Tuomas P. J. Knowles

Opposing Regulation of Tau Condensation by Phosphorylation Levels and Molecular Chaperone Interactions

This study investigates how phosphorylation levels and the molecular chaperone Bri2 BRICHOS opposingly regulate Tau condensation and aggregation, revealing their roles in tauopathies.

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.

Charge-driven remodelling of monomeric Tau determines its phase behaviour

This study shows that charge-driven conformational changes in Tau affect its phase behaviour and aggregation propensity.

Mechanistic Interpretability of Protein Language Models Reveals Encoded Structural and Functional Properties of Intrinsically Disordered Proteins

This study examines how protein language models handle intrinsically disordered proteins, finding they encode structural and functional information despite reduced attention on disordered regions.

Systematic identification of pH-sensing amyloid core motifs reveals a widespread mechanism for reversible protein assembly upon stress

The paper identifies pH-sensing amyloid core motifs in yeast and human proteomes, showing they enable reversible protein assembly under stress.

Errors in peptide synthesis are a source of discrepancies in Aβ42 studies

This study shows that sequence imperfections in synthetic Aβ42 peptides cause differences in aggregation behavior compared to recombinant Aβ42.

Complex coacervation reshapes the aggregation landscape of tau

This study shows that complex coacervation changes tau aggregation by redirecting it to a distinct kinetic regime and altering amyloid properties.

Mechanical Profiling of Biopolymer Condensates through Acoustic Trapping

This study uses acoustic trapping to measure the mechanical properties of single biopolymer condensates, showing it can detect changes in bulk modulus under different environmental conditions.

Mapping high resolution, multidimensional phase diagrams of physiological protein condensates

This study introduces ExVivo PhaseScan to generate high-resolution phase diagrams of physiological protein condensates and reveals how FUS mutations cause liquid-to-solid transitions in stress granules and nucleoli.

Many-body Interaction Competition Drives Reentrant Phase Transitions

This paper shows how introducing reversible dimerization into a Flory-Huggins model creates an effective three-body repulsion, explaining reentrant phase transitions in biomolecular condensates.

In vitro liquid-liquid phase separation induced by respiratory syncytial virus proteins and RNA

This study characterizes liquid-liquid phase separation driven by RSV proteins and RNA, identifying key interactions and stoichiometric requirements for condensate formation.

Nuclear Pct1 couples phosphatidylcholine synthesis with membrane biogenesis

The paper shows that Pct1, a nuclear enzyme in yeast, senses lipid imbalance and coordinates phosphatidylcholine synthesis with membrane biogenesis.

The role of N-terminal acetylation on biomolecular condensation

This study investigates how N-terminal acetylation affects biomolecular condensation using Grh1 in yeast, showing it alters condensate properties like size, stability, and structure.

Lipoengineering of Biomolecular Condensates Controls Material Properties and Multiphase Hierarchy to Guide Organoid Morphogenesis

This study uses lipidation to control biomolecular condensate properties and interactions, enabling the creation of multi-phase hydrogels that guide intestinal organoid morphogenesis.

Reversible peptide self-assembly enables sustained drug delivery with tuneable pharmacokinetics

This paper demonstrates that reversible peptide self-assembly can be used to achieve tuneable pharmacokinetics for therapeutic peptides, as shown with pramlintide in a rat model.

Structural defects in amyloid-β fibrils drive secondary nucleation

This study shows that structural defects in amyloid-β fibrils are key sites for secondary nucleation, suggesting new strategies for drug design to inhibit amyloid disorders.

Molecularly specific solubilization of therapeutic antibodies

The paper quantifies how different excipients affect the solubility of therapeutic antibodies using a high-throughput platform and identifies molecular-specific and nonspecific interactions.

Biomolecular condensates sustain pH gradients at equilibrium driven by charge neutralisation

This study shows that biomolecular condensates can sustain pH gradients without energy input by neutralizing charges, revealing their role in creating pH microenvironments.

Patch deconvolution for Fourier light-field microscopy

This paper introduces patch deconvolution to accelerate 3D cellular imaging in Fourier light-field microscopy, achieving faster reconstruction speeds without compromising quality.

Tau catalyzes amyloid-β aggregation in a fold-dependent manner

This study shows tau proteins from Alzheimer's and CTE folds catalyze Aβ42 aggregation in a fold-specific manner, increasing toxicity and offering new therapeutic insights.

Secondary nucleation of α-Synuclein drives Mitochondria dysfunctions and Lewy body formation in Parkinson's Disease

This study identifies secondary nucleation of α-Synuclein as the key mechanism driving mitochondrial dysfunction and Lewy body formation in Parkinson's Disease.

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.

Scaling relations of multi-component phase coexistence boundaries

This paper introduces a framework for quantitatively analyzing phase diagrams of multicomponent systems, revealing two scaling regimes for phase boundaries.

Im-seq: Multimodal droplet barcoding enables high-throughput linking of single-cell imaging and gene expression

The paper introduces a method to link single-cell imaging and gene expression data through multimodal droplet barcoding, identifying genes correlated with phenotypic features.

Dissecting the molecular origins of opalescence and phase separation in mAb formulations and their relation to aggregation

This paper investigates the molecular mechanisms of opalescence and liquid-liquid phase separation in mAb formulations and shows they are decoupled from aggregation.

Model Agnostic Conditioning of Boltzmann Generators for Peptide Cyclization

This paper introduces a model-agnostic framework to condition Boltzmann generators for sampling cyclic peptide conformations without retraining, using chemically informed loss functions and geometric constraints.

Diffusing protein binders to intrinsically disordered proteins

The paper develops RFdiffusion to generate protein binders for IDPs/IDRs, achieving nanomolar affinity and functional applications in amylin and IL2RG.

Global kinetic model of lipid-induced alpha-synuclein aggregation and its inhibition by small molecules

This paper develops a global kinetic model of lipid-induced alpha-synuclein aggregation and identifies how squalamine inhibits this process by reducing lipid-dependent primary nucleation.

DNA Partitioning Modulates Liquid-to-Solid Transitions and the Internal Microstructure of FUS Condensates

This study investigates how DNA partitioning affects the phase behavior and dynamics of FUS condensates, revealing its role in modulating liquid-to-solid transitions and microstructure over time.

Phosphorylation enables allosteric control of a viral condensate

This study shows that phosphorylation enables distinct nucleation mechanisms for NSP5 condensate formation in rotaviruses, depending on strain-specific LLPS propensity.