CELB40160

A key feature in the design pipeline of modern therapeutic agents is that they are first tested in a series of in vitro cell-based assays. Increasingly these assays are carried out using fluorescence microscopy, as this provides detailed subcellular information about their effects. The range of agents (both chemical and biological) under test is potentially vast, meaning that these cell-based assays must employ a high degree of automation at all stages. This technology is termed high content screening (HCS) microscopy. HCS can also be applied in fundamental cell biology to ask basic questions, on a single-cell level, relating to cell function and behaviour. This module provides a general overview of HCS and its use in cell-based research, requirements for sample preparation and critical aspects of how to develop a successful HCS assay. The important role of automation in HCS will also be addressed from cell seeding to liquid handling and image acquisition. Students will gain an insight into the most advanced and up-to-date cell analysis packages that allow extraction of data from individual cells in an accurate and reproducible manner. We will also discuss the critical aspect of long-term data storage. Multi-disciplinary case studies showing how HCS can be used to study cytotoxicity and gene function will also be explored in detail. Students will undertake focussed practicals that will allow hands-on experience of the theoretical aspects covered in the lectures. These will include design of a liquid handling protocol to automatically prepare multi-well plates, and acquisition of images using an automated microscope system. Students will also develop automated analysis routines that will allow graphical representation of data extracted from the images acquired.