Publications

2023

Synaptic Oligomeric Tau in Alzheimer’s Disease – a Potential Culprit in the Spread of Tau Pathology through the Brain

Colom-Cadena, M., Davies, C., Sirisi, S., Lee, J.-E., Simzer, E., Tzioras, M., Querol-Vilaseca, M., Sánchez-Aced, É., Chang, Y. Y., Holt, K., McGeachan, R., Rose, J., Tulloch, J., Wilkins, L., Smith, C., Andrian, T., Belbin, O., Pujals, S., Horrocks, M. H., Lleó, A., Spires-Jones, T.

Neuron, 111, 1–14, 2023. http://dx.doi.org/10.1016/j.neuron.2023.04.020

Determining the Location of the alpha-Synuclein Dimer Interface Using Native Top-Down Fragmentation and Isotope Depletion-Mass Spectrometry

Jeacock, K., Chappard, A., Gallagher, K. J., Mackay, C. L., Kilgour, D. P. A., Horrocks, M. H., Kunath, T., Clarke, D. J.

Journal of the American Society for Mass Spectrometry, Just published, 2023. http://dx.doi.org/10.1021/jasms.2c00339

Single-Molecule Two-Color Coincidence Detection of Unlabeled alpha-Synuclein Aggregates

Chappard, A., Leighton, C., Saleeb, R.S., Jeacock, K., Ball, S.R., Morris, K., Kantelberg, O., Lee, J., Zacco, E., Pastore, A., Sunde, M., Clarke, D.J., Downey, P., Kunath, T., Horrocks, M.H.

Angewandte Chemie International Edition, e202216771, 2023. http://dx.doi.org/10.1002/anie.202216771

2022

Live-cell super-resolution imaging of actin using LifeAct-14 with a PAINT-based approach

Bhaskar, H., Kleinjan, D.J., Oi, C., Gidden, Z., Rosser, S., Horrocks, M.H.*, Regan, L.*, *Joint corresponding authors

Protein Science, e4558, 2022. http://dx.doi.org/10.1002/pro.4558

Small Fluorogenic Amino Acids for Peptide-Guided Background-Free Imaging

de Moliner, F., Konieczna, Z., Mendive-Tapia, L., Saleeb, R.S., Morris, K., Gonzalez-Vera, J.A., Kaizuka, T., Grant, S.G.N., Horrocks, M.H.*, Vendrell, M.*, *Joint corresponding authors

Angewandte Chemie International Edition, e202216231, 2022. http://dx.doi.org/10.1002/anie.202216231

Protein Aggregation and Calcium Dysregulation Are the Earliest Hallmarks of Synucleinopathy in Human Midbrain Dopaminergic Neurons.

Virdi, G. S., Choi, M. L., Evans, J. R., Yao, Z., Athauda, D., Strohbuecker, S., Wernick, A. I., Alrashidi, H., Melandri, D., Perez-Lloret, J., Angelova, P. R., Sylantyev, S., Eaton, S., Heales, S., Kunath, T., Horrocks, M. H., Abramov, A. Y., Patani, R., Gandhi, S.

npj Parkinson's Disease, 8, 1, 44562, 2022. http://dx.doi.org/10.1101/2022.10.28.514238

pTDP-43 aggregates accumulate in non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis: a case series linking archival surgical biopsies with clinical phenotypic data.

Pattle, S.B., O'Shaughnessy, J., Kantelberg, O., Rifai, O.M., Pate, J., Nellany, K., Hays, N., Arends, M.J., Horrocks, M.H., Waldron, F.M., Gregory, J.M.

The Journal of Pathology: Clinical Research, 9, 44-55, 2022. http://dx.doi.org/10.1002/cjp2.297

Structural Conversion of alpha-Synuclein at the Mitochondria Induces Neuronal Toxicity

Choi, M. L., Chappard, A., Singh, B. P., Maclachlan, C., Rodrigues, M., Fedotova, E., Berezhnov, A. V., De, S., Peddie, C., Athauda, D., Virdi, G. S., Zhang, W., Evans, J. R., Wernick, A., Zanjani, Z. S., Angelova, P. R., Esteras, N., Vinikurov, A., Morris, K., Jeacock, K., Tosatto, L., Little, D., Gissen, P., Clarke, D. J., Kunath, T., Collinson, L., Klenerman, D., Abramov, A. Y.*, Horrocks, M. H.*, Gandhi, S.*, *Joint corresponding authors

