Project title: Screening of HDAC Inhibitors with Single-Cell Transcriptome and Epigenome Readouts.

The scientific activity under Miniatura research grant is a pilot study aimed at testing the profiling of cancer cells’ responses to selected chemical compounds at single-cell and single-clone resolution, with full determination of changes in the transcriptome and chromatin availability after drug administration. The study is divided into successive stages. Initially, a protocol for labeling cell nuclei populations with joint profiling of transcriptome changes and chromatin accessibility will be established. Then, using a high-throughput screening (HTS) platform, the effect of selected histone deacetylase inhibitors (HDACi) in different concentrations on the response of four human cancer lines representing some of the most common types of cancer (breast, lung, colorectal, prostate) will be investigated. Each individual experimental condition will be coded and then grouped to perform multiomics studies within single cells. Separate libraries will be sequenced to generate a dataset containing common transcriptome and chromatin accessibility profiles for each of the experimental conditions, respectively. This will allow future cost-effective HTS with single-cell phenotyping.  The total funding of the project is 49 400 PLN.