A. S. Holehouse

Disordered proteins interact with the chemical environment to tune their protective function during drying

This study investigates how disordered proteins interact with endogenous cosolutes during drying to enhance desiccation protection across different organisms.

Rational design of disordered proteins for systematic sequence-to-function investigation

This paper introduces GOOSE, a computational framework for designing intrinsically disordered proteins, and demonstrates its ability to create IDRs with specific functional responses.

Conserved molecular recognition by an intrinsically disordered region in the absence of sequence conservation

The paper investigates how sequence variation in intrinsically disordered regions (IDRs) can still encode functional specificity in RNA binding, using coronavirus nucleocapsid proteins as a model.

Helicity of a tardigrade disordered protein promotes desiccation tolerance

This study shows that helical structure in a tardigrade IDP is necessary for desiccation tolerance, but not sufficient on its own.

Labile assembly of a tardigrade protein induces biostasis

This study identifies a mechanism by which tardigrade CAHS D proteins form gels to protect cells during desiccation, showing that gelation reduces molecular motion and metabolic activity, with reversible effects.

Direct prediction of intrinsically disordered protein conformational properties from sequence

This paper develops ALBATROSS, a deep learning model that predicts ensemble conformational properties of intrinsically disordered proteins from sequence, enabling proteome-wide analysis.

FIREBALL: A tool to fit protein phase diagrams based on mean-field theories for polymer solutions

FIREBALL fits protein phase diagrams using mean-field theories to analyze phase separation parameters from experimental or computed data.

The analytical Flory random coil is a simple-to-use reference model for unfolded and disordered proteins

The paper introduces the analytical Flory Random Coil (AFRC) model as a reference for unfolded proteins, enabling comparison of experimental and simulation data.

Aberrant phase separation is a common killing strategy of positively charged peptides in biology and human disease

The paper identifies a common toxic mechanism in positively charged peptides across species and develops a machine learning tool to detect it.

SOURSOP: A Python package for the analysis of simulations of intrinsically disordered proteins

SOURSOP is a Python package for analyzing simulated conformational ensembles of intrinsically disordered proteins, offering tools to quantify sequence-specific properties.

The disordered N-terminal tail of SARS CoV-2 Nucleocapsid protein forms a dynamic complex with RNA

This study investigates how the disordered N-terminal tail of the SARS-CoV-2 Nucleocapsid protein enhances RNA binding affinity and modulates interactions with RNA.

A condensate forming tether for lariat debranching enzyme is defective in non-photosensitive trichiothiodystrophy

This study identifies TTDN1's role in linking intron lariat processing to the spliceosome, showing its defect causes splicing and gene expression issues in NP-TTD.

The kinetic landscape of human transcription factors

This study develops CRISPRburst to measure how 92 human transcription factors affect transcriptional bursting kinetics and identifies kinetic signatures that classify TFs and predict their regulatory roles.

Composition can buffer protein dynamics within liquid-like condensates.

The paper shows that adding other components to liquid-like condensates can stabilize protein dynamics, mediated by weak interactions among multiple components.

Sequence- and chemical specificity define the functional landscape of intrinsically disordered regions

The paper investigates how sequence- and chemical specificity enable functional IDR diversity despite poor sequence conservation.

Structural biases in disordered proteins are prevalent in the cell

The paper shows that structural biases in intrinsically disordered proteins persist in human cells and can respond to intracellular changes.

Tardigrade CAHS Proteins Act as Molecular Swiss Army Knives to Mediate Desiccation Tolerance Through Multiple Mechanisms

This study identifies CAHS D as a tardigrade protein that protects against desiccation through multiple mechanisms involving water coordination and slowed molecular motion.

Conformational buffering underlies functional selection in intrinsically disordered protein regions

The paper identifies conformational buffering as a mechanism that conserves spatial dimensions in disordered protein regions despite sequence variation, enabling functional selection.

Shelterin components modulate nucleic acids condensation and phase separation in the context of telomeric DNA

The paper shows TRF2 drives single telomere condensation and multi-telomere phase separation, with hRap1 modulating these processes.

Sequence determinants of in cell condensate assembly morphology, dynamics, and oligomerization as measured by number and brightness analysis

This study uses number and brightness analysis to examine how IDR amino acid composition affects ARF19 condensate morphology and material properties, but not oligomeric state.

The arrested state of processing bodies supports mRNA regulation in early development

This study shows that arrested P body condensates in Drosophila oocytes prevent premature mRNA release, supporting mRNA regulation during early development.

A modular platform for engineering function ofnatural and synthetic biomolecular condensates

The paper identifies design principles for biomolecular condensates using PopZ and applies them to create synthetic condensates in human cells.

SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation

This study identifies cholesterol's essential role in SARS-CoV-2 membrane fusion and syncytia formation, suggesting statins may benefit COVID-19 patients.

Probing the Hidden Sensitivity of Intrinsically Disordered Proteins to their Chemical Environment

This study develops a framework to characterize how intrinsically disordered proteins (IDRs) respond to their chemical environment, finding sequence-dependent sensitivity and potential regulatory roles.

Hydration-dependent phase separation of a prion-like protein regulates seed germination during water stress.

This study identifies FLOE1, a prion-like protein in Arabidopsis thaliana, whose hydration-dependent phase separation regulates seed germination under water stress.

The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA

This study investigates the SARS-CoV-2 nucleocapsid protein's dynamics, disorder, and RNA phase separation using single-molecule spectroscopy and simulations, revealing its multivalent RNA binding properties and phase separation behavior.

Connecting coil-to-globule transitions to full phase diagrams for intrinsically disordered proteins

The paper introduces a computational approach to predict sequence-specific phase diagrams for intrinsically disordered proteins by combining simulations with Gaussian cluster theory.

Insights from a survey-based analysis of the academic job market

This study analyzes survey data from faculty job applicants to assess how various metrics correlate with hiring outcomes and highlights issues with the academic job application process.

Protein products of non-stop mRNA disrupt nucleolar homeostasis

This study shows that nonstop mRNA proteins accumulate in nucleoli, disrupting their structure and function, and links this to neurodegeneration mechanisms.

Arginine-enriched mixed-charge domains provide cohesion for nuclear speckle condensation

The paper identifies sequence features of mixed-charge domains that govern nuclear speckle condensation and function in mRNA processing.