Abstract: Compositions and methods for targeted treatment of cancer are disclosed. In particular, the invention relates to methods of targeting anti-cancer therapy to cells exhibiting aberrant signaling associated with cancer pathogenesis by administering synthetic signaling proteins that couple detection of an oncogenic signal to release of therapeutic agents into cancerous cells.

Abstract: Provided are protease inhibitor compounds that find use in treating or preventing coronavirus disease. In some embodiments, the coronavirus disease is COVID-19. Also provided are compositions and kits comprising the compounds, as well methods of using the compounds to treat or prevent coronavirus disease. Methods of assessing inhibition of coronavirus protease activity by an agent are also provided.

Abstract: Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

Abstract: Provided herein are compositions and methods for inducing protein function. For example, in some embodiments, provided herein are compositions and methods for pharmacological induction of protein function.

Abstract: Engineered fusion proteins comprising a self-excising degron for controlling protein production are disclosed. In particular, the inventors have constructed fusion proteins comprising a degron connected to a protein of interest through a cleavable linker comprising a hepatitis C virus (HCV) protease site. The degron can be removed from the protein of interest by a cis-encoded HCV protease such that the protein of interest can be produced with minimal structural modification. Clinically available HCV protease inhibitors can be used to block protease cleavage such that the degron is retained after inhibitor addition on subsequently synthesized protein copies. The degron when attached causes rapid degradation of the linked protein. Such fusions of a degron to a protein of interest will be especially useful when control over protein production with minimal structural modification is desired.

Abstract: Engineered fusion proteins comprising a self-excising degron for controlling protein production are disclosed. In particular, the inventors have constructed fusion proteins comprising a degron connected to a protein of interest through a cleavable linker comprising a hepatitis C virus (HCV) protease site. The degron can be removed from the protein of interest by a czs-encoded HCV protease such that the protein of interest can be produced with minimal structural modification. Clinically available HCV protease inhibitors can be used to block protease cleavage such that the degron is retained after inhibitor addition on subsequently synthesized protein copies. The degron when attached causes rapid degradation of the linked protein. Such fusions of a degron to a protein of interest will be especially useful when control over protein production with minimal structural modification is desired.

Abstract: Compositions and methods for targeted treatment of cancer are disclosed. In particular, the invention relates to methods of targeting anti-cancer therapy to cells exhibiting aberrant signaling associated with cancer pathogenesis by administering synthetic signaling proteins that couple detection of an oncogenic signal to release of therapeutic agents into cancerous cells.

Abstract: Compositions and methods for targeted treatment of cancer are disclosed. In particular, the invention relates to methods of targeting anti-cancer therapy to cells exhibiting aberrant signaling associated with cancer pathogenesis by administering synthetic signaling proteins that couple detection of an oncogenic signal to release of therapeutic agents into cancerous cells.

Abstract: Engineered fusion proteins comprising a self-excising degron for controlling protein production are disclosed. In particular, the inventors have constructed fusion proteins comprising a degron connected to a protein of interest through a cleavable linker comprising a hepatitis C virus (HCV) protease site. The degron can be removed from the protein of interest by a czs-encoded HCV protease such that the protein of interest can be produced with minimal structural modification. Clinically available HCV protease inhibitors can be used to block protease cleavage such that the degron is retained after inhibitor addition on subsequently synthesized protein copies. The degron when attached causes rapid degradation of the linked protein. Such fusions of a degron to a protein of interest will be especially useful when control over protein production with minimal structural modification is desired.

Abstract: Fluorescent protein voltage sensors for measuring membrane potential and imaging high-frequency neuronal electrical activity are disclosed. In particular, the invention relates to engineered protein voltage sensors that comprise a voltage-sensing domain comprising four transmembrane domains linked to a circularly permuted fluorescent protein, which is inserted into the extracellular loop between the third (S3) and fourth (S4) transmembrane segments of the voltage-sensing domain. Such fluorescent protein voltage sensors can be used for measuring the electrical activity of neurons, including single action potentials, trains of action potentials, and subthreshold potential changes and, in particular, for imaging high-frequency neuronal electrical activity.

Abstract: Fluorescent protein voltage sensors for measuring membrane potential and imaging high-frequency neuronal electrical activity are disclosed. In particular, the invention relates to engineered protein voltage sensors that comprise a voltage-sensing domain comprising four transmembrane domains linked to a circularly permuted fluorescent protein, which is inserted into the extracellular loop between the third (S3) and fourth (S4) transmembrane segments of the voltage-sensing domain. Such fluorescent protein voltage sensors can be used for measuring the electrical activity of neurons, including single action potentials, trains of action potentials, and subthreshold potential changes and, in particular, for imaging high-frequency neuronal electrical activity.

Abstract: The disclosure provides method and compositions for visualizing protein turnover. In particular, the disclosure provides methods and compositions useful for measuring the age of particular proteins or the dynamics of localized protein translation.

Abstract: Engineered fusion proteins comprising photochromic protein domains are disclosed. In particular, the inventors have constructed fusion proteins containing photoswitchable photochromic fluorescent protein domains linked to selected proteins and shown that such fusion proteins can be used to control the activity or localization of selected proteins with light.

Abstract: The disclosure provides method and compositions for visualizing protein turnover. In particular, the disclosure provides methods and compositions useful for measuring the age of particular proteins or the dynamics of localized protein translation.

Abstract: The present invention relates to novel fluorescent protein variants of DsRed and eqFP578. Fluorescent protein variants having increased photostability and/or having reversible photoswitching behavior, as well as polynucleotides encoding such variants are provided herein. Methods of using these novel fluorescent protein variants and methods for constructing other fluorescent protein variants having increased photostability are also provided by the present invention.