(1158-C) Live Cell Painting: enhancing throughput and insights in drug discovery with a novel non-toxic, mix-and-read method for high-content screening
Tuesday, February 6, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Thanks to recent advances in bioimaging methods, the use of high-content screens is increasingly gaining popularity and thus accelerating the discovery of new therapeutic compounds [1,2]. However, due to the lack of biologically inert fluorophores, large-scale high-content screens are mostly performed on fixed cells, which can result in uneven sample alterations and the loss of crucial kinetic information. We present a method that uses a new non-toxic fluorophore with unique properties, which allow not only for the detection of distinct phenotypic fingerprints, but also for the assessment of different cell death mechanisms. In addition, the mix-and-read and non-toxic characters of this new fluorophore allow for more robust and higher-throughput assays, along with the ability to assess drug effects indefinitely over time. This work presents data on the biocompatibility of this method, and on its relative performance against cell painting – the gold standard image-based profiling method – for accurately predicting drug mechanism of action. Applications such as live kinetic imaging for quantifying various cell phenotypes such as apoptosis, autophagy, and ER stress are also presented. The rich information and robustness of this new method has potential to improve drug discovery throughput and provide new insights on drug mechanisms. [1] Oppermann, S., Ylanko, J., Shi, Y., Hariharan, S., Oakes, C. C., Brauer, P. M., ... & Andrews, D. W. (2016). High-content screening identifies kinase inhibitors that overcome venetoclax resistance in activated CLL cells. Blood, The Journal of the American Society of Hematology, 128(7), 934-947. [2] Vincent, F., Nueda, A., Lee, J. et al. Phenotypic drug discovery: recent successes, lessons learned and new directions. Nat Rev Drug Discov 21, 899–914 (2022). https://doi.org/10.1038/s41573-022-00472-w