Compound Screening and Profiling in Cultured Human (3D) Tissues
Recorded On: 09/26/2016
Cells grown in monolayer (2D) culture display a frantic rate of proliferation not seen in the most malignant of tumors. Aberrant gene expression profiles of cells grown on tissue culture plastic also reflect their loss of tissue-specific functions. But the culture of even highly transformed cancer cell lines in three dimensional extracellular matrix protein-rich environment can tame the cell cycle and restore some phenotypic and functional characteristics of the original patient tissue. For these reasons, 3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared to 2D cell cultures. In this webinar, however, we will skip over these important aspects to focus on an under-exploited characteristic of 3D tissues – their increased phenotypic complexity. The examination of tissue morphology by histopathologists is invaluable in the diagnosis of disease. Similarly, the morphology of 3D cultured tissues can also provide rich insight into the diseased state and the impact of drug treatment – both therapeutic and adverse. However, most users of 3D cell culture use simple readouts of cell viability which neglect the rich information that can be gained from image-based analysis. Just as different mutations can drive characteristically different phenotypes, disruption of different cellular pathways with drugs can also induce characteristic phenotypic responses. In this webinar, we discuss how this can be exploited, allowing drugs to be classified based on their target specificity and discriminating polypharmacology and off-target toxicities.
Leo Price, PhD.
Leo Price completed his PhD in Cell Physiology at University College, London (1995). After a postdoc at The Scripps Research Institute, he continued his research on cell adhesion signaling at the Netherlands Cancer Institute and University of Utrecht. From 2006, he was group leader at the Leiden Academic Centre for Drug Research at Leiden University in The Netherlands, where he further developed this research making extensive use of 3D cell culture models. In 2011 he founded OcellO, which provides high content tissue-based screening services to the drug discovery industry.