Volumetric imaging for drug discovery
HCS captures cellular dynamics at subcellular spatial resolution. It has become important in early drug discovery, enabling scientists to test the effects of potential drugs on subcellular processes and structures. Until now, automated image processing, a critical and rate-limiting step in HCS work flow, has only captured two-dimensional structure. EU funding facilitated development of a state of the art three-dimensional (3D) image processing framework within the context of the project '3D image analysis tool development for high-content screening' (HCS IMAGING). Designed to take data from confocal microscopic image stacks, the software extracts multi-dimensional information and creates statistically valid lists of genes or compounds related to a given hypothesis. Application of this image processing platform has advanced numerous scientific areas already. Beneficiaries include hypertrophy of human cardiac muscle cells, reprogramming the function of secretory granules and the mechanisms of action of a type of bacteria. The collaborative studies have resulted in several high-profile publications. Further, the platform has been utilised in the drug discovery process to identify regulators of autophagy, a cellular process involved in neurodegenerative disorders. The molecules should help focus drug discovery from lead development and some of the related findings may lead to patents. The EU-funded HCS IMAGING project has advanced the state of the art of an already powerful cellular imaging tool. Enabling visualisation in 3D rather than only in 2D has opened a new window on the cellular and subcellular structures involved in health and disease. It is expected to usher in a new era of drug discovery with major impact on global health and quality of life.
Keywords
High content screening, cellular imaging, drug discovery, 3D, confocal microscopic, hypertrophy, autophagy, neurodegenerative