Nature Neuroscience, 25, 9, 1134-1148, 2022. http://dx.doi.org/10.1038/s41593-022-01140-3

Synaptic Expression of TAR-DNA-Binding Protein 43 in the Mouse Spinal Cord Determined Using Super-Resolution Microscopy

Broadhead, M. J., Doucet, K., Kantelberg, O. G., Zhu, F., Grant, S. G. N., Horrocks, M. H., Miles, G. B.

bioRxiv , Pre-print, 2022. http://dx.doi.org/10.1101/2022.08.29.505610

Probing TDP-43 Condensation Using an in Silico Designed Aptamer.

Zacco, E., Kantelberg, O., Milanetti, E., Armaos, A., Panei, F. P., Gregory, J., Jeacock, K., Clarke, D. J., Chandran, S., Ruocco, G., Gustincich, S., Horrocks, M. H.*, Pastore, A.*, Tartaglia, G. G.*, *Joint corresponding authors

Nature Communications, 13, 1, 41275, 2022. http://dx.doi.org/10.1038/s41467-022-30944-x

Self-Assembling Protein Surfaces for In Situ Capture of Cell-Free-Synthesized Proteins.

Thornton, E. L., Paterson, S. M., Gidden, Z., Horrocks, M. H., Laohakunakorn, N., Regan, L.

Frontiers in Bioengineering and Biotechnology, 1193, 2022. http://dx.doi.org/10.3389/fbioe.2022.915035

2021

Lipid-Induced Polymorphic Amyloid Fibrils Formation by alpha-Synuclein.

Singh, B. P., Morris, R. J., Horrocks, M. H., Kunath, T., MacPhee, C. E.

bioRxiv, Pre-print, 2021. http://dx.doi.org/10.1101/2021.07.20.453062

2020

PAINT using proteins: A new brush for super-resolution artists

Oi, C., Mochrie, S.J., Horrocks, M.H., Regan, L.

Protein Science, 29, 11, 2142-2149, 2020. http://dx.doi.org/10.1002/pro.3953

A step-by-step protocol for performing LIVE-PAINT super-resolution imaging of proteins in live cells using reversible peptide-protein interactions

Oi, C., Gidden, Z., Holyoake, L., Kantelberg, O., Mochrie, S., Horrocks, M.H.*, Regan, L.*, *Joint corresponding authors

Nature Protocols, Protocol, 2020. http://dx.doi.org/10.21203/rs.3.pex-1043/v1

LIVE-PAINT allows super-resolution microscopy inside living cells using reversible peptide-protein interactions

Oi, C., Gidden, Z., Holyoake, L., Kantelberg, O., Mochrie, S., Horrocks, M.H.*, Regan, L.*, *Joint corresponding authors

Communications Biology, 3, 1, 45200, 2020. http://dx.doi.org/10.1038/s42003-020-01188-6

Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation

Angelova, P.R., Choi, M-L., Berezhnov, A.V., Horrocks, M.H., Hughes, C.D., De, S., Rodrigues, M., Yapom, R., Little, D., Dolt, K.S., Kunath, T., Devine, M.J., Gissen, P., Shchepinov, M.S., Sylantyev, S., Pavlov, E.V., Klenerman, D., Abramov, A.Y., Gandhi, S.

Cell Death and Differentiation, 27, 10, 2781-2796, 2020. http://dx.doi.org/10.1038/s41418-020-0542-z

2019

ASYN-CONA, a novel bead-based assay for detecting early stage alpha-synuclein aggregation.

Pérez-Pi, I., Evans, D.A., Horrocks, M.H., Pham, N.A., Dolt, K.S., Koszela, J., Kunath, T., Auer, M.

Analytical Chemistry, 91, 9, 5582-5590, 2019. http://dx.doi.org/10.1021/acs.analchem.8b03842

SCOTfluors: Small, Conjugatable, Orthogonal and Tunable Fluorophores for in vivo Imaging of Cell Metabolism

Benson, S., Fernandez, A., Barth, N., de Moliner, F., Horrocks, M.H., Herrington, S., Abad, J.L., Delgado, A., Kelly, L., Chang, Z., Feng, Y., Nishiura, M., Hori, Y., Kikuchi, K., Vendrell, M.

