Publications

2023

53. Two-Color Coincidence Single-Molecule Pull-down for the Specific Detection of Disease-Associated Protein Aggregates

Saleeb, R.S., Leighton, C., Lee, J., O’Shaughnessy, J., Jeacock, K., Chappard, A., Cumberland, R., Zhao, T., Ball, S.R., Sunde, M., Clarke, D.J., Piche, K., McPhail, J.A., Louwrier, A., Angers, R., Gandhi, S., Downey, P., Kunath, T., Horrocks, M.H.

Science Advances, 9, eadi7359, 2023. http://dx.doi.org/10.1126/sciadv.adi7359

52. RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS.

Spence, H., Waldron, F. M., Saleeb, R. S., Brown, A.-L., Rifai, O. M., Gilodi, M., Read, F., Roberts, K., Milne, G., Wilkinson, D., O’Shaughnessy, J., Pastore, A., Fratta, P., Shneider, N., Tartaglia, G. G., Zacco, E., Horrocks, M. H., Gregory, J. M.

bioRxiv, Pre-print, 2023. http://dx.doi.org/10.1101/2023.10.24.563701

51. Imaging Proteins Sensitive to Direct Fusions Using Transient Peptide-Peptide Interactions.

Gidden, Z., Oi, C., Johnston, E.J., Konieczna, Z., Bhaskar, H., Mendive-Tapia, L., de Moliner, F., Rosser, S.J., Mochrie, S. G. J., Vendrell, M., Horrocks, M. H., Regan, L.

ACS Nano Letters, Just published., 2023. http://dx.doi.org/10.1021/acs.nanolett.3c03780

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

Broadhead, M. J., Ayvazian-Hancock, A., Doucet, K., Kantelberg, O. G., Zhu, F., Motherwell, L., Grant, S. G. N., Horrocks, M. H., Miles, G. B.

Frontiers in Molecular Neuroscience, 16, 2023. http://dx.doi.org/10.3389/fnmol.2023.1027898

49. Prediction of mechanistic subtypes of Parkinson’s using patient derived stem cell models

D, Karishma, Evans, J.R., Virdi, G.S., Vecchi, G., Adam, A., Bertolli, O., Fleming, J., Chang, H., Leighton, C., Horrocks, M.H., Athauda, D., Choi, M.L., Gandhi, S.

Nature Machine Intelligence, Just published, 2023. http://dx.doi.org/10.1038/s42256-023-00702-9

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

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

Protein Science, Just published, 2023. http://dx.doi.org/10.1002/pro.4736

47. The Organization and Turnover of Synaptic Proteins within Molecular Supercomplexes

Morris, K., Bulovaite, E., Kaizuka, T., Adams, C., Komiyama, N., Grant, S. G. N., Horrocks, M. H.

bioRxiv, Pre-print, 2023. http://dx.doi.org/10.1101/2023.07.13.548866

46. 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

45. 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, 34, 5, 847–856, 2023. http://dx.doi.org/10.1021/jasms.2c00339

44. 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

43. 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

42. 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

41. 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., Nirujogi, R. S., Wernick, A. I., Pelegrina-Hidalgo, N., Leighton, C., Saleeb, R. S., Kopach, O., Alrashidi, H., Melandri, D., Perez-Lloret, J., Angelova, P. R., Sylantyev, S., Eaton, S., Heales, S., Rusakov, D. A., Alessi, D. R., Kunath, T., Horrocks, M. H., Abramov, A. Y., Patani, R., Gandhi, S.

npj Parkinson's Disease, 8, 1, 44562, 2022. http://dx.doi.org/10.1038/s41531-022-00423-7

40. 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

39. 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

38. 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

37. 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

2020

36. 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

35. 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

34. 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

33. 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

32. 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

31. 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

30. 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

29. 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

28. 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

27. 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

26. 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

25. 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

24. 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

23. 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

22. 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

21. 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

20. 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

19. 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

18. 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

17. 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

16. 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

15. 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

14. 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

13. 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

12. 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

11. 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

10. 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

9. 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

8. 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

7. 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

6. 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

5. 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

4. 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

3. 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

2. 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

1. 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