Cell Imaging for basic research and drug discovery programs in academic and non-profit enviroments.

The ability to test, on a large scale, the phenotypic consequences of treating cells with large numbers of genetic or chemical perturbations represents a substantial new asset in the cell biologists’ toolbox. Academic biologists, interested in a specific function, can systematically knock-down the expression of all the genes in a genome to identify those whose alteration modifies a specific functional readout. Application-oriented scientists, on the other hand, can screen a large number of chemicals to identify potential drug leads that revert a pathological phenotype. Thus, many academic and non-profit organizations are exploring these new high-content phenotypic approaches for medium-to-large gene screening or drug discovery programs. As with many new high-content technological approaches, however, the necessary technology and infrastructure is not immediately available to all interested parties since assay development may often require resources, interdisciplinary competency, or sophisticated infrastructure that are not readily available to small academic groups and non-profit organizations. The HT/HCA facility at Consorzio Mario Negri Sud (http://www.negrisud.it/it/ricerca/servizi/htmicroscopy/) was planned to provide the core infrastructure and competence for high-throughput high-content image analysis for academic and non-profit researchers involved in cancer and monogenic disease research located in the center of Italy. We offer the technology, laboratory space and technical support, not only to perform mid-size screens (up to 1200 compounds or siRNA library) but also to assist in the development of disease-relevant cell-based assays for screening. A bioinformatics and statistical group joined us recently in this project to support the processing of the image analysis and its integration with orthogonal genome-wide information. As proofs of concept, we have undertaken a series of collaborations and generated a number of cell-based assays over the past two years with Italian groups working in academia or non-profit environments. The results of these collaborations will be presented.