Angewandte Chemie International Edition, 131, 21, 6985-6989, 2019. http://dx.doi.org/10.1002/anie.201900465

2018

Mapping Surface Hydrophobicity of alpha-Synuclein Oligomers at the Nanoscale

Lee, J., Sang J.C., Rodrigues M., Carr, A.R., Horrocks, M.H., De, S., Bongiovanni, M.N., Flagmeier, P.,  Dobson, C.M., Wales D.J., Lee, S.F., Klenerman, D.

Nano Letters, 18, 12, 7494-7501, 2018. http://dx.doi.org/10.1021/acs.nanolett.8b02916

Nanoscopic characterization of individual endogenous protein aggregates in human neuronal cells

Whiten, D.R., Zuo, Y., Calo, L., Choi, M., De, S., Flagmeier, P., Wirthensohn, D.C., Kundel, F., Ranasinghe, R.T., Sanchez, S.E., Athauda, D., Lee, S.F., Dobson, C.M., Gandhi, S., Spillantini, M., Klenerman, D., Horrocks, M.H.

ChemBioChem, 19, 19, 2001, 2018. http://dx.doi.org/10.1002/cbic.201800209

Extrinsic Amyloid-Binding Dyes for the Detection of Individual Protein Aggregates in Solution

Taylor, C.G., Meisl, G., Horrocks, M.H., Zetterberg, H., Knowles, T.P.J., Klenerman, D.

Analytical Chemistry, 90, 17, 10385-10393, 2018. http://dx.doi.org/10.1021/acs.analchem.8b02226

Single-Molecule Characterization of the Interactions between Extracellular Chaperones and Toxic alpha-Synuclein Oligomers

Whiten, D.R., Dezerae, D., Horrocks, M.H., Taylor, C.G., De, S., Flagmeier, P., Tosatto, L., Kumita, J.R., Ecroyd, H., Dobson, C.M., Klenerman, D.

Cell Reports, 23, 12, 3492-3500, 2018. http://dx.doi.org/10.1016/j.celrep.2018.05.074

alpha-Synuclein Oligomers Interact with ATP Synthase and Open the Permeability Transition Pore in Parkinson's Disease

Ludtmann, M. H. R.*, Angelova, P. R.*, Horrocks, M. H.*, Choi, M. L., Rodrigues, M., Baev, A. Y., Berezhnov, A. V., Yao, Z., Little, D., Banushi, B., Al-Menhali, A.S., Ranasinghe, R.T., Whiten, D.R., Yapom, R., Dolt, K.S., Devine, M.J., Gissen, P., Kunath, T., Jaganjac, M., Pavlov, E.V., Klenerman, D., Abramov, A.Y., S. Gandhi, S., *Joint first authors

Nature Communications, 9, 1, 42370, 2018. http://dx.doi.org/10.1038/s41467-018-04422-2

A sticky situation: aberrant protein-protein interactions in Parkinson's disease

Brown, J.W.P., Horrocks, M.H.

Seminars in Cell & Developmental Biology, 99, 65-77, 2018. http://dx.doi.org/10.1016/j.semcdb.2018.05.006

Shedding light on aberrant interactions: A review of modern tools for studying protein aggregates

Kundel, F., Tosatto, L.T., Whiten, D.R., Wirthensohn, D.C., Horrocks, M.H.*, Klenerman, D.*, *Joint corresponding authors.

The FEBS Journal, 285, 19, 3604-3630, 2018. http://dx.doi.org/10.1111/febs.14409

Detecting RNA base methylations in single cells by in situ hybridization

Ranasinghe, R.T., Challand, M.R., Ganzinger, K.A., Lewis, B.W., Softley, C., Schmied, W.H., Horrocks, M.H., Shivji, N., Chin, J.W, Spencer, J., Klenerman, D.

Nature Communications, 9, 1, 45200, 2018. http://dx.doi.org/10.1038/s41467-017-02714-7

The small heat shock protein Hsp27 binds alpha-synuclein fibrils, preventing elongation and cytotoxicity

Cox, D., Whiten, D.R., Brown, J.W.P., Horrocks, M.H., San Gil, R., Dobson, C.M., Klenerman, D., van Oijen, A.M., Ecroyd, H.

Journal of Biological Chemistry, 293, 12, 4486-4497, 2018. http://dx.doi.org/10.1074/jbc.M117.813865

Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity

Kundel, F., De, S., Flagmeier, P., Horrocks, M.H., Kjaergaard, M., Shammas, S.L., Jackson, S.E., Dobson, C.M., Klenerman, D.

