D. M. Hatters

Replicative aging impedes stress-induced assembly of a key human protein disaggregase

This study identifies a stress-induced trimeric protein disaggregase in human cells that collapses during replicative aging, contributing to pathophysiological consequences.

Protein painting reveals pervasive remodeling of conserved proteostasis machinery in response to pharmacological stimuli.

The paper uses protein painting to show how pharmacological stimuli remodel conserved proteostasis machinery across the proteome in whole cells.

Arginine-rich C9ORF72 ALS proteins stall ribosomes in a manner distinct from a canonical ribosome-associated quality control substrate

The paper investigates how arginine-rich DPRs from C9ORF72 expansions stall ribosomes and shows that this stalling differs from canonical RQC substrates, with no natural regulatory responses.

Sequence grammar underlying unfolding and phase separation of globular proteins

The paper investigates how sequence grammars of unfolded globular proteins drive phase separation and formation of UPODs, highlighting the role of hydrophobic residues and their impact on disease-related interactions.

A biosensor to gauge protein homeostasis resilience differences in the nucleus compared to cytosol of mammalian cells

The paper develops a biosensor to compare protein homeostasis resilience in the nucleus and cytosol of human cells, finding the nucleus has lower chaperone activity and aggregation suppression capacity.

Hidden information on protein function in censuses of proteome foldedness

The paper shows proteome folding stability censuses are unreliable due to hidden information on conformation and ligand binding.

Nascent mutant Huntingtin exon 1 chains do not stall on ribosomes during translation but aggregates do recruit machinery involved in ribosome quality control

This study investigates how mutant Huntingtin exon 1 chains form inclusions in cells, finding that nascent chains do not stall on ribosomes but that ribosome quality control proteins are recruited into the aggregates.

Inclusion bodies formed by polyglutamine and poly(glycine-alanine) are enriched with distinct proteomes but converge in proteins that are risk factors for disease and involved in protein degradation

The paper compares proteomes enriched in polyGA and polyQ inclusion bodies, finding distinct protein sets but shared degradation-related proteins linked to neurodegenerative diseases.

Arginine valency in C9ORF72 dipolypeptides mediates promiscuous proteome binding that stalls ribosomes, disable actin cytoskeleton assembly and impairs arginine methylation of endogenous proteins

This study shows that arginine valency in C9ORF72 DPRs causes promiscuous proteome binding, ribosome stalling, actin cytoskeleton disruption, and arginine hypomethylation.

Widespread remodelling of proteome solubility in response to different protein homeostasis stresses

The paper measures proteome solubility changes in Neuro2a cells under various protein homeostasis stresses and finds widespread remodelling with specific patterns of solubility shifts.

Tadpole-like conformations of huntingtin exon 1 with expanded polyglutamine engenders novel interactions in cells

The paper investigates the structure of Httex1 with expanded polyQ and finds that its tadpole-like conformation increases interactions in cells, potentially contributing to neurotoxicity.