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Your search keyword '"Horrocks, Mathew H."' showing total 13 results
Start Over Author "Horrocks, Mathew H." Publisher american chemical society (acs)
13 results on '"Horrocks, Mathew H."'

1. Imaging Proteins Sensitive to Direct Fusions Using Transient Peptide–Peptide Interactions

Author

Gidden, Zoe, primary, Oi, Curran, additional, Johnston, Emily J., additional, Konieczna, Zuzanna, additional, Bhaskar, Haresh, additional, Mendive-Tapia, Lorena, additional, de Moliner, Fabio, additional, Rosser, Susan J., additional, Mochrie, Simon G. J., additional, Vendrell, Marc, additional, Horrocks, Mathew H., additional, and Regan, Lynne, additional

Published
2023
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4. Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale

Author

Lee, Ji-Eun, primary, Sang, Jason C., additional, Rodrigues, Margarida, additional, Carr, Alexander R., additional, Horrocks, Mathew H., additional, De, Suman, additional, Bongiovanni, Marie N., additional, Flagmeier, Patrick, additional, Dobson, Christopher M., additional, Wales, David J., additional, Lee, Steven F., additional, and Klenerman, David, additional

Published
2018
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7. Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules

Author

Murphy, Rebecca R, Danezis, George, Horrocks, Mathew H, Jackson, Sophie E, Klenerman, David, Jackson, Sophie [0000-0002-7470-9800], Klenerman, David [0000-0001-7116-6954], and Apollo - University of Cambridge Repository

Subjects
Diffusion, Quantitative Biology::Biomolecules, Fluorescence Resonance Energy Transfer, Bayes Theorem, DNA, Monte Carlo Method, Algorithms, Markov Chains
Abstract

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 developed to improve the accuracy and precision of data collection. However, the analysis of smFRET data sets currently relies on simplistic, and often arbitrary methods, for the selection and denoising of fluorescent bursts. Although these methods are satisfactory for the analysis of simple, low-noise systems with intermediate FRET efficiencies, they display systematic inaccuracies when applied to more complex systems. We have developed an inference method for the analysis of smFRET data from solution studies based on rigorous model-based Bayesian techniques. We implement a Monte Carlo Markov chain (MCMC) based algorithm that simultaneously estimates population sizes and intramolecular distance information directly from a raw smFRET data set, with no intermediate event selection and denoising steps. Here, we present both our parametric model of the smFRET process and the algorithm developed for data analysis. We test the algorithm using a combination of simulated data sets and data from dual-labeled DNA molecules. We demonstrate that our model-based method systematically outperforms threshold-based techniques in accurately inferring both population sizes and intramolecular distances.

Published
2014

8. Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids

Author

Horrocks, Mathew H., primary, Lee, Steven F., additional, Gandhi, Sonia, additional, Magdalinou, Nadia K., additional, Chen, Serene W., additional, Devine, Michael J., additional, Tosatto, Laura, additional, Kjaergaard, Magnus, additional, Beckwith, Joseph S., additional, Zetterberg, Henrik, additional, Iljina, Marija, additional, Cremades, Nunilo, additional, Dobson, Christopher M., additional, Wood, Nicholas W., additional, and Klenerman, David, additional

Published
2016
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13. Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale

Author

Lee, Ji-Eun, Sang, Jason C, Rodrigues, Margarida, Carr, Alexander R, Horrocks, Mathew H, De, Suman, Bongiovanni, Marie N, Flagmeier, Patrick, Dobson, Christopher M, Wales, David J, Lee, Steven F, and Klenerman, David

Subjects
alpha-synuclein, Optical Imaging, Nile red, spectral imaging, Parkinson Disease, Protein Aggregation, Pathological, 3. Good health, protein aggregation, Protein Aggregates, Solubility, Super-resolution spectroscopy, Humans, Protein Multimerization, Hydrophobic and Hydrophilic Interactions, hydrophobicity, Fluorescent Dyes
Abstract

Proteins fold into a single structural ensemble but can also misfold into many diverse structures including small aggregates and fibrils, which differ in their toxicity. The aggregate surface properties play an important role in how they interact with the plasma membrane and cellular organelles, potentially inducing cellular toxicity, however, these properties have not been measured to date due to the lack of suitable methods. Here, we used a spectrally resolved, super-resolution imaging method combined with an environmentally sensitive fluorescent dye to measure the surface hydrophobicity of individual aggregates formed by the protein α-synuclein (αS), whose aggregation is associated with Parkinson's disease. We show that the surface of soluble oligomers is more hydrophobic than fibrils and populates a diverse range of coexisting states. Overall, our data show that the conversion of oligomers to fibril-like aggregates and ultimately to fibrils results in a reduction in both hydrophobicity and the variation in hydrophobicity. This funneling characteristic of the energy landscape explains many of the observed properties of αS aggregates and may be a common feature of aggregating proteins.

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