ACS Chemical Biology, 13, 3, 636-646, 2018. http://dx.doi.org/10.1021/acschembio.7b01039

2017

Nanobodies raised against monomeric alpha-synuclein inhibit fibril formation and destabilize toxic oligomeric species.

Iljina, M., Hong, L, Horrocks, M.H., Ludtmann, M.H., Choi, M.L., Hughes, C.D. Ruggeri, F.S. Guilliams, T., Buell, A.K., Lee, J.E., Gandhi, S., Lee, S.F, Bryant, C.E., Vendruscolo, M., Knowles, T.P.J., Dobson, C.M., De Genst, E., Klenerman, D.

BMC Biology, 15, 1, 41640, 2017. http://dx.doi.org/10.1186/s12915-017-0390-6

PEGylated liposomes associate with Wnt3A protein and expand putative stem cells in human bone marrow populations.

Janeczek, AA, Scarpa, E., Horrocks M.H, Tare, R.S., Rowland, C.A., Jenner, D., Newman, T.A., Oreffo, R.O.C., Lee, S.F., Evans, N.D.

Nanomedicine, 12, 8, 845-863, 2017. http://dx.doi.org/10.2217/nnm-2016-0386

Co-aggregation of κ-Casein and β-Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils.

Raynes, J.K., Crepin, P., Horrocks, M.H., Carver, J.A., Day, L.

Small, 13, 14, 1603591, 2017. http://dx.doi.org/10.1002/smll.201603591

2016

Multi-dimensional super-resolution imaging enables surface hydrophobicity mapping.

Bongiovanni, M.*, Godet, J.*,Horrocks, M.H.*, Tosatto, L., Carr, A.R, Wirthensohn, D.C., Ranasinghe, R.T., Lee, J., Ponjavic, A., Fritz, J.V., Dobson, C.M., Klenerman, D., Lee, S.F., *Joint first authors

Nature Communications, 7, 1, 45170, 2016. http://dx.doi.org/10.1038/ncomms13544

The remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions.

Jonsson P., Southcombe J., Mafalda A., Santos A.M., Fernandes R.A., McColl J., Chang V.C., Godkin A., Dunne P.D., Horrocks M.H., Palayret M., Fugger L., Xu X., Davis S.J., Klenerman D.

Proceedings of the National Academy of Sciences, 113, 20, 5682-5687, 2016. http://dx.doi.org/10.1073/pnas.1513918113

PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits.

Broadhead M.J., Horrocks M.H., Zhu F., Muresan L., Benavides-Piccione R., DeFelipe J., Fricker D., Kopanitsa M.V., Duncan R.R., Klenerman D., Komiyama N.H., Lee S.F., Grant S.G.N.

Scientific Reports, 6, 1, 41640, 2016. http://dx.doi.org/10.1038/srep24626

A kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading.

Iljina,M., Garciaa, G.A., Horrocks, M.H., Tosatto, L., Choi, M.L., Ganzinger, K.A., Abramov, A.Y., Gandhi, S., Wood, N.W., Cremades, N.,Dobson, C.M. , Knowles, T.P.J., Klenerman, D.

Proceedings of the National Academy of Sciences, 113, 9, E1206-E1215, 2016. http://dx.doi.org/10.1073/pnas.1524128113

Single-molecule imaging of individual amyloid protein aggregates in human biofluids.

Horrocks M. H., Lee S.F., Gandhi S., Magdalinou N.K., Chen S.W., Devine M.J., Toasatto, L., Kjaergaard M., Beckwith J.S., Zetterberg H., Iljina M., Cremades N., Dobson C.M., Wood N.W., Klenerman D.

ACS Chemical Neuroscience, 7, 3, 399-406, 2016. http://dx.doi.org/10.1021/acschemneuro.5b00324

Calcium is a key factor in alpha-synuclein induced neurotoxicity.

Angelova, P., Ludtmann, M., Horrocks, M.H., Negoda, A., Cremades, N., Klenerman, D., Dobson, C.M., Wood, N., Pavlov, E., Gandhi, S., Abramov, A.

Journal of Cell Science, 129, 9 , 1792-1801, 2016. http://dx.doi.org/10.1242/jcs.180737

2015

Alpha-synuclein oligomers interact with metal ions to induce oxidative stress and neuronal death in Parkinson's disease.

