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Updated: Jan 18, 2026
08:51
Author Spotlight: Integrated Multi-Omics Analysis for Unveiling Multicellular Immune Signatures in Clinical Heart Attack Cohorts
Published on: September 20, 2024
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Making sense of low-complexity domains: The 2025 Lasker Basic Science Award.
1Sidney Farber Professor of Medicine, Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02116.
Summary
Low-complexity domains (LCDs) drive reversible phase separations in cells, forming essential molecular hubs. Mutations in these domains can lead to irreversible polymers and disease, highlighting their critical biological role.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- 10-20% of proteomes contain low-complexity domains (LCDs) with reduced amino acid diversity.
- These domains are crucial for cellular organization and function.
- Pioneering work by Steven McKnight and Dirk Görlich elucidated the function of LCDs.
Purpose of the Study:
- To investigate the role of low-complexity domains (LCDs) in cellular processes.
- To understand the mechanisms of phase separation driven by LCDs.
- To explore the implications of LCD mutations in disease.
Main Methods:
- Utilized various experimental approaches to study LCD interactions.
- Observed phase separation phenomena in vitro (hydrogels) and in vivo (P bodies, stress granules).
- Investigated the role of LCDs in nuclear pore complex (NPC) selectivity and nuclear transport.
Main Results:
- Demonstrated that LCDs mediate both homotypic and heterotypic interactions.
- Showed that these interactions lead to reversible phase separations, forming liquid condensates.
- Identified LCDs as critical components of molecular hubs for transcription and mRNA splicing.
- Revealed LCDs' role in the selectivity of nuclear pore complexes (NPCs).
Conclusions:
- LCDs are fundamental for reversible biomolecular phase separation and cellular organization.
- Aberrant LCD behavior, such as irreversible polymerization due to mutations, is linked to neurodegeneration and other diseases.
- Understanding LCDs is crucial for comprehending normal cellular function and disease pathogenesis.
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