2025 – RTG 3120 Biomolecular Condensates https://dresdencondensates.org From Physics to Biological Functions Thu, 11 Sep 2025 13:01:15 +0000 en-US hourly 1 https://wordpress.org/?v=6.9.4 https://dresdencondensates.org/wp-content/uploads/2022/01/cropped-Icon-32x32.jpg 2025 – RTG 3120 Biomolecular Condensates https://dresdencondensates.org 32 32 Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates https://dresdencondensates.org/intra-condensate-demixing-of-tdp-43-inside-stress-granules-generates-pathological-aggregates/ https://dresdencondensates.org/intra-condensate-demixing-of-tdp-43-inside-stress-granules-generates-pathological-aggregates/#respond Wed, 20 Aug 2025 13:15:24 +0000 https://dresdencondensates.org/?p=1946 A new study from the labs of Honigmann, Hyman, and Alberti in Dresden, in addition to colleagues in Texas A&M University, Mayo Clinic, Brown University, and Saint Louis University investigates the mechanism behind pathological outcomes of protein aggregation inside stress granules. The authors of the study entitled “Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates” and published in Cell in May, 2025, determined that aggregation of TAR DNA-binding protein 43 (TDP-43) is induced by two events, namely up-concentration of TDP-43 in stress granules beyond a threshold and oxidative stress and described the mechanism behind the observation. They use this new understanding to engineer TDP-43 variants resistant to aggregation in the cell.

Impact: The aggregation of TDP-43 in motor neurons  is a hallmark of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Understanding the mechanisms leading to aggregation paves the path towards developing preventive and therapeutic strategies.

Graphical Abstract to paper 'Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates'
© 2025 The Author(s). Published by Elsevier Inc.

Citation:

Yan, X., Kuster, D., Mohanty, P., Nijssen, J., Pombo-García, K., Garcia Morato, J., Rizuan, A., Franzmann, T. M., Sergeeva, A., Ly, A. M., Liu, F., Passos, P. M., George, L., Wang, S.-H., Shenoy, J., Danielson, H. L., Ozguney, B., Honigmann, A., Ayala, Y. M., Fawzi, N. L., Dickson, D. W., Rossoll, W., Mittal, J., Alberti, S., & Hyman, A. A. (2025). Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates. Cell, 188(15), 4123-4140.e4118. https://doi.org/10.1016/j.cell.2025.04.039

]]> https://dresdencondensates.org/intra-condensate-demixing-of-tdp-43-inside-stress-granules-generates-pathological-aggregates/feed/ 0 Impact of Coiled-Coil Domains on the Phase Behavior of Biomolecular Condensates https://dresdencondensates.org/impact-of-coiled-coil-domains-on-the-phase-behavior-of-biomolecular-condensates/ https://dresdencondensates.org/impact-of-coiled-coil-domains-on-the-phase-behavior-of-biomolecular-condensates/#respond Wed, 20 Aug 2025 12:35:44 +0000 https://dresdencondensates.org/?p=1942 A new Study from the Harmon and Sommer Labs in ACS Macro Letters entitled ‘Impact of Coiled-Coil Domains on the Phase Behavior of Biomolecular Condensates’ addressed how the geometry and structure of folded domains impact condensate formation. They used coarse-grained simulations to determine that coiled-coil domains (CCDs) promote liquid–liquid phase separation (LLPS), while replacing the CCD with a flexible linker abolishes LLPS. CCDs must have a critical length to promote LLPS at low concentrations.

The results of this study offer a framework for designing synthetic condensates with tunable phase behaviors.

Figure for paper "Impact of Coiled-Coil Domains on the Phase Behavior of Biomolecular Condensates"
© 2025 American Chemical Society

Citation:

Zhouyi He, Jens-Uwe Sommer, and Tyler S. Harmon. Impact of Coiled-Coil Domains on the Phase Behavior of Biomolecular Condensates. ACS Macro Letters 2025 14 (4), 413-419. DOI: 10.1021/acsmacrolett.4c00821

 

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