Deas, E., Cremades, N., Angelova, P.R., Ludtmann, M., Yao, Z., Chen, S., Horrocks, M.H., Banushi, B., Little, D., Devine, M., Gissen P., Klenerman, D., Dobson, C.M., Wood, N., Gandhi, S., Abramov. A.Y.

Antioxidants and redox signaling, 24, 7, 376-391, 2015. http://dx.doi.org/10.1089/ars.2015.6343

Single-molecule FRET studies on alpha-synuclein oligomerization of Parkinson's disease genetically related mutants.

Horrocks, M.H., Tosatto, L., Dear, A.J., Knowles, T.P.J., Dalla Serra, M., Dobson, C.M., Klenerman, D.

Scientific Reports, 5, 1, 45261, 2015. http://dx.doi.org/10.1038/srep16696

Fast flow microfluidics and single-molecule fluorescence for the rapid characterization of alpha-synuclein oligomers.

Horrocks, M.H., Tosatto, L., Dear, A.J., Garcia, G.A., Iljina, M., Cremades, N., Dalla Serra, M., Knowles, T.P.J., Dobson, C.M., Klenerman, D.

Analytical Chemistry, 87, 17, 8818-8826, 2015. http://dx.doi.org/10.1021/acs.analchem.5b01811

Aggregated alpha-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons.

Reeve, A.K., Ludtmann, M.H.R, Angelova, P.R., Simcox, E.M., Horrocks, M.H., Klenerman, D., Gandhi, S., Turnbull, D.M., Abramov, A.Y.

Cell Disease and Death, 6,7, e1820-e1820, 2015. http://dx.doi.org/10.1038/cddis.2015.166

Lipid peroxidation is essential for alpha-synuclein-induced cell death.

Angelova, P.R., Horrocks, M.H., Klenerman D, Gandhi S, Abramov, A.Y., Shchepinov, M.S

Journal of Neurochemistry, 133, 4, 582-589, 2015. http://dx.doi.org/10.1111/jnc.13024

A mechanistic model of tau amyloid aggregation based on direct observation of oligomers.

Shammas, S. L., Garcia, G. A., Kumar S., A., Kjaergaard M., Horrocks, M.H., Shivji N., Mandelkow, E., Knowles T.P.J., Mandelkow E., Klenerman, D..

Nature Communications, 6,1, 45200, 2015. http://dx.doi.org/10.1038/ncomms8025

2014

Bayesian Inference of Accurate Population Sizes and FRET Efficiencies from Single Diffusing Biomolecules.

Murphy, R.M., Danezis, D., Horrocks, M.H., Jackson, S.E., Klenerman, D.

Analytical Chemistry, 86, 17, 8603-8612, 2014. http://dx.doi.org/10.1021/ac501188r

The changing point-spread function: single-molecule-based super-resolution imaging.

Horrocks, M.H., Palayret, M., Klenerman, D., Lee, S.F.

Histochemistry and Cell Biology, 141, 6, 577-585, 2014. http://dx.doi.org/10.1007/s00418-014-1186-1

2013

Single-molecule measurements of transient biomolecular complexes through microfluidic dilution

Horrocks, M.H., Rajah, L., Jonsson, P., Kjaergaard, M., Vendruscolo, M., Knowles, T.P.J., Klenerman, D.

Analytical Chemistry, 85, 14, 6855-6859, 2013. http://dx.doi.org/10.1021/ac4010875

2012

Ubiquitin chain conformation regulates recognition and activity of interacting proteins.

Ye, Y., Blaser, G., Horrocks, M.H., Ruedas-Rama, M.J., Ibrahim, S., Zhukov, A.A., Orte, A., Klenerman, D., Jackson, S.E., Komander, D.

Nature, 492, 7428, 266-270, 2012. http://dx.doi.org/10.1038/nature11722

Single molecule fluorescence under conditions of fast flow.

Horrocks, M.H., Li, H., Shim, J.-U., Ranasinghe, R.T., Clarke, R.W., Huck, W.T.S., Abell, C., Klenerman, D.

Analytical Chemistry, 84, 1, 179-185, 2012. http://dx.doi.org/10.1021/ac202313d

Patents

1. (WO2016001644) Diagnosis and Treatment of Neurodegenerative Disorders