Randal Halfmann

Eukaryotic domestication of a TIR bacterial immune protein following horizontal transfer

This study identifies a horizontal transfer of a bacterial TIR immune protein to amoebae, showing how it was domesticated into eukaryotic physiology through functional adaptation.

State-selective inhibition of alpha-synuclein aggregation by de novo oligomer-binding proteins

This study designs de novo proteins that selectively inhibit alpha-synuclein aggregation by targeting specific intermediates, with one binder preferentially inhibiting oligomer formation and secondary nucleation.

Simulation of cell-size systems at long timescales with flexible protein structures

The paper introduces a docking-based simulation method that combines rigid-body approximations with flexible protein structures to model macromolecular interactions in crowded cellular environments over long timescales.

Nascent protein retention at polysomes reduces kinetic barriers to self-assembly

The paper shows that increasing translation initiation rates accelerates nucleation of aggregating proteins at polysomes, suggesting cotranslational nucleation influences proteome evolution.

Intracellular TDP-43 amyloid nucleates from arrested nascent condensates

This study shows TDP-43 amyloid forms only when its C-terminal domain arrests in soluble clusters, and this process can be inhibited by co-expressing an oligomeric binder.

Neurodegeneration emerges at a cellular tipping point between aggregate accumulation and removal.

The paper identifies a cellular tipping point between aggregate accumulation and removal as a universal feature of neurodegeneration, validated through live-cell assays and super-resolution imaging.

A tool to dissect heterotypic determinants of homotypic protein phase behavior

The paper introduces a tool to study how modifier proteins affect the phase behavior of query proteins through controlled interaction modulation.

Bottom-up reconstruction of functional Death Domain Signalosomes reveals a requirement for polymer stability and avidity

The paper constructs a synthetic signalosome using Death Domains and shows that its function depends on polymer stability and avidity, demonstrating these properties are tunable and not restricted to specific motifs.

Functional constraints of wtf killer meiotic drivers

This study investigates the molecular mechanisms of wtf killer meiotic drivers in fission yeasts, identifying factors that constrain toxicity and neutralization, and suggests potential roles in infertility.

A tunable affinity fusion tag for protein self-assembly

This paper introduces a tunable amyloid-based fusion tag that allows precise control of protein concentration thresholds in cells.

Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal

This study identifies the structural basis of polyglutamine nucleation, showing that a four-stranded steric zipper initiates aggregation and poisons further growth.

Predicting interchain contacts for homodimeric and homomultimeric protein complexes using multiple sequence alignments of monomers and deep learning

The paper uses deep learning on monomeric multiple sequence alignments to predict interchain contacts in homomultimeric proteins, achieving high precision in some cases.