A5068851610- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Prion Diseases and Protein Misfolding
- Enzyme Structure and Function
- Supramolecular Self-Assembly in Materials
- Lipid Membrane Structure and Behavior
- Force Microscopy Techniques and Applications
- Advanced Neuroimaging Techniques and Applications
- Viral gastroenteritis research and epidemiology
- Advanced biosensing and bioanalysis techniques
- Ionic liquids properties and applications
- Parkinson's Disease Mechanisms and Treatments
- Bacterial Genetics and Biotechnology
- Amyloidosis: Diagnosis, Treatment, Outcomes
- NMR spectroscopy and applications
- Computational Drug Discovery Methods
- Amoebic Infections and Treatments
- Pharmaceutical and Antibiotic Environmental Impacts
- Parasitic Infections and Diagnostics
- Coal Properties and Utilization
- Nanocluster Synthesis and Applications
- Rock Mechanics and Modeling
- Trace Elements in Health
- S100 Proteins and Annexins
- Toxic Organic Pollutants Impact
University of Kent
2016-2025
Shaanxi Coal Chemical Industry Technology Research Institute
2022-2025
Xi'an University of Science and Technology
2022
Institut national de recherche en informatique et en automatique
2018-2021
Guangzhou Academy of Fine Arts
2020
Entry Exit Inspection and Quarantine Bureau
2017
Dalian University of Technology
2014-2016
University of Leeds
2007-2014
Kent and Canterbury Hospital
2014
Institute of Structural and Molecular Biology
2007-2013
Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing lag time for nucleation. Protein is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, dialysis-related amyloidosis. Fibril formation occurs nucleation-dependent kinetics, wherein a critical nucleus key rate-determining step, after which proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide quantum dots, carbon...
Self-assembly of misfolded proteins into ordered fibrillar aggregates known as amyloid results in numerous human diseases. Despite an increasing number and peptide fragments being recognised amyloidogenic, how these assemble remains unclear. In particular, the identity nucleating species, ephemeral entity that defines rate fibril formation, a key outstanding question. Here, we propose new strategy for analyzing self-assembly fibrils involving global analysis large reaction progress curves...
Fibrils associated with amyloid disease are molecular assemblies of key biological importance, yet how cells respond to the presence remains unclear. Cellular responses may not only depend on chemical composition or properties fibrils, but their physical attributes such as length, width, surface area also play important roles. Here, we report a systematic investigation effect fragmentation structural and fibrils. In addition expected relationship between ability seed, show striking finding...
Protein misfolding and aggregation cause serious degenerative conditions such as Alzheimer’s, Parkinson, prion diseases. Damage to membranes is thought be one of the mechanisms underlying cellular toxicity a range amyloid assemblies. Previous studies have indicated that fibrils can membrane leakage elicit damage, these effects are enhanced by fragmentation fibrils. Here we report direct 3D visualization damage specific interactions lipid bilayer with amyloid-like formed in vitro from β 2...
Targeting of proteins to bacterial microcompartments (BMCs) is mediated by an 18-amino-acid peptide sequence. Herein, we report the solution structure N-terminal targeting (P18) PduP, aldehyde dehydrogenase associated with 1,2-propanediol utilization metabolosome from Citrobacter freundii. The reveals have a well-defined helical conformation along its whole length. Saturation transfer difference and transferred NOE NMR has highlighted observed interaction surface on main interacting shell...
Amyloid assemblies are associated with several debilitating human disorders. Understanding the intra- and extracellular assembly of normally soluble proteins peptides into amyloid aggregates how they disrupt normal cellular functions is therefore paramount importance. In a recent report, we demonstrated striking relationship between reduced fibril length caused by fragmentation enhanced ability samples to membranes reduce cell viability. These findings have important implications for our...
