CZ Biohub SF, LLC

The present disclosure provides materials and methods for the continuous measurement of biomolecules in vivo and in real-time. The present disclosure relates more specifically to using capture agents and detection agents within a microfluidic device to detect and quantify biochemical features of biomarkers, enabling real-time detection and concentration measurements.

A novel ubiquitous chromatin opening element (UCOE) named SRF-UCOE and methods for its use are provided. Compositions including recombinant and synthetic SRF-UCOE nucleic acid molecules, DNA constructs and vectors comprising the SRF-UCOE nucleic acid molecules, host cells comprising the DNA constructs or vectors, and cell culture systems comprising such host cells. SRF-UCOE polynucleotide sequences can be used in DNA constructs or expression cassettes for transformation and expression in cells or organisms of interest. The compositions and methods provided are useful for increasing and/or maintaining expression of a gene of interest. Transgenic cells, tissues, and animals comprising a SRF-UCOE nucleotide sequence are also provided. Methods are provided for increasing and/or maintaining expression of a gene of interest and for treating a subject via gene therapy.

Methods for characterizing a population of microbes in a sample are described. The methods include: amplifying microbial polynucleotides obtained from the sample to form a plurality of amplicons and combining the amplicons with a plurality of microbeads, wherein each of the microbeads has a lanthanide spectral signature paired with the sequence of capture polynucleotides immobilized on the microbead. At least some of the capture polynucleotides comprise a sequence substantially complementary to a microbe-identifying sequence in one or more amplicons, such that at least some amplicons are captured onto beads by the capture polynucleotides and the microbe can be identified based on the lanthanide spectral signature of with which the capture polynucleotide is paired. Further described are methods for the identification of pathogens present in a sample by evaluating patterns of hybridization of a capture oligonucleotide to amplicons. Microbead compositions and methods for the preparation thereof are also described.

Tobacco etch virus protease (TEV) is one of the most widely used proteases in biotechnology because of its exquisite sequence-specificity. A limitation of TEV is its slow catalytic rate, which limits product generation and therefore signal output. Provided is a generalizable yeast-based platform for directed evolution of protease catalytic properties. Protease activity is determined via proteolytic release of a membrane-anchored transcription factor, and access to TEV's cleavage site is temporally regulated using a photosensory LOV domain. By gradually decreasing light exposure time, faster variants of TEV were selected over multiple rounds of selection. The mutant TEV proteases and the directed evolution platform are useful in a wide range of biotechnology applications, such as FLARE and SPARK tools.

Various embodiments are directed to analyzing host gene expression levels and microbial diversity in a biological sample, to determine a likelihood of lower-respiratory tract infection (LRTI) in subjects. Embodiments can include determining a probability value of a subject having LRTI based on differential gene expression of the subject and reference levels of control subjects. Embodiments can also include determining the likelihood of LRTI in subjects based on amicrobial diversity index or abundance levels of microbes that are considered as potential pathogens. Embodiments can also include applying an integrated classifier to gene expression levels, virus abundance levels, and microbial diversity to determine the likelihood of LRTI in subjects.

Organoid culture and image-processing methods and systems are described. Such methods and systems provide the ability for high-throughput characterization of a variety of phenotypes at single-organoid resolution.

The disclosure provides aptamer switch polynucleotides whose kinetics and effective binding affinity to a target analyte can be independently tuned. The aptamer switch polynucleotides comprise an aptamer, an intramolecular linker, and a displacement strand.

A method of measuring malarial parasitemia includes disposing a sample including red blood cells in liquid form on a sample stage, illuminating the sample with optical radiation, capturing a plurality of images of the sample, and extracting, from the one or more of the plurality of images, a set of red blood cell images. Each red blood cell image is associated with a particular red blood cell. The method also includes for each red blood cell image in the set of red blood cell images, inputting each red blood cell image into a machine learning model and generating, using the machine learning model, a classification related to a malaria parasite lifecycle stage for each of the red blood cells. The method further includes determining the malarial parasitemia for the sample.

The invention is directed to methods of identifying woman is risk for preterm delivery. In some aspects, the methods include quantitating one or more placental or fetal-tissue specific genes in a biological sample from the woman.

This disclosure describes methods and compositions for detecting the presence of a Kelch-like protein 11 autoantibody in a biological sample. Also provided are methods of treating subjects with testicular cancer or a premalignant condition and paraneoplastic encephalomyelitis.