Harnessing the power of fluorescence to characterize biomolecular condensates

Levin, Benjamin; Mittasch, Matthäus; Gomes, Beatriz Ferreira; Manteiga, John C.; Patel, Avinash; Zamudio, Alicia V.; Beutel, Oliver; Mitrea, Diana M.

doi:10.1016/bs.mim.2020.11.005

Cited by 1 publication

(3 citation statements)

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“…Typically, live-cell fluorescence confocal microscopy is used to characterize the localization and emergent properties of condensates (reviewed in ref. 179 ). Condensates with sizes below the limit of detection of conventional confocal microscopes 136 , 180 , 181 may be visualized, albeit at the expense of speed and throughput, with the advanced techniques 182 described in Box 3 .…”

Section: Building a C-mod Discovery Platformmentioning

confidence: 99%

“…For example, monitoring the shift in the phase boundary and changes in emergent biophysical properties (such as number, size, morphology, material properties, dynamics and composition) as a function of various parameters (such as ionic strength, pH, ligand concentration and temperature) could identify the most promising points for therapeutic intervention inside the macromolecular network (reviewed in ref. 179 ). This informs strategies for c-mod design (for example, a protein–ligand interaction, a hydrophobic-driven interaction or an electrostatically driven interaction) and hit optimization.…”

Section: Building a C-mod Discovery Platformmentioning

confidence: 99%

“…These engineered systems and practical considerations for their selection are reviewed in ref. 179 .…”

Section: Building a C-mod Discovery Platformmentioning

confidence: 99%

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Modulating biomolecular condensates: a novel approach to drug discovery

Mitrea¹,

Mittasch²,

Gomes³

et al. 2022

Nat Rev Drug Discov

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107

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In the past decade, membraneless assemblies known as biomolecular condensates have been reported to play key roles in many cellular functions by compartmentalizing specific proteins and nucleic acids in subcellular environments with distinct properties. Furthermore, growing evidence supports the view that biomolecular condensates often form by phase separation, in which a single-phase system demixes into a two-phase system consisting of a condensed phase and a dilute phase of particular biomolecules. Emerging understanding of condensate function in normal and aberrant cellular states, and of the mechanisms of condensate formation, is providing new insights into human disease and revealing novel therapeutic opportunities. In this Perspective, we propose that such insights could enable a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and we discuss the strategies, techniques and challenges involved.

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