The Power of High Content, High-Throughput Screening in Condensate-Based Drug Discovery
Sponsored by HighRes® Biosolutions
Historically, single target approaches are employed to discover drugs for complex diseases including oncology, neurodegenerative, and metabolic diseases. In the traditional R&D pipeline, high-throughput screening (HTS) begins at the protein level, which can be performed via plate readers with various detection methods such as absorbance or luminescence to identify compounds that modulate the activity of the intended target, but often fail to correct the full complexity of the disease.
Biomolecular condensates are membrane-less organelles that form via phase separation and are responsible for a wide range of cellular functions such as protein shuttling2, RNA binding1, and cell signaling3. When disrupted in disease, they lead to complex pathophysiology. We now understand that condensates serve as central nodes of dysfunction in many diseases, termed ‘condensatopathies’. Repairing the condensatopathy reverses complex disease markers [NRDD]. Condensate dysfunction is generally accompanied by morphological changes that can be detected by microscopy.
Condensate biology is an emerging field in the world of phenotypic screening. By monitoring phenotypic changes in condensates by high content imaging, this approach promises to identify novel classes of condensate-modifying drugs (c-mods) that correct the condensatopathy in difficult to treat disease. Working with cells in earlier stages of screening presents unique challenges to overcome when streamlining and optimizing any HTS campaign. Protocol complexity, rate limiting steps (such as long imaging times and instrumentation timing), and robotic design are all key factors when it comes to planning phenotypic high content HTS. Herein, we describe how Dewpoint Therapeutics addresses the challenges associated with phenotypic HTS in the field of condensate biology including protocol design, assay design, and system design.
Learning Objectives:
1. The benefits of multiplexing protocols
2. Assay design decisions based on consistency AND biological relevance rather than just one or the other
3. System design to accommodate high-content imaging
Privacy Policy
Outside of work, Crystal is teaching two graduate-level courses at Northeastern University, where she graduated with her Master’s degree in Biotechnology with a concentration in Pharmaceutical Technologies. She also volunteers regularly with undergraduate and high school students in underserved communities. Outside of science, Crystal enjoys eating, reading, snacking, training the turtle and dog to do tricks that will annoy her husband, and her roller derby league!
