Simon Alberti
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View article: Quantifying collective interactions in biomolecular phase separation
Quantifying collective interactions in biomolecular phase separation Open
Biomolecular phase separation is an emerging theme for protein assembly and cellular organisation. The collective forces driving such condensation, however, remain challenging to characterise. Here we show that tracking the dilute phase co…
View article: Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates
Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates Open
Cytosolic aggregation of the nuclear protein TAR DNA-binding protein 43 (TDP-43) is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation re…
<span>SHARK</span>‐capture identifies functional motifs in intrinsically disordered protein regions Open
Increasing insights into how sequence motifs in intrinsically disordered regions (IDRs) provide functions underscore the need for systematic motif detection. Contrary to structured regions where motifs can be readily identified from sequen…
SUMO2/3 conjugation of TDP-43 protects against aggregation Open
Cytosolic aggregation of the RNA binding protein TDP-43 (transactive response DNA-binding protein 43) is a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that during oxidative stress, TDP-43 becomes …
View article: Molecular determinants of condensate composition
Molecular determinants of condensate composition Open
Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the…
G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability Open
Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly and regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with u…
View article: Optical characterization of molecular interaction strength in protein condensates
Optical characterization of molecular interaction strength in protein condensates Open
Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular in…
Surviving the heat: the role of macromolecular assemblies in promoting cellular shutdown Open
During heat shock (HS), cells orchestrate a gene expression program that promotes the synthesis of HS proteins (HSPs) while simultaneously repressing the synthesis of other proteins, including growth-promoting housekeeping proteins. Recent…
View article: Single-molecule digital sizing of proteins in solution
Single-molecule digital sizing of proteins in solution Open
The physical characterization of proteins in terms of their sizes, interactions, and assembly states is key to understanding their biological function and dysfunction. However, this has remained a difficult task because proteins are often …
View article: Post-transcriptional regulation of insulin mRNA storage by G3BP1/2<sup>+</sup>condensates in beta cells
Post-transcriptional regulation of insulin mRNA storage by G3BP1/2<sup>+</sup>condensates in beta cells Open
Hyperglycemia upregulates insulin translation in pancreatic beta cells. Several RNA- binding proteins involved in this process have been identified, including G3BP1, a stress granule marker downregulated in islets of subjects with type 2 d…
View article: Biomolecular condensates sustain pH gradients at equilibrium through charge neutralisation
Biomolecular condensates sustain pH gradients at equilibrium through charge neutralisation Open
Electrochemical gradients are essential to the functioning of cells and form across membranes using active transporters. Here, we show in contrast that condensed biomolecular systems sustain significant pH gradients without any external en…
eIF4F is a thermo-sensing regulatory node in the translational heat shock response Open
Heat-shocked cells prioritize the translation of heat shock (HS) mRNAs, but the underlying mechanism is unclear. We report that HS in budding yeast induces the disassembly of the eIF4F complex, where eIF4G and eIF4E assemble into translati…
View article: Optical characterization of molecular interaction strength in protein condensates
Optical characterization of molecular interaction strength in protein condensates Open
Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular in…
View article: Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system
Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system Open
The Integrated Stress Response Inhibitor (ISRIB) is an experimental compound that has been used to explore the potential beneficial effects of reducing the activation of the integrated stress response (ISR). As the ISR is a protective resp…
View article: PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends
PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends Open
DNA double-strand breaks (DSBs) are repaired at DSB sites. How DSB sites assemble and how broken DNA is prevented from separating is not understood. Here we uncover that the synapsis of broken DNA is mediated by the DSB sensor protein poly…
View article: Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates
Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates Open
SUMMARY Cytosolic aggregation of the nuclear protein TDP-43 is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event…
View article: Single-molecule digital sizing of proteins in solution
Single-molecule digital sizing of proteins in solution Open
Proteins constitute the molecular machinery of life and exert their biological function by interacting with other proteins, as well as by assembling into biomolecular complexes and higher order structures. Characterizing the sizes, interac…
View article: Human Small Heat Shock Protein B8 Inhibits Protein Aggregation without Affecting the Native Folding Process
Human Small Heat Shock Protein B8 Inhibits Protein Aggregation without Affecting the Native Folding Process Open
Small Heat Shock Proteins (sHSPs) are key components of our Protein Quality Control system and are thought to act as reservoirs that neutralize irreversible protein aggregation. Yet, sHSPs can also act as sequestrases, promoting protein se…
View article: Quantifying collective interactions in biomolecular phase separation
Quantifying collective interactions in biomolecular phase separation Open
Biomolecular phase separation plays a pivotal role in governing critical biological functions and arises from the collective interactions of large numbers of molecules. Characterising the underlying collective interactions of phase separat…
View article: Direct digital sensing of protein biomarkers in solution
Direct digital sensing of protein biomarkers in solution Open
The detection of proteins is of central importance to biomolecular analysis and diagnostics. Typical immunosensing assays rely on surface-capture of target molecules, but this constraint can limit specificity, sensitivity, and the ability …
View article: Direct digital sensing of protein biomarkers in solution.
Direct digital sensing of protein biomarkers in solution. Open
The detection of proteins is of central importance to biomolecular analysis and diagnostics. Typical immunosensing assays rely on surface-capture of target molecules, but this constraint can limit specificity, sensitivity, and the ability …