising cells that have the DNA methylation reporter integrated into their genome.

Abstract: The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.

Abstract: The present invention provides compounds pounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.

Abstract: The present invention provides novel compounds (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrate, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits comprising the inventive Compounds, or compositions thereof, for treating and/or preventing a fungal or protozoan infection, inhibiting the activity of a fungal or protozoan enzyme, killing a fungus or protozoan, or inhibiting the growth of a fungus or protozoan. The fungus may be a Candida species, Sacchawmyces species, or other pathogenic fungal species. The compounds of the invention may inhibit the activity of fungal or protozoan mitochondrial phosphate carrier protein.

Abstract: Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.

Abstract: Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.

Abstract: Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human amyloid beta protein. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress amyloid beta-induced toxicity and genetic suppressors or enhancers of amyloid beta-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease.

Abstract: Disclosed are yeast expression constructs encoding a polypeptide containing a signal sequence, a Golgi-directing pro sequence, and a human amyloid beta protein, and mammalian expression constructs encoding a polypeptide containing a selected signal sequence and a human amyloid beta protein. Also disclosed are methods of screening cells to identify compounds that prevent or suppress amyloid beta-induced toxicity and genetic suppressors or enhancers of amyloid beta-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease.

Abstract: Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis.

Abstract: The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and pharmaceutical compositions thereof. The present invention also provides methods and kits using the inventive compounds and pharmaceutical compositions for treating and/or preventing diseases associated with protein aggregation, such as amyloidoses (e.g., Parkinson's disease and Alzheimer's disease), treating and/or preventing neurodegenerative diseases, treating and/or preventing diseases associated with Tar DNA binding protein 43 kDa, reducing or preventing protein aggregation, and/or modulating E3 ubiquitin ligase in a subject in need thereof.

Abstract: The present invention provides methods of identifying modulators of mTORC1 based upon their effect on GATOR2-Sestrin binding or Sestrin-leucine binding; and the use of such modulators to alter mTORC1 activity in a cell and to treat disease and conditions that are effected by mTORC1 activity.

Abstract: The presently disclosed subject matter provides hydrogel precursor compositions (e.g., solutions) for forming three-dimensional hydrogels that support growth of physiologically relevant tissue when at least one cell is cultured in the three-dimensional hydrogel, kits comprising the hydrogel precursor composition, three-dimensional hydrogels, methods of forming the three-dimensional hydrogels, methods of growing the physiologically relevant tissue using the three-dimensional hydrogels, physiologically relevant tissue grown in the three-dimensional hydrogels, methods of producing hormone-responsive tissue (e.g., milk-producing mammary tissue and related methods of producing milk), methods of screening for candidate agents useful for modulating hormonal responses (e.g., modulating milk production), method of screening for candidate therapeutic agents using the physiologically relevant tissue grown in the three-dimensional hydrogels (e.g., personalized cancer treatments), and related methods of treatment (e.g.

Abstract: In some aspects, polypeptides comprising single domain antibodies and methods of identifying single domain antibodies are provided. In some embodiments polypeptides comprising a single domain antibody and a sortase recognition sequence, are provided. In some aspects, products and methods of use in modulating the immune system, e.g., modulating an immune response, are provided.

Abstract: In some aspects, the invention provides methods of identifying, detecting, and/or measuring protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein activity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some aspects, the invention provides methods for identifying and/or characterizing compounds and/or for assessing compound specificity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some embodiments, a client protein is a kinase. In some embodiments, a compound is a kinase inhibitor. In some aspects, the invention provides methods of profiling kinase inhibitor specificity.

Abstract: The present invention provides novel compounds (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits comprising the inventive compounds, or compositions thereof, for treating and/or preventing a fungal or protozoan infection, inhibiting the activity of a fungal or protozoan enzyme, killing a fungus or protozoon, or inhibiting the growth of a fungus or protozoon. The fungus may be a Candida species, Aspergillus species, or other pathogenic fungal species. The compounds of the invention may inhibit the activity of fungal or protozoan cytochrome b and/or fungal or protozoan Hsp90. The present invention also provides synthetic methods of the inventive compounds.

Abstract: Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis.

Abstract: The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.

Abstract: The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.

Abstract: In some aspects, the invention relates to Heat Shock Protein-1 (HSF1) gene and HSF1 gene products. In some aspects, the invention provides methods of tumor diagnosis, prognosis, treatment-specific prediction, or treatment selection, the methods comprising assessing the level of HSF1 expression or HSF1 activation in a sample obtained from the tumor. In some aspects, the invention relates to the discovery that increased HSF1 expression and increased HSF1 activation correlate with poor outcome in cancer, e.g., breast cancer.