3D HCS IMAGING

3D image analysis tool development for high-content screening

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 Obiettivo del progetto (Objective)

'Recently both academic institutions and the pharmaceutical industry have identified 3 dimensional (3D) cellular model systems as one of the most important areas of future development in drug discovery programs and cell-based screening. High-content screening (HCS) platforms with large-scale automation and data analysis are extensively used in such programs. Automated image processing is a critical and rate-limiting step in HCS workflows that can be resolved by computational approaches. However, this has currently only been approached in a 2D manner and would benefit hugely from the ability to extend into 3D analyses.

I plan to develop a 3D image processing-statistical framework with emphasis on 3D segmentation that can be highly useful for numerous researchers working in biomedical and molecular biological fields. This project is based on my previous expertise in developing a high-content analysis pipeline around 2D image segmentation. Any current areas of research that use traditional microscopic high-throughput analyses have the potential to benefit from this tool. These include microscopic model organisms and mammalian cell research. This software will not be limited to fluorescence microscopy, but can also be applied to other platforms such as electron microscopy and in vivo imaging of animals. I will expand and characterize the means by which 3D image segmentation enables the analysis of these models in large-scale.

Continuing my previous research, one interesting application is the study of autophagy in MCF-10A mammary epithelial cells that is an easy and tractable 3D model system used in drug screening for the pathogenesis of epithelial tumours.

In summary, the development of 3D imaging tools will move the field of high-content analysis forward and open a new dimension to HCS methodologies that I hope will find its way into standard protocols. The successful completion of this project will enable me to become a leading expert in this field within Europe.'

Introduzione (Teaser)

High content screening (HCS) or quantitative cellular imaging is a powerful method for studying many features simultaneously in complex biological systems. EU-funded scientists have given it a new dimension for major impact.

Descrizione progetto (Article)

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.