Simon Alberti Group – RTG 3120 Biomolecular Condensates

Alberti and Hyman among Clarivate’s Highly Cited Researchers in 2025

Mohamad Almedawar — Thu, 13 Nov 2025 08:04:48 +0000

RTG 3120 PI’s have been among the most highly cited authors in 2025, according to Clarivate, with Hyman and Alberti leading the way “in the top 1% by citations for their field(s) and publication year in the Web of Science Core Collection”

See the press release by TU Dresden: https://tu-dresden.de/tu-dresden/newsportal/news/starkes-zeichen-fuer-die-qualitaet-der-spitzenforschung-13-forschende-der-tud-gehoeren-zu-den-meistzitierten-weltweit?set_language=en

See the full list: https://clarivate.com/highly-cited-researchers/

Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates

Mohamad Almedawar — Wed, 20 Aug 2025 13:15:24 +0000

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.

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

A role for RNA in Stress Granules assembly

snmadmin — Wed, 12 Jan 2022 10:05:03 +0000

Stress granules are membraneless compartments formed by phase separation of specific molecules upon exposure to cellular stress such as oxidative stress, heat shock, or osmotic stress.

The Alberti, Jahnel, Honigmann, and Hyman labs published a study in cell highlighting the role of RNA in the assembly of stress granules by crosslinkinig with G3BP clusters and how G3BP clusters in return prevent RNA entanglement. The study entitled “RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation” is in collaboration with Washington University, the European Molecular Biology Laboratory, Heidelberg, and Pohang University of Science and Technology, Korea.

Graphical Abstract:

Abstract:

Stressed cells shut down translation, release mRNA molecules from polysomes, and form stress granules (SGs) via a network of interactions that involve G3BP. Here we focus on the mechanistic underpinnings of SG assembly. We show that, under non-stress conditions, G3BP adopts a compact auto-inhibited state stabilized by electrostatic intramolecular interactions between the intrinsically disordered acidic tracts and the positively charged arginine-rich region. Upon release from polysomes, unfolded mRNAs outcompete G3BP auto-inhibitory interactions, engendering a conformational transition that facilitates clustering of G3BP through protein-RNA interactions. Subsequent physical crosslinking of G3BP clusters drives RNA molecules into networked RNA/protein condensates. We show that G3BP condensates impede RNA entanglement and recruit additional client proteins that promote SG maturation or induce a liquid-to-solid transition that may underlie disease. We propose that condensation coupled to conformational rearrangements and heterotypic multivalent interactions may be a general principle underlying RNP granule assembly.

Read the full publication

https://www.sciencedirect.com/science/article/pii/S0092867420303421

Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells

snmadmin — Mon, 10 Jan 2022 12:46:46 +0000

Aminoacyl-tRNA synthetases (aaRSs), the enzymes responsible for coupling tRNAs to their cognate amino acids, minimize translational errors by intrinsic hydrolytic editing. Here, we compared norvaline (Nva), a linear amino acid not coded for protein synthesis, to the proteinogenic, branched valine (Val) in their propensity to mistranslate isoleucine (Ile) in proteins. We show that in the synthetic site of isoleucyl-tRNA synthetase (IleRS), Nva and Val are activated and transferred to tRNA at similar rates. The efficiency of the synthetic site in pre-transfer editing of Nva and Val also appears to be similar. Post-transfer editing was, however, more rapid with Nva and consequently IleRS misaminoacylates Nva-tRNA^Ile at slower rate than Val-tRNA^Ile. Accordingly, an Escherichia coli strain lacking IleRS post-transfer editing misincorporated Nva and Val in the proteome to a similar extent and at the same Ile positions. However, Nva mistranslation inflicted higher toxicity than Val, in agreement with IleRS editing being optimized for hydrolysis of Nva-tRNA^Ile. Furthermore, we found that the evolutionary-related IleRS, leucyl- and valyl-tRNA synthetases (I/L/VRSs), all efficiently hydrolyze Nva-tRNAs even when editing of Nva seems redundant. We thus hypothesize that editing of Nva-tRNAs had already existed in the last common ancestor of I/L/VRSs, and that the editing domain of I/L/VRSs had primarily evolved to prevent infiltration of Nva into modern proteins.

Keywords: aminoacyl-tRNA synthetase; mistranslation; non-proteinogenic amino acids; primordial translation; proofreading.

Condensation regulates translation

snmadmin — Mon, 10 Jan 2022 12:45:57 +0000

New insights into the influence of Ded1p condensation on translation comes from the Hyman, Alberti and Kreysing labs. The study published in Cell is entitled “Condensation of Ded1p Promotes a Translational Switch from Housekeeping to Stress Protein Production”.

Graphical abstract:

Abstract:

Cells sense elevated temperatures and mount an adaptive heat shock response that involves changes in gene expression, but the underlying mechanisms, particularly on the level of translation, remain unknown. Here we report that, in budding yeast, the essential translation initiation factor Ded1p undergoes heat-induced phase separation into gel-like condensates. Using ribosome profiling and an in vitro translation assay, we reveal that condensate formation inactivates Ded1p and represses translation of housekeeping mRNAs while promoting translation of stress mRNAs. Testing a variant of Ded1p with altered phase behavior as well as Ded1p homologs from diverse species, we demonstrate that Ded1p condensation is adaptive and fine-tuned to the maximum growth temperature of the respective organism. We conclude that Ded1p condensation is an integral part of an extended heat shock response that selectively represses translation of housekeeping mRNAs to promote survival under conditions of severe heat stress.

Local nucleation of microtubule bundles through tubulin concentration into a condensed tau phase

snmadmin — Tue, 05 Sep 2017 07:51:22 +0000

Theskeleton that supports the structure of our cells, termed cytoskeleton is formed of several kinds of polymers including actin and microtubules. How the single units on the polymers (monomers and dimers) are concentrated to gether to synthesize the polymer is the subject of this study by the labs of Diez, Hyman, and Alberti. The authors identified a protein associated to the cytoskeleton, named Tau, that is able to phase-separate from the cytosol. Tau concentrates the tubulin dimers, which in turn polymerize to make microtubules inside the tau droplet. As opposed to this physiological phenomenon, pathological aggregation of mutated tau is a hallmark of neurodegenerative disorders, including Alzheimer’s disease.

Read more: https://doi.org/10.1016/j.celrep.2017.08.042