1. Lipid peroxidation is essential for α-synuclein-induced cell death.

    Journal of Neurochemistry 133(4):582 (2015) PMID 25580849 PMCID PMC4471127

    Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated α-synuclein (α-Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric α-Syn on ...
  2. On-demand delivery of single DNA molecules using nanopipets.

    ACS Nano 9(4):3587 (2015) PMID 25794527

    Understanding the behavioral properties of single molecules or larger scale populations interacting with single molecules is currently a hotly pursued topic in nanotechnology. This arises from the potential such techniques have in relation to applications such as targeted drug delivery, early st...
  3. Structural characterization of toxic oligomers that are kinetically trapped during α-synuclein fibril formation.

    PNAS 112(16):E1994 (2015) PMID 25855634 PMCID PMC4413268

    We describe the isolation and detailed structural characterization of stable toxic oligomers of α-synuclein that have accumulated during the process of amyloid formation. Our approach has allowed us to identify distinct subgroups of oligomers and to probe their molecular architectures by using c...
  4. SICM-Based Nanodelivery System for Local TRPV1 Stimulation

    Biophysical Journal 108(2):332a (2015)

  5. Single-molecule FRET reveals hidden complexity in a protein energy landscape.

    Structure 23(1):190 (2015) PMID 25565106 PMCID PMC4291146

    Here, using single-molecule FRET, we reveal previously hidden conformations of the ankyrin-repeat domain of AnkyrinR, a giant adaptor molecule that anchors integral membrane proteins to the spectrin-actin cytoskeleton through simultaneous binding of multiple partner proteins. We show that the an...
  6. Single-Molecule FRET Reveals Hidden Complexity in a Protein Energy Landscape.

    Structure 23(1):190 (2015) PMID 25565106

    Here, using single-molecule FRET, we reveal previously hidden conformations of the ankyrin-repeat domain of AnkyrinR, a giant adaptor molecule that anchors integral membrane proteins to the spectrin-actin cytoskeleton through simultaneous binding of multiple partner proteins. We show that the an...
  7. Single-Molecule FRET Reveals Hidden Complexity in a Protein Energy Landscape.

    Structure 23(1):190 (2015) PMID 25565106 PMCID PMC4291146

    Here, using single-molecule FRET, we reveal previously hidden conformations of the ankyrin-repeat domain of AnkyrinR, a giant adaptor molecule that anchors integral membrane proteins to the spectrin-actin cytoskeleton through simultaneous binding of multiple partner proteins. We show that the an...
  8. A mechanistic model of tau amyloid aggregation based on direct observation of oligomers.

    Nature Communications 6:7025 (2015) PMID 25926130 PMCID PMC4421837

    Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods ...
  9. Virtual-'light-sheet' single-molecule localisation microscopy enables quantitative optical sectioning for super-resolution imaging.

    PLoS ONE 10(4):e0125438 (2015) PMID 25884495 PMCID PMC4401716

    Single-molecule super-resolution microscopy allows imaging of fluorescently-tagged proteins in live cells with a precision well below that of the diffraction limit. Here, we demonstrate 3D sectioning with single-molecule super-resolution microscopy by making use of the fitting information that i...
  10. Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus.

    Scientific reports 5:10934 (2015) PMID 26055072 PMCID PMC4460729

    The acute neurotoxicity of oligomeric forms of amyloid-β 1-42 (Aβ) is implicated in the pathogenesis of Alzheimer's disease (AD). However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects c...
  11. Single-molecule imaging reveals that small amyloid-β1-42 oligomers interact with the cellular prion protein (PrP(C)).

    ChemBioChem 15(17):2515 (2014) PMID 25294384

    Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer's disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by...
  12. Single-Molecule Imaging Reveals that Small Amyloid-β1-42 Oligomers Interact with the Cellular Prion Protein (PrP(C) ).

    ChemBioChem 15(17):2515 (2014) PMID 25294384

    Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer's disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by...
  13. Single-molecule imaging reveals that small amyloid-β1-42 oligomers interact with the cellular prion protein (PrP(C)).

    ChemBioChem 15(17):2515 (2014) PMID 25294384

    Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer's disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by...
  14. Single-molecule imaging reveals that small amyloid-β1-42 oligomers interact with the cellular prion protein (PrP(C)).

    ChemBioChem 15(17):2515 (2014) PMID 25294384 PMCID PMC4371635

    Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer's disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by...
  15. Single-Molecule Imaging Reveals that Small Amyloid-β1-42 Oligomers Interact with the Cellular Prion Protein (PrP(C) ).

    ChemBioChem 15(17):2515 (2014) PMID 25294384

    Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer's disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by...
  16. Quantification of DNA-associated proteins inside eukaryotic cells using single-molecule localization microscopy.

    Nucleic Acids Research 42(19):e146 (2014) PMID 25106872 PMCID PMC4231725

    Development of single-molecule localization microscopy techniques has allowed nanometre scale localization accuracy inside cells, permitting the resolution of ultra-fine cell structure and the elucidation of crucial molecular mechanisms. Application of these methodologies to understanding proces...
  17. Quantification of DNA-associated proteins inside eukaryotic cells using single-molecule localization microscopy.

    Nucleic Acids Research 42(19):e146 (2014) PMID 25106872 PMCID PMC4231725

    Development of single-molecule localization microscopy techniques has allowed nanometre scale localization accuracy inside cells, permitting the resolution of ultra-fine cell structure and the elucidation of crucial molecular mechanisms. Application of these methodologies to understanding proces...
  18. Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules.

    Analytical chemistry 86(17):8603 (2014) PMID 25105347

    It is of significant biophysical interest to obtain accurate intramolecular distance information and population sizes from single-molecule Förster resonance energy transfer (smFRET) data obtained from biomolecules in solution. Experimental methods of increasing cost and complexity are being deve...
  19. Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules.

    Analytical chemistry 86(17):8603 (2014) PMID 25105347

    It is of significant biophysical interest to obtain accurate intramolecular distance information and population sizes from single-molecule Förster resonance energy transfer (smFRET) data obtained from biomolecules in solution. Experimental methods of increasing cost and complexity are being deve...
  20. The changing point-spread function: single-molecule-based super-resolution imaging.

    Histochemistry 141(6):577 (2014) PMID 24509806

    Over the past decade, many techniques for imaging systems at a resolution greater than the diffraction limit have been developed. These methods have allowed systems previously inaccessible to fluorescence microscopy to be studied and biological problems to be solved in the condensed phase. This ...