Further development and application of the E-Morph assay to detect of substance effects based on morphological fingerprints by HT/HC screening

As early as 160 years ago, Rudolf Virchow described in his concept of "Cellularpathology" that diseases such as cancer are also reflected in changes in the form - the morphology - of cells (Virchow, 1855). Today, modern microscopes and robotics-supported high-throughput methods deliver a large number of cell images in a very short time, which can be automatically evaluated using special image analysis methods. In addition, with the help of novel staining methods - such as "Cell Painting" - a wide variety of cell components can be made visible at the same time. The information about the internal and external morphology of cells obtained in the course of such procedures makes it possible, among other things, to determine how drugs work, but also to identify undesired effects that can be caused by pollutants. These include, for example, hormonal chemicals in the environment, in food or clothing, which, as so-called endocrine disruptors, disrupt the body's hormone system and thus are hazardous to human health. These substances are currently being examined primarily in complex animal experiments, which require a large number of test animals and, due to the lack of transferability to humans, are sometimes only of limited significance. In the MORPHEUS (MORPHology-based Endocrine disruptor Screening) project, we want to expand the scope of a cell-based high-throughput method - the E-Morph Assay - (Kornhuber et al.short foret alii (lat. "and others"), 2021) and use "cell painting" and methods of artificial intelligence to detect characteristic changes in the Identify cell morphology induced by substances with hormonal effects. With the help of these "morphological fingerprints" we want to develop computer models that will make it possible to predict possible hormonal effects of chemicals in the future and thus avoid unnecessary animal experiments.