Phase Separation in Biology and Disease; Current Perspectives and Open Questions |
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| Institution: | 1. Department of Molecular and Human Genetics, Therapeutic Innovation Center (THINC), Center for Alzheimer’s and Neurodegenerative Diseases (CAND), Dan L Duncan Comprehensive Cancer Center (DLDCCC), Baylor College of Medicine, Houston, TX 77030, USA;2. Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA;3. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA;4. Michael Smith Laboratories, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada;5. New York University School of Medicine, Institute for Systems Genetics, New York, NY 10016, USA;6. Laboratory of Molecular Neuroscience, German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany;7. Dewpoint Therapeutics, Boston, MA, USA;8. School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore;9. Nereid Therapeutics, Boston, MA, USA;10. Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland;11. Laboratory of Nuclear Organization, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA;12. Department of Genetics, Stanford University, Palo Alto, CA 94304, USA;13. Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA;14. Department of Biological Sciences, Marquette University, Milwaukee, WI, USA;15. Department of Biology, Duke University, Durham, NC 27708, USA;16. University of Texas at Austin, Department of Biomedical Engineering, Austin, TX, USA;17. Department of Biology, McGill University, Montreal, QC H3A 1B1, Canada;18. Faze Medicines, Cambridge, MA, USA;19. Department of Biological Sciences, Mellon College of Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA;20. German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075 Göttingen, Germany;21. Max Planck Institute for Multidisciplinary Sciences, Department of NMR-based Structural Biology, Am Fassberg 11, 37077 Göttingen, Germany;22. Department of Biochemistry, The Graduate Center of the City University of New York, New York, NY, USA;23. Structural Biology Initiative, Advanced Science Research Center, City University of New York, New York, NY, USA;24. Department of Structural Biology, St. Jude Children''s Research Hospital, Memphis, TN, USA;25. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Sciences Center, Memphis, TN, USA |
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| Abstract: | In the past almost 15 years, we witnessed the birth of a new scientific field focused on the existence, formation, biological functions, and disease associations of membraneless bodies in cells, now referred to as biomolecular condensates. Pioneering studies from several laboratories reviewed in1, 2, 3] supported a model wherein biomolecular condensates associated with diverse biological processes form through the process of phase separation. These and other findings that followed have revolutionized our understanding of how biomolecules are organized in space and time within cells to perform myriad biological functions, including cell fate determination, signal transduction, endocytosis, regulation of gene expression and protein translation, and regulation of RNA metabolism. Further, condensates formed through aberrant phase transitions have been associated with numerous human diseases, prominently including neurodegeneration and cancer. While in some cases, rigorous evidence supports links between formation of biomolecular condensates through phase separation and biological functions, in many others such links are less robustly supported, which has led to rightful scrutiny of the generality of the roles of phase separation in biology and disease.4, 5, 6, 7 During a week-long workshop in March 2022 at the Telluride Science Research Center (TSRC) in Telluride, Colorado, ～25 scientists addressed key questions surrounding the biomolecular condensates field. Herein, we present insights gained through these discussions, addressing topics including, roles of condensates in diverse biological processes and systems, and normal and disease cell states, their applications to synthetic biology, and the potential for therapeutically targeting biomolecular condensates. |
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| Keywords: | phase separation biomolecular condensates membraneless organelles |
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