A5090617480- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Parkinson's Disease Mechanisms and Treatments
- Electrochemical Analysis and Applications
- Supramolecular Self-Assembly in Materials
- Neuroscience and Neural Engineering
- Crystallization and Solubility Studies
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Erythrocyte Function and Pathophysiology
- Chemical Synthesis and Analysis
- Cellular Mechanics and Interactions
- Machine Learning in Bioinformatics
- RNA and protein synthesis mechanisms
- Chemical Thermodynamics and Molecular Structure
- Electrochemical sensors and biosensors
- Computational Drug Discovery Methods
- Advanced Fluorescence Microscopy Techniques
- Receptor Mechanisms and Signaling
- Spectroscopy and Quantum Chemical Studies
- Crystallography and molecular interactions
- Advancements in Battery Materials
- Digital Holography and Microscopy
- Cell Image Analysis Techniques
University of Limerick
2017-2025
Science Foundation Ireland
2022-2023
University of Cincinnati
2013
Lithium (Li) metal batteries (LMBs) provide superior energy densities far beyond current Li-ion (LIBs) but practical applications are hindered by uncontrolled dendrite formation and the build-up of dead Li in "hostless" anodes. To circumvent these issues, we created a 3D framework carbon paper (CP) substrate decorated with lithiophilic nanowires (silicon (Si), germanium (Ge), SiGe alloy NWs) that provides robust host for efficient stripping/plating metal. The Li22 Si5 , (Si0.5 Ge0.5 )5, Ge5...
Metal ions stabilize protein–protein interactions and can modulate protein aggregation. Here, using liquid-based atomic force microscopy molecular dynamics simulations, we study the concentration-dependent effect of Cu2+ on aggregation pathway α-synuclein (α-Syn) proteins, which play a key role in pathology Parkinson's disease. The full spectrum α-Syn aggregates presence absence from monomers to mature fibrils was resolved quantified at gold–water interface. Raman spectroscopy confirmed...
<title>Abstract</title> The preparation of new metallodrugs targeting DNA is key therapeutic interest. Recently, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click chemistry" reaction has emerged as a promising approach for designing artificial metallo-nucleases (AMNs) with DNA-damaging properties. By functionalising central organic azide three alkyne donors, Tri-Click (TC) ligands capable chelating copper ions through donor group and triazole linker can be generated. However,...
The presence of partially structured helices in natively unfolded amyloid-β42 (Aβ42) and α-synuclein (αS) has been shown to accelerate fibrillation the onset Alzheimer's Parkinson's disease, respectively. At other extreme, folded stable helical conformers have also reported resist amyloid formation. Recent studies indicate that amyloidogenic aggregation can be impeded using small molecules stabilize α-helical monomers switch off neurotoxic pathway. We predict a common intrapeptide route...
Protein fibril surfaces tend to generate toxic oligomers catalytically. To date, efforts study the accelerated aggregation steps involved with Alzheimer's disease-linked amyloid-β (Aβ)-42 proteins on have mainly relied fluorophore-based analytics. Here, we visualize rare secondary nucleation events surface of Aβ-42 fibrils from embryonic endpoint stages using liquid-based atomic force microscopy. Nanoscale imaging supported by atomic-scale molecular simulations tracked adsorption and...
The heterogeneity of the synucleinopathies, neurological disorders that include Parkinson's disease (PD), indicates toxicity, seeding/cross-seeding ability, and propagation α-synuclein (αS) assemblies depend on their distinct structural characteristics or "strain". To examine molecular signature encodes aggregation seed, conformational preference, thermodynamic stability full-length αS fibrils, we performed dynamics simulations two non-amyloid-β component (NAC) fibril structures, containing...
The potential of ultra-short peptides to self-assemble into well-ordered functional nanostructures makes them promising minimal components for mimicking the basic ingredient nature and diverse biomaterials. However, selection modular design perfect de novo sequences are extremely tricky due their vast possible combinatorial space. Moreover, a single amino acid substitution can drastically alter supramolecular packing structure short peptide assemblies. Here, we report rigid hybrid hydrogels...
Abstract Homochirality is a fundamental feature of all known forms life, maintaining biomolecules (amino-acids, proteins, sugars, nucleic acids) in one specific chiral form. While this condition central to biology, the mechanisms by which adverse accumulation non- l- α-amino-acids proteins lead pathophysiological consequences remain poorly understood. To address how heterochirality build-up impacts organism’s health, we use chiral-selective vivo assays detect protein-bound non -l -α-amino...
