Chapter 3: The Development and Use of Protein and Protein-affinity Libraries for Phenotypic Screening

Physiological and disease processes are regulated by proteins at a systemic, organ and cellular level. Gaining a deeper understanding of these processes and the proteins involved will lead to hypotheses for therapeutic intervention in areas of high unmet medical need. This chapter describes different approaches to using proteins and protein affinity tools in conjunction with relevant cellular phenotypic assays with the aim of identifying new targets for drug discovery. Different types of protein tools are described, including approaches to generating libraries for screening and the potential uses and advantages associated. Practical considerations for sample management, screening strategies and deconvolution of results are described, together with a discussion on how data from these approaches might impact the discovery of targets for drug discovery in the future. In addition, we describe a case study, in which a library of purified, secreted proteins was screened in a cell-based phenotypic assay. This work exemplifies some of the data generated and how it can be used to develop new hypotheses for drug discovery.