The Opera Phenix Microscope for High Content Screening Applications

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The Crick is a partnership between the Medical Research Council, Cancer Research UK, the Wellcome Trust and three leading universities: UCL (University College London), Imperial College London and King's College London. The Crick aspires to be one of the world's leading medical research institutes. The Crick achieves operational and research efficiencies and economies-of-scale through centralised facilities and functions, known as Science Operations, that provide all researchers at the Crick, irrespective of affiliation, with access to cutting-edge equipment, animals for research and laboratory enabling functions such as the High Throughput Screening facility (HTS).Technical advances mean that it is now commonplace to be able to identify when genes have been altered or lost as part of ageing or a disease process. It is less obvious what effect this loss has on any individual cell and how it contributes to a disease. Indeed, understanding the functional roles for any gene in any particular cell or condition or how any gene normally contributes to the way a cell behaves or responds is still somewhat lacking. Fortunately, we now have reagents (called CRISPRs) that allow researchers to inactivate any gene of interest and assess the consequences of its loss on cell behaviour. The effect of gene loss on the cell is inferred from quantitative analysis of images taken of the cells when they are either growing and moving normally or when they have been challenged to respond to a stimulus. By measuring the properties of cells lacking a single gene, researchers can infer something about the role it might be playing in the cell as a whole. The HTS facility at the Crick has created a system that allows researchers to study the effect of gene loss on cell behaviour for hundreds to thousands of genes simultaneously, experiments referred to as screening.This proposal is for a microscope capable of automatically imaging and analysing the tens of thousands of samples that such experiments demand. This new microscope in conjunction with the CRISPR reagents gives us the opportunity to shed light on both the basic mechanisms of how genes control what cells do and potentially the role they play in important human diseases.