The HTSF is a state-of-the-art technological hub that performs high throughput screens of chemical and arrayed sgRNA CRISPR libraries. We provide lab space, cell culture facilities and a full suite of detection, robotic and imaging equipment designed to facilitate work in microwell plates (96-, 384- or 1536 well formats) to users engaged in small molecule and target discovery efforts. The HTSF also assists investigators in the design and development of screening assays that can use all currently available assay readouts and formats.
Currently CTS offers access to screening chemical libraries that total 110,000 distinct compounds, with the goal to build the library size to 250,000 compounds. CTS also provides access to human and mouse whole genome arrayed CRISPR libraries for target discovery work in immortalized cells, primary cells and stem cells from a variety of disease conditions. In addition, CTS incorporates AI/machine learning tools to initiate and assist in drug and target discovery and drug optimization.
CTS also provides services in target identification and validation using arrayed human and mouse sgRNA CRISPR libraries from Synthego. In these libraries, each gene in the mouse or human genome is targeted with three individual sgRNAs and arrayed as single gene knockouts (Kos), distributed as sets individually in each well of an array of 384-well plates. CRISPR whole-genome high-throughput screens performed with these libraries knock-out each gene in the whole mouse or human genome individually, to define changes in practically any phenotype that can be interrogated in cultured cells.
The HTSF at OUHSC provides investigators with the equipment, chemical libraries, arrayed sgRNA CRISPR libraries and expertise for performing both biochemical and cell-based screens using a variety of detection formats.
The HTS Core’s mission is to provide cost-effective and time-efficient access to HTS technology to all researchers in Oklahoma, from identifying a precise biological process to be targeted for interrogation, to the analysis of HTS data and the identification and validation of hits.
Services provided by the HTSF:
- Consultation on the design of high throughput assays (This is a crucial step in HTS that will determine the biological relevance of the compounds identified)
- Biological/biochemical assay optimization
- Development, testing and screening of small molecule or CRISPR libraries using cell-based high-content imaging, cell-based conventional or biochemical-based screens.
- Cherry-picking of potential lead compounds/candidate genes
- Development of secondary assays and counter-screens, validation of gene KO
- Identification of lead compound drug candidates or candidate genes
In small-molecule screens, lead compound candidates are then transferred to the CTS Laboratory of Biomolecular Structure and Function and/or the Drug Synthesis and Analysis Core for medicinal chemistry and small-molecule optimization.
In CRISPR whole-genome screens, candidate genes are validated individually. Confirmed hits enter a pipeline of bioinformatic analysis with advanced tools.