Abstract: The disclosure is directed to methods and compositions for screening a library of aptamers for aptamers having a binding affinity to a target molecule. The methods and compositions described herein utilize a throughput approach that is able to simultaneously measure binding affinity and link the binding affinity to the identity (e.g., sequence) of the aptamer.

Abstract: The invention provides methods of performing multi-parameter analysis of single cells. Specifically, the present invention is based, in part, on leveraging a separation of reaction volume scales to conduct high-throughput single cell multi-parameter measurements and library preparation on the same single cell using double emulsion micro-droplets and sorting using flow cytometry.

Abstract: A method of measuring optical properties of a specimen includes generating illumination light at a plurality of illumination wavelengths and, for each of the plurality of illumination wavelengths, directing the illumination light to impinge on the specimen, collecting sample light passing through the specimen, and detecting the collected sample light using a polarization state analyzer to form a set of polarization channels. The method also includes receiving a calibration tensor, converting the set of polarization channels for each of the illumination wavelengths into Stokes parameter maps using the calibration tensor, denoising the Stokes parameter maps, and deconvolving the Stokes parameter maps to provide density, anisotropy, and orientation measurements of the specimen. The method can multiplex intrinsic density, anisotropy, and orientation measurements of the specimen and density, anisotropy, and orientation measurements of labeled fluorescent molecules.

Abstract: In one aspect, methods of generating human monoclonal antibodies that specifically binds to an allergen are provided. In some embodiments, the monoclonal antibodies are generated from sequences identified from isolated single B cells from a human subject who is allergic to the allergen.

Abstract: Provided are antibodies or antigen binding portions thereof that specifically bind Dengue virus, various compositions of such antibodies or antigen binding portions thereof, and methods of their use. Provided are such antibodies, fragments of such antibodies retaining Dengue virus-binding ability, pharmaceutical compositions including such antibodies or antigen binding fragments thereof, and diagnostic compositions including such antibodies or antigen binding fragments thereof. Also provided are isolated nucleic acids encoding such antibodies, amino acid sequences of such antibodies, and host cells transformed therewith. Additionally, provided are prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the disclosure.

Abstract: In one aspect, methods of generating human monoclonal antibodies that specifically binds to an allergen are provided. In some embodiments, the monoclonal antibodies are generated from sequences identified from isolated single B cells from a human subject who is allergic to the allergen.

Abstract: Provided are fusion proteins and modified proteins comprising a neutralizing polypeptide and an antibody (e.g., a non-neutralizing antibody) that specifically binds to an epitope in a conserved region of one or more coronavirus spike proteins. The fusion proteins and modified proteins are able to specifically bind to and neutralize a broad spectrum of coronaviruses, including SARS-CoV-2 and all known SARS-COV-2 variants of concern (e.g., the Delta and Omicron variants). Also provided are various compositions of such proteins, methods of their use, nucleic acids encoding such proteins or domains thereof, constructs, expression cassettes, and vectors containing such nucleic acids, and host cells capable of expressing these proteins or domains thereof. Additionally provided are prophylactic and therapeutic methods employing the fusion proteins and/or modified proteins of the disclosure.

Abstract: Described are methods related to a newly discovered alternative conformation of the SARS COV 2 Spike protein.

Abstract: The disclosure is directed to methods and compositions for screening a library of aptamers for aptamers having a binding affinity to a target molecule. Specifically, non-natural nucleotides can be introduced onto aptamers immobilized on the surface of beads. The non-natural nucleotides can then be subsequently chemically modified to include additional binding agents. For example, copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions can be used to introduce a wide range of binding agents onto non-natural nucleotides on beads.

Abstract: Described in this disclosure are CRISPRi systems and methods, along with the related compositions and kits, that combine modularity, stable genomic integration, and ease of transfer to diverse bacteria by conjugation. CRISPRi compositions, methods, systems and kits described herein allow for genetic dissection of bacteria, facilitating analyses of microbiome function, antibiotic resistances and sensitivities, as well as comprehensive screening for host-microbe interactions. Embodiments of the invention comprise compositions, methods, systems, and kits for CRISPRi-based repression of gene expression in bacteria.

