Tuomas P. J. Knowles

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

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.

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

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

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

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

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

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.

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.

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.

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

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

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

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

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.

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.

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

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

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

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.

This study characterizes the aging behavior of FUS condensates using microfluidic technology and surface-based techniques, revealing phase transitions and structural changes associated with material properties.

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

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.

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

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

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

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.

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

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.

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.