T. P. Knowles

Molecular mechanism of α-synuclein aggregation on lipid membranes revealed.

This study reveals that lipids promote α-synuclein aggregation by enabling elongation, using a kinetic model to describe the co-aggregation process in vitro.

α-Synuclein oligomers form by secondary nucleation

This study shows α-synuclein oligomers form via secondary nucleation on fibril surfaces, not from monomers, and this process is enhanced by agitation under physiological conditions.

ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes

This study shows ANXA11 biomolecular condensates couple protein and lipid phase states on lysosomal membranes through interactions with ALG2 and CALC.

Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions

The paper shows that proteins forming liquid condensates can reenter a phase-separated state at high salt concentrations due to hydrophobic and non-ionic interactions, distinct from low-salt electrostatic-driven phase separation.

Perphenazine-macrocycle conjugates rapidly sequester the Aβ42 monomer and inhibit amyloid formation

This study designs perphenazine-cyclam conjugates that bind Aβ42 monomers, reducing toxic oligomers and fibrils, and inhibit amyloid formation even with pre-formed seeds.

Amplification, not spreading limits rate of tau aggregate accumulation in Alzheimer's disease

The paper quantifies tau aggregate replication rates in Alzheimer's disease and finds local replication, not spreading, limits tau accumulation in neocortical regions.

Small molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer's disease

This paper identifies a small molecule that binds and sequesters monomeric amyloid-β, inhibiting its aggregation and rescuing toxicity in a C. elegans model.

High Resolution Biomolecular Condensate Phase Diagrams with a Combinatorial Microdroplet Platform

This paper introduces a microdroplet platform to rapidly generate high-resolution phase diagrams of biomolecular condensates and demonstrates its application in studying phase transitions.

Templating S100A9 amyloids on Aβ fibrillar surfaces revealed by charge detection mass spectrometry, microscopy, kinetic and microfluidic analyses

The paper investigates the co-aggregation of S100A9 and Aβ42 amyloids using CDMS, microscopy, and kinetic analysis, revealing templating of S100A9 fibrils on Aβ42 surfaces.

Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide

This study investigates the dynamics of Aβ42 oligomers during amyloid fibril formation, revealing that most oligomers dissociate into monomers rather than forming fibrils.

Rapid Fractionation and Characterisation of Alpha-Synuclein Oligomers in Solution

This study demonstrates microfluidic free-flow electrophoresis for rapidly separating and characterizing alpha-synuclein oligomers in solution.

Kinetic fingerprints differentiate anti-Aβ therapies

This study uses kinetic analysis and binding measurements to compare four anti-Aβ antibodies, showing aducanumab uniquely reduces Aβ oligomer flux.