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By Simon Fogarty
High throughput screening methods for phenotypic drug discovery are in demand, as novel disease models arise and increase in complexity. A main presentation track at SLAS2018 entitled "Automation and High-throughput Technologies" will include the session "Automating Target-Based and Complex Phenotypic Drug Discovery," chaired by Shane Horman, Ph.D. of the Genomics Institute of the Novartis Research Foundation. We spoke with Dr. Horman to learn more about the key topics, highlighted trends, and target audience for the session.
Phenotypic screening is increasingly being performed in 3D tissue models that simulate complex disease processes, such as the neurodegeneration underlying Alzheimer's disease.
Embracing complexity in phenotypic screening
Phenotypic assays have historically played an important role in drug discovery, but their adoption for high throughput and high-content applications can be challenging, particularly when they involve complex disease models
“I invited people to present who are working on the more troublesome and challenging tissue models, and developing innovative approaches to model those tissues in high throughput formats,” says Dr. Horman. "One session, for example, will focus on the challenges of using high-throughput confocal microscopy in three-dimensional tumor structures."
Another speaker will present on a high content method of modeling polycystic kidney disease. The kidney is arguably the most challenging organ to replicate. Whereas most of the high content 3D studies have been in the oncology area involving tumor modeling, this is new research in the regenerative medicine field.
"The other tissue that has been very challenging to model, especially in a high content fashion, is the brain. One of the talks will be on Alzheimer’s disease modeling with a high-throughput screening method using neurospheroids," said Horman.
Dr. Horman's own presentation will focus on immuno-oncology and, specifically, on enhancing T-cell mediated tumor killing.
Blueprint for success with high-throughput screening
Dr. Horman describes assay development as the blueprint, or "proving ground" for any successful screen. "When you look at the new technologies being rolled out you can truly appreciate the ability now to convert things like Sanger sequencing and next-gen sequencing (NGS) into screening formats." These types of technologies used to be separate from screening, but now high-throughput assays can be developed incorporating them.
"Epigenetic targets, for example, were more theoretical and amorphous compared to the hard, defined genetic targets that we had in the past. That's not true anymore, however, and we now have bona fide epigenetic drugs."
Opportunities for precision medicine
Advances in stem cell biology and the use of induced pluripotent stem cell (iPSCs) to study the exact defects and diseases that manifest in the human population is another important area of focus. "We can now capture these [defects] in cells, and fast-forward those cells to recapitulate the defects that appear in later generations, in adult patients. That creates screening opportunities for precision medicine that we have never had before."
Dr. Horman would encourage anybody involved in screening, tissue modeling, 3D cell models, cell-based drug discovery, kidney disease, Alzheimer's disease, and oncology to attend this session.
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