Marta Frigole-Vivas: “Biomolecular condensates: a novel opportunity for drug discovery”
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Author Marta Frigole-Vivas
The Society for Laboratory Automation and Screening (SLAS) invited Dewpoint Scientist Dr. Marta Frigolé-Vivas to give a webinar about drugging condensates on June 3, as part of the SLAS online learning center. If you missed the live event, SLAS has generously shared the recording of the event below.
Abstract
Biomolecular condensates are membraneless organelles that compartmentalize biomolecules such as proteins and nucleic acids (Banani et al. Nat Rev Mol Cell Biol 2017). In contrast to classical membrane-bound organelles, condensates are dynamic and reversible compartments that often form by liquid-liquid phase separation (LLPS). LLPS is a physicochemical process by which biomolecules demix into two separate phases through multivalent interactions between nucleic acids, tethered multivalent protein domains, and intrinsically disordered proteins.
Biomolecular condensates regulate and compartmentalize an ever-increasing number of cellular functions including RNA metabolism, transcription, and signal transduction, among others (Alberti et al. Cell 2019). Altering the concentration, post-translational modification, or sequence of condensate components can modulate condensates with functional consequences. Thus, biomolecular condensates have been implicated in diseases such as neurodegeneration, cancer, and infectious diseases (Alberti and Dormann. Ann Rev Gen 2019). We find that aberrant condensates drive many multifactorial diseases.
Focusing drug discovery efforts on condensates presents novel opportunities for therapeutic development (Wheeler. Emerg Top Life Sci 2020). In this presentation we will discuss different approaches by which condensate modulating drugs, or c-mods, that alter the composition, stability or dissolution of condensates can prevent or reverse disease. Initial results from a condensate-based screen to identify c-mods with potential therapeutic activity for amyotrophic lateral sclerosis (ALS) will be presented.
Marta Frigolé, Ph.D., Scientist, Dewpoint Therapeutics
Marta Frigolé-Vivas is a scientist at Dewpoint Therapeutics. She has a background in medicinal chemistry and condensate biology. She is passionate about leveraging condensate biology to develop novel drugs for currently unmet medical needs.