A5050655274- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Prion Diseases and Protein Misfolding
- Supramolecular Self-Assembly in Materials
- Machine Learning in Bioinformatics
- Pickering emulsions and particle stabilization
- Enzyme Structure and Function
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Bioinformatics and Genomic Networks
- Lipid Membrane Structure and Behavior
- Advanced Neuroimaging Techniques and Applications
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Field-Flow Fractionation Techniques
- ATP Synthase and ATPases Research
- Connective tissue disorders research
University of Leeds
2023-2025
Institute of Structural and Molecular Biology
2023-2025
University of Kent
2020-2023
University of Sheffield
2022
α-, β-, and γ-Synuclein are intrinsically disordered proteins implicated in physiological processes the nervous system of vertebrates. α-synuclein (αSyn) is amyloidogenic protein associated with Parkinson’s disease certain other neurodegenerative disorders. Intensive research has focused on mechanisms that cause αSyn to form amyloid structures, identifying its NAC region as being necessary sufficient for assembly. Recent work shown a 7-residue sequence (P1) formation. Although γ-synuclein...
Significance The formation of disease-associated fibrillar amyloid structures can be accelerated by preformed seeds. This seeding process is thought to occur solely through elongation at fibril ends, resulting in the templated propagation protein conformation encoded We demonstrate that does not always proceed and show seeds are nanoparticles accelerate new heterologous without templating provide experimentally testable criteria distinguish a mechanism from surface catalysis present...
β2-microglobulin (β2m) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils the joints, causing disorder dialysis-related amyloidosis (DRA). Point mutations of β2m result diseases with distinct pathologies. β2m-D76N causes a rare systemic protein deposited viscera absence renal failure, whilst β2m-V27M is associated deposits forming predominantly tongue. Here we use cryoEM to determine structures formed from these variants under identical conditions vitro. We show that each...
Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism not understood due to lack structural insights at the single-fibril level. To identify and classify fibril polymorphs quantify level heterogeneity is essential decipher precise links between their functional disease associated properties such as toxicity, strains,...
Abstract Structural polymorphism has been demonstrated for both in vitro and ex vivo amyloid fibrils associated with disease. The manner which different filament structures are assembled from common building blocks remains unclear but the assembly environment is likely to be a key determinant. To address this, three-dimensional reconstruction of individual was conducted atomic force microscopy images map structural landscape Aβ 42 fibril populations formed under most frequently used buffer...
Self-assembly of the amyloid-β (Aβ) peptide to form toxic oligomers and fibrils is a key causal event in onset Alzheimer's disease, Aβ focus intense research neuroscience, biophysics, structural biology aimed at therapeutic development. Due its rapid self-assembly extreme sensitivity aggregation conditions, preparation seedless, reproducible solutions highly challenging, there are serious ongoing issues with consistency literature. In this paper, we use liquid-phase separation technique,...
ABSTRACT Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism not understood due to lack structural insights at the single-fibril level. To identify and classify fibril polymorphs quantify level heterogeneity is essential decipher precise links between their functional disease associated properties such as toxicity,...
Abstract It is still unclear why pathological amyloid deposition initiates in specific brain regions, nor cells or tissues are more susceptible than others. Amyloid determined by the self-assembly of short protein segments called aggregation-prone regions (APRs) that favour cross-β structure. Here we investigated whether Aβ assembly can be modified heterotypic interactions between APRs and homologous otherwise unrelated human proteins. We identified accelerate assembly, modify fibril...