Phase Separation in Biology and Disease; Current Perspectives and Open Questions
- Creators
- Boeynaems, Steven
- Chong, Shasha
- Gsponer, Jörg
- Holt, Liam
- Milovanovic, Dragomir
- Mitrea, Diana M.
- Mueller-Cajar, Oliver
- Portz, Bede
- Reilly, John F.
- Reinkemeier, Christopher D.
- Sabari, Benjamin R.
- Sanulli, Serena
- Shorter, James
- Sontag, Emily
- Strader, Lucia
- Stachowiak, Jeanne
- Weber, Stephanie C.
- White, Michael
- Zhang, Huaiying
- Zweckstetter, Markus
- Elbaum-Garfinkle, Shana
- Kriwacki, Richard
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 in 1, 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. 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.
Additional Information
© 2023 The Authors. Published by Elsevier Under a Creative Commons license - Attribution 4.0 International (CC BY 4.0). S.B. acknowledges funding from CPRIT (RR220094) and WALII (NSF DBI grant # 2213983). S.C. acknowledges support from the Shurl and Kay Curci Foundation Research Grant, Pew-Stewart Scholars Program for Cancer Research (00036068), Searle Scholars Program (SSP-2022-108), and Merkin Innovation Seed Grant. S.E-G. acknowledges support from NIH (R35NS111604), AFoSR (MURI GRANT12936019) and Alfred P. Sloan Foundation (CUNY JFRASE G-2018-11286). R.W.K. acknowledges support from NIH (NCI Cancer Center Support Grant, P30 CA021765; NCI R01 CA246125; and NCI FusOnC2 U54 CA243124) and ALSAC. D.M. is supported by the start-up funds from DZNE and the German Research Foundation (SFB 1286/B10 and MI 2104). C.D.R. was supported by an EMBO Postdoctoral Fellowship (ALTF 385-2022) and an SNSF Swiss Postdoctoral Fellowship (TMPFP3_210662). B.R.S acknowledges support from CPRIT (RR190090) and NIH (GM147583). S.C.W. acknowledges support from NSERC (RGPIN-2017-04435), CIHR (PJT-159580), and the Canada Research Chairs program. H.Z. acknowledges support from NIH (NCI 5U01CA260851). M.Z. was supported by the European Research Council (ERC) under the EU Horizon 2020 research and innovation programme (grant agreement No. 787679). J.S. acknowledges support from NIH (R01GM099836, R01GM138690, R21AG079609, and R21AG065854), Target ALS, AFTD, ALSA, the Office of the Assistant Secretary of Defense for Health Affairs through the Amyotrophic Lateral Sclerosis Research Program (W81XWH-20-1-0242), Sanofi, and the G. Harold and Leila Y. Mathers Foundation. The authors acknowledhe Akshita Chhabra at the German Center for Neurodegenerative Diseases (DZNE) for assistance with Figure 2. CRediT authorship contribution statement. Steven Boeynaems: Writing – original draft, Writing – review & editing. Shasha Chong: Writing – original draft, Writing – review & editing. Jörg Gsponer: Writing – original draft, Writing – review & editing. Liam Holt: Writing – original draft, Writing – review & editing. Drago Milovanovic: Writing – original draft, Writing – review & editing. Diana M. Mitrea: Writing – original draft, Writing – review & editing. Oliver Mueller-Cajar: Writing – original draft, Writing – review & editing. Bede Portz: Writing – original draft, Writing – review & editing. John F. Reilly: Writing – original draft, Writing – review & editing. Christopher D. Reinkemeier: Writing – original draft, Writing – review & editing. Benjamin R. Sabari: Writing – original draft, Writing – review & editing. Serena Sanulli: Writing – original draft, Writing – review & editing. James Shorter: Writing – original draft, Writing – review & editing. Emily Sontag: Writing – original draft, Writing – review & editing. Lucia Strader: Writing – original draft, Writing – review & editing. Jeanne Stachowiak: Writing – original draft, Writing – review & editing. Stephanie C. Weber: Writing – original draft, Writing – review & editing. Michael White: Writing – original draft, Writing – review & editing. Huaiying Zhang: Writing – original draft, Writing – review & editing. Markus Zweckstetter: Writing – original draft, Writing – review & editing. Shana Elbaum-Garfinkle: Writing – original draft, Writing – review & editing, Project administration. Richard Kriwacki: Writing – original draft, Writing – review & editing, Project administration. Declaration of Competing Interest. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.M.M. is an employee and shareholder of Dewpoint Therapeutics; B.P. is an employee and shareholder of Dewpoint Therapeutics; J.F.R. is an an officer and shareholder of Nereid Therapeutics; J.S. is a consultant for Dewpoint Therapeutics, ADRx, and Neumora, and a shareholder and advisor for Confluence Therapeutics; L.C.S. is on the Prose Foods Scientific Advisory Board; M.W. was an employee and shareholder of Faze Medicines when this article was conceived and initially written, and currently is an employee of IDEXX Laboratories; R.K. reports personal fees from Dewpoint Therapeutics, GLG Consulting, and New Equilibrium Biosciences outside the submitted work.Attached Files
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Accepted Version - nihms-1872500.pdf
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Additional details
- PMCID
- PMC9970028
- Eprint ID
- 120690
- Resolver ID
- CaltechAUTHORS:20230404-290277800.12
- Cancer Prevention and Research Institute of Texas
- RR220094
- NSF
- DBI-2213983
- Shurl and Kay Curci Foundation
- Pew Charitable Trusts
- 00036068
- Searle Scholars Program
- SSP-2022-108
- Caltech Merkin Institute for Translational Research
- NIH
- R35NS111604
- Air Force Office of Scientific Research (AFOSR)
- 12936019
- Alfred P. Sloan Foundation
- G-2018-11286
- NIH
- P30 CA021765
- NIH
- R01 CA246125
- NIH
- U54 CA243124
- American Lebanese Syrian Associated Charities
- Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
- Deutsche Forschungsgemeinschaft (DFG)
- SFB 1286/B10
- Deutsche Forschungsgemeinschaft (DFG)
- MI 2104
- European Molecular Biology Organization (EMBO)
- ALTF 385-2022
- Swiss National Science Foundation (SNSF)
- TMPFP3_210662
- Cancer Prevention and Research Institute of Texas
- RR190090
- NIH
- GM147583
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- RGPIN-2017-04435
- Canadian Institutes of Health Research (CIHR)
- PJT-159580
- Canada Research Chairs Program
- NIH
- 5U01CA260851
- European Research Council (ERC)
- 787679
- NIH
- R01GM099836
- NIH
- R01GM138690
- NIH
- R21AG079609
- NIH
- R21AG065854
- Target ALS
- Association for Frontotemporal Degeneration (AFTD)
- ALS Association
- Office of the Assistant Secretary of Defense for Health Affairs
- W81XWH-20-1-0242
- Sanofi
- G. Harold and Leila Y. Mathers Charitable Foundation
- Created
-
2023-05-09Created from EPrint's datestamp field
- Updated
-
2023-09-26Created from EPrint's last_modified field
- Caltech groups
- Richard N. Merkin Institute for Translational Research