Abstract Parkinson’s disease (PD) is characterized by intracellular, insoluble Lewy bodies composed of highly stable α-synuclein (α-syn) amyloid fibrils. an intrinsically disordered protein that has the capacity to assemble form β-sheet rich Oxidiative stress and metal environments have been implicated in triggering assembly. Here, we explored composition post-mortem tissue using electron microscopy immunogold labeling revealed dityrosine crosslinks brain from PD patients. In vitro , show...
The constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimer’s disease (AD) and other tauopathies. Full‐length tau requires addition anionic cofactors such as heparin enhance assembly. We have shown that a fragment from proteolytically stable core PHF, 297‐391 known ‘dGAE’, spontaneously forms cross‐β‐containing PHFs straight under physiological conditions. Here, we analysed compared structures formed...
The presence of amyloid fibrils is a hallmark more than 50 human disorders, including neurodegenerative diseases and systemic amyloidoses. A key unresolved challenge in understanding the involvement disease to explain relationship between individual structural polymorphs fibrils, potentially mixed populations, specific pathologies with which they are associated. Although cryo-electron microscopy (cryo-EM) solid-state nuclear magnetic resonance (ssNMR) spectroscopy methods have been...
The sequence VQIVYK is an aggregation prone region of the tau protein implicated in driving assembly into paired helical filaments. These filaments accumulate as intraneuronal neurofibrillary tangles Alzheimers disease and a range tauopathies. Here, we demonstrate that forms highly ordered fibrillar samples after prolonged incubation at room temperature. Remarkably, aligned fibre bundles give rise to unusually detailed oriented X-ray diffraction patterns. Analysis these patterns provide...
Delineating the nanoscale properties and dynamic assembly disassembly behaviors of amyloid fibrils is key for technological applications that use material fibrils, as well developing treatments amyloid-associated disease. However, quantitative mechanistic understanding complex processes involving these heterogeneous supramolecular systems presents challenges have yet to be resolved. Here, we develop an approach capable resolving time dependence fibril particle concentration, length...
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...
Coal, as an unconventional reservoir, is characterized by the development of micro/nano-meter pores and significant pore differences in different bedding directions. Pore heterogeneity anisotropy are key factors contributing to difference reservoir properties. This not only affects recovery resources but also interpretation seismic data. Currently, research on coal mainly focuses distribution. Nonetheless, there few studies a lack comprehensive knowledge regarding connectivity within same...
Abstract Tau undergoes fibrillogenesis in a group of neurodegenerative diseases termed tauopathies. Each tauopathy is characterized by tau fibrils with disease-specific conformations, highlighting the complexity self-assembly. This has led to debate surrounding precise mechanisms that govern self-assembly disease, especially involvement disulphide bonding (DSB) between cysteine residues. In this study, we use truncated form tau, dGAE, capable forming filaments identical those disease. We...
Amyloid fibrils are proteinaceous nano-scale linear aggregates. They of key interest not only because their association with numerous disorders, such as type II diabetes mellitus, Alzheimer's and Parkinson's diseases, but also potential to become engineered high-performance nano-materials. Methods characterise the length distribution aggregates amyloid paramount importance both in understanding biological impact these controlling mechanical properties Here, we present a new quantitative...
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,...
Although the molecular mechanisms underlying pathology of amyloidoses are not well understood, interaction between amyloid proteins and cell membranes is thought to play a role in several diseases. Amyloid fibrils β2-microglobulin (β2m), associated with dialysis-related amyloidosis (DRA), have been shown cause disruption anionic lipid bilayers vitro. However, effect composition chemical environment which β2m-lipid interactions occur investigated previously. Here we examine membrane damage...
Transmissible amyloid particles called prions are associated with infectious prion diseases in mammals and inherited phenotypes yeast. All aggregates can give rise to potentially seeds that accelerate their growth. Why some highly while others less or even inert, is currently not understood. To address this question, we analyzed the suprastructure dimensions of synthetic fibrils assembled from yeast (Saccharomyces cerevisiae) protein Sup35NM. We then quantified ability these induce [PSI+]...