Understanding the dose-dependent effect of over-the-counter drugs on red blood cells (RBCs) is crucial for hematology and digital pathology. Yet, it challenging to continuously record real-time, drug-induced shape changes RBCs in a label-free manner. Here, we demonstrate holotomography (DHTM)-enabled concentration-dependent time-dependent monitoring ibuprofen from healthy donor. The are segmented based three-dimensional (3D) four-dimensional (4D) refractive index tomograms, their...
Polymorphism can be a valuable tool as well an impediment in the development and approval of pharmaceuticals, providing opportunity to tune active pharmaceutical ingredient (API) physicochemical properties. The control polymorphism cocrystalline systems other multicomponent forms remains underexplored. study herein aims investigate potential several techniques, liquid-assisted grinding (LAG), solvent evaporation (SE), supercritical enhanced atomization (SEA) electrospraying, cocrystal...
A computationally re-designed molecular loop optimizes helical packing of α-synuclein monomers to seal the aggregation-resistant low-weight tetramer, a key target for Parkinson's disease. Helical are pushed into active conformations during supramolecular assembly, and familial missense mutations double energy barrier tetramerization, preserving pool potentially amyloidogenic monomers.
The experimental finding that α-synuclein (αS) occurs physiologically as a helically folded tetramer begs the question: why are helical tetramers most populated multimers? While is known to resist aggregation, assembly mechanism of αS peptides remains largely unknown. By rationally designing series multimers from dimer octamer, we characterized free energy landscape wild-type and mutated using molecular dynamics computer simulations. Competition between supramolecular packing solvation...
Neurodegeneration involves abnormal aggregation of intrinsically disordered amyloidogenic peptides (IDPs), usually mediated by hydrophobic protein-protein interactions. There is mounting evidence that formation α-helical intermediates an early event during self-assembly amyloid-β42 (Aβ42) and α-synuclein (αS) IDPs in Alzheimer's Parkinson's disease pathogenesis, respectively. However, the driving force behind on-pathway molecular assembly partially folded helical monomers into oligomers...
Neurodegenerative amyloidogenesis begins with the aggregation of intrinsically disordered proteins (IDPs), which is first step in a cascade assembly events that can lead to insoluble fibrous deposits brain tissue. IDP conformations promote formation toxic oligomers remain poorly understood, and are most fundamental target putative treatments for neurodegenerative disease. Rapid advances theory, simulation experimental methods, hold promise reversing protein by identifying developing...
An electrified aqueous-organic interface modulates the conformational plasticity of protein cytochrome c.
Appropriately targeted manipulation of endogenous neural stem progenitor (NSP) cells may contribute to therapies for trauma, stroke, and neurodegenerative disease. A prerequisite such is a better understanding the mechanisms regulating adult NSP in vivo . Indirect data suggest that ciliary neurotrophic factor (CNTF) receptor signaling inhibit neuronal differentiation cells. We challenged subventricular zone (SVZ) with low concentrations CNTF anatomically characterize containing functional...
Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify treat patients according disease stage. LPA known target actin-binding protein gelsolin that key regulator of actin filament assembly. Previous studies have shown the phosphate headgroup alone inadequate bind short chain amino acids in as PIP2-binding domain. Thus, molecular-level detail mechanism binding poorly understood. Here, we model domain gelsolin-actin complex...
Peptides are sustainable alternatives to conventional therapeutics for G protein-coupled receptor (GPCR) linked disorders, promising biocompatible and tailorable next-generation metabolic disorders including type-2 diabetes, as agonists of the glucagon (GCGR) glucagon-like peptide-1 (GLP-1R). However, single agonist peptides activating GLP-1R stimulate insulin secretion also suppress obesity-linked release. Hence, bioactive cotargeting GCGR may remediate blood glucose fatty acid metabolism...
Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify treat patients according disease stage. LPA known target the actin-binding protein gelsolin which key regulator of actin filament assembly. Previous studies have shown that phosphate headgroup alone inadequate bind short chain amino acids in as PIP2-binding domain. Thus, molecular-level detail mechanism binding poorly understood. Here, we model domain gelsolin-actin...
Drug-mediated correction of abnormal biological zinc homeostasis could provide new routes to treating neurodegeneration, cancer, and viral infections. Designing therapeutics facilitate transport intracellularly is hampered by inadequate concentrations endogenous zinc, which often protein-bound in vivo. We found strong evidence that hydroxychloroquine, a drug used treat malaria employed as potential treatment for COVID-19, does not bind across membranes through ionophoric mechanisms, contrary...