Department

Institute

Research Theme Adaptive Brain Computations Neurons, Circuits and Networks

Research Focus

Keywords

Alzheimer's Disease

Parkinson's Disease

Drug Discovery

Protein Misfolding & Aggregation

Clinical Conditions

Alzheimer's disease

Parkinson's disease

Equipment & Techniques

Computational modelling

Cell culture

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Professor Michele Vendruscolo

University Position

Professor

Interests

Our research at the Centre for Misfolding Diseases (https://www.cmd.ch.cam.ac.uk/) is aimed at understanding the molecular origins of neurodegenerative disorders. We have set up an interdisciplinary programme that brings together methods and concepts from chemistry, physics, engineering, genetics and medicine. We are using a combination of in vitro, in silico and in vivo approaches to study protein homeostasis through the analysis of the effects that result from its alteration in specific proteins, from either amino acid mutations, or changes in concentration and solubility, or the interactions with other molecules. This programme is generating new insights into the mechanism through which physical and chemical sciences can increase our understanding of the nature and consequences of the failure to maintain protein homeostasis and its association with ageing and neurodegenerative disorders.

Associated News Items

Key Publications

Probing the effects of N-terminal acetylation on α-synuclein structure, aggregation and cytotoxicity.

DOI: http://doi.org/10.1016/bs.mie.2022.09.003
Journal:
E-pub date: 1 Aug 2023
Authors: R Bell, M Vendruscolo, JR Kumita

Effects of N-terminal Acetylation on the Aggregation of Disease-related α-synuclein Variants.

DOI: http://doi.org/10.1016/j.jmb.2022.167825
Journal: J Mol Biol
E-pub date: 15 Jan 2023
Authors: R Bell, M Castellana-Cruz, A Nene, RJ Thrush, CK Xu, JR Kumita, M Vendruscolo

Phase Separation of FUS is Modulated by Methylation State of Cation-π Interactions and Interaction with TNPO1

DOI: http://doi.org/10.1016/j.cell.2018.03.056
Journal: Cell
E-pub date: 19 Apr 2018
Authors: PH St George-Hyslop, S Qamar, G Wang, SJ Randle, FS Ruggeri, J Varela, CF Kaminski, GS Kaminski, M Vendruscolo, TPJ Knowles, D Klenerman, CE Holt, Q Lin, W meadows

ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function.

DOI: http://doi.org/10.1016/j.neuron.2015.10.030
Journal: Neuron
E-pub date: 18 Nov 2015
Authors: T Murakami, S Qamar, JQ Lin, GSK Schierle, E Rees, A Miyashita, AR Costa, RB Dodd, FTS Chan, CH Michel, D Kronenberg-Versteeg, Y Li, S-P Yang, Y Wakutani, W Meadows, RR Ferry, L Dong, GG Tartaglia, G Favrin, W-L Lin, DW Dickson, M Zhen, D Ron, G Schmitt-Ulms, PE Fraser, NA Shneider, C Holt, M Vendruscolo, CF Kaminski, P St George-Hyslop

Publications

An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson’s disease patients.

DOI: http://doi.org/10.1039/d2sc00066k
Journal: Chem Sci
E-pub date: 30 Nov 2022
Authors: K Kulenkampff, D Emin, R Staats, YP Zhang, L Sakhnini, A Kouli, O Rimon, E Lobanova, CH Williams-Gray, FA Aprile, P Sormanni, D Klenerman, M Vendruscolo

Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease

DOI: http://doi.org/10.1038/s41467-022-33252-6
Journal: Nat Commun
E-pub date: 20 Sep 2022
Authors: D Emin, YP Zhang, E Lobanova, A Miller, X Li, Z Xia, H Dakin, DI Sideris, JYL Lam, RT Ranasinghe, A Kouli, Y Zhao, S De, TPJ Knowles, M Vendruscolo, FS Ruggeri, FI Aigbirhio, CH Williams-Gray, D Klenerman

Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers.

DOI: http://doi.org/10.3389/fnins.2021.680026
Journal: Front Neurosci
E-pub date: 1 Aug 2021
Authors: R Limbocker, R Staats, S Chia, FS Ruggeri, B Mannini, CK Xu, M Perni, R Cascella, A Bigi, LR Sasser, NR Block, AK Wright, RP Kreiser, ET Custy, G Meisl, S Errico, J Habchi, P Flagmeier, T Kartanas, JE Hollows, LT Nguyen, K LeForte, D Barbut, JR Kumita, C Cecchi, M Zasloff, TPJ Knowles, CM Dobson, F Chiti, M Vendruscolo

A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers.

DOI: http://doi.org/10.1038/s42003-020-01490-3
Journal: Commun Biol
E-pub date: 4 Jan 2021
Authors: R Cataldi, S Chia, K Pisani, FS Ruggeri, CK Xu, T Šneideris, M Perni, S Sarwat, P Joshi, JR Kumita, S Linse, J Habchi, TPJ Knowles, B Mannini, CM Dobson, M Vendruscolo

Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro.