Abstract: This disclosure provides data showing that LEFTY inhibits differentiation-promoting pathways such as BMP7/pSMAD5 in breast cancer cell lines, over and above its known role of inhibiting Nodal/pSMAD2. LEFTY competes with BMP7 to bind to its cell surface receptor BMPR2, leading to inhibition of pSMAD5. The LEFTY-BMPR2 interaction is dominant over BMP-BMPR2 in tumorigenic cells, resulting in diminished pSMAD status, whereas in non-tumorigenic cells, there is minimal LEFTY-BMPR2 interaction, increased BMP7-BMPR2 association, and elevated pSMAD. Compositions and methods for inducing or inhibiting expression and/or the activity of LEFTY and BMP proteins are described, which can be used in diagnosis and therapy of cancer and other conditions, and to promote proliferation of stem cells.

Abstract: A method of sample analysis is described comprising providing a sample comprising a plurality of endblocked polynucleotides, digesting the sample with one or more defined nucleic acid-directed endonuclease that targets a sequence of interest to produce a digested sample of polynucleotide fragments, wherein one or more of the fragments in the digested sample comprises: a sequence of interest and at least one ligatable end that has been generated by endonuclease cleavage; (c) enriching for fragments that contain the sequence of interest, wherein the one or more sequences of interest are enriched greater than 55 times, or greater than 750 times, their relative abundance in the sample; and (d) analyzing the enriched sample.

Abstract: The disclosure provides an optical probe comprising an optical waveguide attached to a molecular switch that produces an altered optical signal upon binding a target molecule. The disclosure also provides an optical sensor system comprising an optical probe, a light source configured to emit the excitation light to be coupled into the optical waveguide of the optical probe; and a detector.

Abstract: Methods and compositions are provided for the treatment of Alzheimer's Disease (AD) by administering to a patient a therapeutically effective amount of an agent that inhibits signaling mediated by a bone morphogenetic protein type 1A receptor (BMPR-1A) or bone morphogenetic protein type 2 receptor (BMPR-2). Also provided are methods and compositions to increase the rate of neural stem cell self-renewal.

Abstract: The present disclosure provides materials and methods for sequencing a tissue sample and that allows spatial information about the tissue to be recovered by sequencing approaches at a single cell level.

Abstract: Provided are fusion proteins including an amino acid sequence of an ectodomain of Spike protein of a coronavirus, such as SARS-CoV-2, joined to an amino acid sequence of a ferritin subunit polypeptide. Nanoparticles including such fusion proteins, with surface-exposed trimers of the ectodomain of the Spike protein of the coronavirus, are also provided. Also provided are nucleic acids and vectors encoding the fusion proteins, cells containing such nucleic acid and vectors, immunogenic compositions including the fusion proteins, the nanoparticles, or the vectors, as well as corresponding methods and kits.

Abstract: The present disclosure provides methods related to determining the level of afucosylated Fc glycans in IgG antibodies in a biological sample from a subject. This level can be used in methods aimed at monitoring and/or treating subject suffering from an acute flavivirus infection and/or who are at risk for progression to clinically significant infection or disease. This level can also be used in a vaccination method to ensure that those who receive a flavivirus vaccine have a reduced risk of reacting to the vaccine be developing clinically significant infection or disease. The disclosure also provides treatment methods based on inhibiting Fc?RIIA or Fc?RIIIA receptor signaling. Also provided are novel cell lines that are useful in measuring afucosylated Fc glycans.

Abstract: In one aspect, methods of generating human monoclonal antibodies that specifically binds to an allergen are provided. In some embodiments, the monoclonal antibodies are generated from sequences identified from isolated single B cells from a human subject who is allergic to the allergen.