Compositions and methods are provided for the identification of peptide sequences that are ligands for a T cell receptor (TCR) of interest, in a given MHC context.

A system and method for detecting interactions between a first protein or fragment thereof (bait protein) and a second protein or fragment thereof (prey protein) comprising: (a) a bait construct comprising the bait protein, a first epitope tag and an intein N-terminal fragment (IN); and (b) a prey construct comprising the prey protein, a second epitope tag, and an intein C-terminal fragment (IC).

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to improved TfR-binding moieties capable of crossing the blood brain barrier (BBB) and capable of carrying and releasing cargo specifically targeted to the parenchymal tissue of the brain. The present invention relates to a transcytosis selection method to obtain VNARs against mammalian blood brain barrier (BBB) receptors using phage display libraries as well as against receptors found in other directional cell barrier systems like the gastrointestinal tract and other organs. The VNARs may be used alone or as components in compositions or as conjugates that target the particular receptor transport systems for delivery of therapeutics or diagnostics to the brain (in the case of BBB receptors) or other tissues.

A radical departure from the classical E1-E2-E3 three-enzyme mediated ubiquitination of eukaryotes, the bacterial enzymes of the SidE family of Legionella pneumophila effectors utilize NAD.sup.+ to ligate ubiquitin onto target substrate proteins achieved via a two-step mechanism involving (1) ADP-ribosylation of ubiquitin followed by (2) phosphotransfer to a target serine residue. Using fluorescent NAD.sup.+ analogues as well as synthetic substrate mimics, a continuous assay system enabling real-time monitoring of both steps of this mechanism is disclosed herein. These assays are amenable to biochemical studies and high-throughput screening of inhibitors of these effectors, and enable the discovery and characterization of putative enzymes similar to the SidE family in other organisms. A kit of the assay system, for real-time monitoring protein ubiquitination and/or identifying an inhibitor for protein ubiquitination comprising a fluorescent NAD+ analogue and a synthetic substrate mimic, is also in the scope of this disclosure.

The present invention generally relates to bacterial polypeptide display systems, libraries using these bacterial display systems, and methods of making and using these systems, including methods for improved display of polypeptides on the extracellular surface of bacteria using circularly permuted transmembrane bacterial polypeptides that have been modified to increase resistance to protease degradation and to enhance polypeptide display characteristics.

The presently disclosed subject matter provides methods and compositions for treating myeloid disorders (e.g., acute myeloid leukemia (AML)). It relates to immunoresponsive cells bearing antigen recognizing receptors (e.g., chimeric antigen receptors (CARs)) targeting AML-specific antigens.

Provided herein are, inter alia, methods of identifying agents that are capable of inhibiting the binding (e.g., coupling) between a ROR1 protein and a ROR2 protein. By interfering with ROR1-ROR2 coupling (binding) the agents identified using the methods provided herein inhibit non-canonical Wnt5a signaling. Thus, the agents identified by the methods provided herein may, inter alia, be useful for cancer diagnosis and therapy.

Disclosed are methods for obtaining cells that express antibodies that bind transmembrane proteins, methods for generating antibodies from such cells, antibodies to transmembrane proteins and fragments thereof, and nucleic acids encoding the antibodies. More particularly, the disclosure relates to methods for obtaining antibody-producing cells that express an antibody that binds to a transmembrane protein based on the use of lipid bilayer-membrane scaffold protein complexes to present transmembrane protein antigens to cells.

Research tool assay for identifying a specific modulator of GNAI, compositions and methods of use. The assay includes combining a drug candidate with GNAI and a C-terminal GIV peptide and determining if the drug candidate inhibits GNAI interaction with the C-terminal GIV peptide; and combining the drug candidate with GNAI and a DAPLE peptide and determining if the drug candidate inhibits GNAI interaction with DAPLE peptide. Also provided are compositions and methods of treatment relating to the same.