DOI: http://doi.org/10.18632/aging.202138
Journal: Aging (Albany NY)
E-pub date: 4 Nov 2020
Authors: D Frankel, M Davies, B Bhushan, Y Kulaberoglu, P Urriola-Munoz, J Bertrand-Michel, MR Pergande, AA Smith, S Preet, TJ Park, M Vendruscolo, KS Rankin, SM Cologna, JR Kumita, N Cenac, E St John Smith

Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism.

DOI: http://doi.org/10.1038/s42003-020-01140-8
Journal: Commun Biol
E-pub date: 13 Aug 2020
Authors: R Limbocker, B Mannini, FS Ruggeri, R Cascella, CK Xu, M Perni, S Chia, SW Chen, J Habchi, A Bigi, RP Kreiser, AK Wright, JA Albright, T Kartanas, JR Kumita, N Cremades, M Zasloff, C Cecchi, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson

Rationally Designed Antibodies as Research Tools to Study the Structure-Toxicity Relationship of Amyloid-β Oligomers.

DOI: http://doi.org/10.3390/ijms21124542
Journal: Int J Mol Sci
E-pub date: 25 Jun 2020
Authors: R Limbocker, B Mannini, R Cataldi, S Chhangur, AK Wright, RP Kreiser, JA Albright, S Chia, J Habchi, P Sormanni, JR Kumita, FS Ruggeri, CM Dobson, F Chiti, FA Aprile, M Vendruscolo

Chemical and mechanistic analysis of photodynamic inhibition of Alzheimer’s β-amyloid aggregation.

DOI: http://doi.org/10.1039/c8cc09288e
Journal: Chem Commun (Camb)
E-pub date: 25 Jan 2019
Authors: M Ahn, BI Lee, S Chia, J Habchi, JR Kumita, M Vendruscolo, CM Dobson, CB Park

Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes.

DOI: http://doi.org/10.1038/s41467-018-07699-5
Journal: Nat Commun
E-pub date: 15 Jan 2019
Authors: R Limbocker, S Chia, FS Ruggeri, M Perni, R Cascella, GT Heller, G Meisl, B Mannini, J Habchi, TCT Michaels, PK Challa, M Ahn, ST Casford, N Fernando, CK Xu, ND Kloss, SIA Cohen, JR Kumita, C Cecchi, M Zasloff, S Linse, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

DOI: http://doi.org/10.1021/acschembio.8b00466
Journal: ACS Chem Biol
E-pub date: 17 Aug 2018
Authors: M Perni, P Flagmeier, R Limbocker, R Cascella, FA Aprile, C Galvagnion, GT Heller, G Meisl, SW Chen, JR Kumita, PK Challa, JB Kirkegaard, SIA Cohen, B Mannini, D Barbut, EAA Nollen, C Cecchi, N Cremades, TPJ Knowles, F Chiti, M Zasloff, M Vendruscolo, CM Dobson

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes.

DOI: http://doi.org/10.1038/s41557-018-0031-x
Journal: Nat Chem
E-pub date: 1 Jun 2018
Authors: J Habchi, S Chia, C Galvagnion, TCT Michaels, MMJ Bellaiche, FS Ruggeri, M Sanguanini, I Idini, JR Kumita, E Sparr, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo

Amyloid-like Fibrils from an α-Helical Transmembrane Protein.

DOI: http://doi.org/10.1021/acs.biochem.7b00157
Journal: Biochemistry
E-pub date: 27 Jun 2017
Authors: K Stroobants, JR Kumita, NJ Harris, DY Chirgadze, CM Dobson, PJ Booth, M Vendruscolo

Inhibition of α-Synuclein Fibril Elongation by Hsp70 Is Governed by a Kinetic Binding Competition between α-Synuclein Species.

DOI: http://doi.org/10.1021/acs.biochem.6b01178
Journal: Biochemistry
E-pub date: 7 Mar 2017
Authors: FA Aprile, P Arosio, G Fusco, SW Chen, JR Kumita, A Dhulesia, P Tortora, TPJ Knowles, M Vendruscolo, CM Dobson, N Cremades

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer’s disease.

DOI: http://doi.org/10.1073/pnas.1615613114
Journal: Proc Natl Acad Sci U S A
E-pub date: 10 Jan 2017
Authors: J Habchi, S Chia, R Limbocker, B Mannini, M Ahn, M Perni, O Hansson, P Arosio, JR Kumita, PK Challa, SIA Cohen, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo

Structure and dynamics of the integrin LFA-1 I-domain in the inactive state underlie its inside-out/outside-in signaling and allosteric mechanisms.

DOI: http://doi.org/10.1016/j.str.2014.12.020
Journal: Structure
E-pub date: 7 Apr 2015
Authors: P Kukic, HT Alvin Leung, F Bemporad, FA Aprile, JR Kumita, A De Simone, C Camilloni, M Vendruscolo

Molecular determinants of the aggregation behavior of alpha- and beta-synuclein.

DOI: http://doi.org/10.1110/ps.073181508
Journal: Protein Sci
E-pub date: 1 May 2008
Authors: RC Rivers, JR Kumita, GG Tartaglia, MM Dedmon, A Pawar, M Vendruscolo, CM Dobson, J Christodoulou