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Yusuf Hamied Department of Chemistry

 

Professor Michele Vendruscolo

Professor of Biophysics

Our research

In the last 15 years our research has been focused on the development of methods of characterising the structure, dynamics and interactions of proteins in previously inaccessible states. These methods are based on the use of experimental data, in particular from nuclear magnetic resonance spectroscopy, as structural restraints in molecular dynamics simulations. Through this approach it is possible to obtain information about a variety of protein conformations, as for example those populated during the folding process, and about protein interactions in complex environments, including those generating aggregate species that are associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.

Application to neurodegenerative diseases

More recently, these studies have led us to investigate the physico-chemical principles of proteins homeostasis and their application to the development of therapeutic strategies against neurodegenerative diseases. Starting from the observation that proteins are expressed in the cell at levels close to their solubility limits, we are developing approaches to prevent or delay misfolding disorders based on the enhancement of our quality control mechanisms against protein aggregation.

Watch Professor Vendruscolo discuss his research

Take a tour of the Una Finlay Laboratory in the Centre for Misfolding Diseases

Publications

α-Synuclein driven cell susceptibility in Parkinson’s disease
S Lee, J Breiter, J Beckwith, E Brock, J Lachica, C Toomey, B Fu, M Ryten, L Weiss, N Wood, S Gandhi, M Vendruscolo
(2025)
(doi: 10.21203/rs.3.rs-7375981/v1)
Identification of potent high-affinity secondary nucleation inhibitors of Aβ42 aggregation from an ultra-large chemical library using Deep Docking
M Brezinova, F Brotzakis, R Horne, V Roy Chowdhury, R Gregory, A Gonzalez Diaz, F Gentile, M Vendruscolo
– Molecular Systems Biology
(2025)
(doi: 10.1038/S44320-025-00159-5)
Identification of potent high-affinity secondary nucleation inhibitors of Aβ42 aggregation from an ultra-large chemical library using Deep Docking
M Brezinova, F Brotzakis, R Horne, V Roy Chowdhury, R Gregory, Y Bian, A Gonzalez Diaz, F Gentile, M Vendruscolo
– Molecular Systems Biology
(2025)
(doi: 10.1038/S44320-025-00159-5)
Serial amplification of tau filaments using Alzheimer's brain homogenates and C322A or C322S recombinant tau
A Santambrogio, S Lövestam, MA Metrick, T Löhr, P Xu, NCT Gallagher, B Ghetti, B Caughey, SHW Scheres, M Vendruscolo
– FEBS Letters
(2025)
599,
2768
(doi: 10.1002/1873-3468.70141)
Large-scale visualisation of α-synuclein oligomers in Parkinson’s disease brain tissue
R Andrews, B Fu, CE Toomey, JC Breiter, J Lachica, JS Beckwith, R Tian, EE Brock, L-M Needham, GJ Chant, C Loiseau, A Deconfin, K Baspin, R Popovic, J Evans, Y Goh, B Kurt, L Senicar, M Edmonds, T Bartels, N Bengoa-Vergniory, PJ Magill, Z Jaunmuktane, OJ Freeman, BJM Taylor, J Hardy, T Lashley, M Ryten, M Vendruscolo, NW Wood, LE Weiss, S Gandhi, SF Lee
– Nat Biomed Eng
(2025)
1
(doi: 10.1038/s41551-025-01496-4)
Nanoscale profiling of evolving intermolecular interactions in ageing FUS condensates.
A Miller, Z Toprakcioglu, S Qamar, P St George-Hyslop, FS Ruggeri, TPJ Knowles, M Vendruscolo
– Communications Chemistry
(2025)
8,
284
(doi: 10.1038/S42004-025-01659-Z)
Secondary nucleation of α-Synuclein drives Mitochondria dysfunctions and Lewy body formation in Parkinson’s Disease
EE Prescott, J Wei, EF Garland, A Urbanek, F Capriglia, WH Molenkamp, DP Rhodes, L Heywood, A Schwartzentruber, E Stephen, R Hughes, O Bandmann, MO Collins, S Linse, A Abelein, J Johansson, M Vendruscolo, JR Highly, TPJ Knowles, H Mortiboys, S De
(2025)
(doi: 10.1101/2025.09.17.676873)
Design of Tau Aggregation Inhibitors Using Iterative Machine Learning and a Polymorph-Specific Brain-Seeded Fibril Amplification Assay
A Santambrogio, RI Horne, MA Metrick, NCT Gallagher, ZF Brotzakis, D Rinauro, E Vourkou, K Papanikolopoulou, EMC Skoulakis, S Linse, B Caughey, M Vendruscolo
– Journal of the American Chemical Society
(2025)
147,
35942
(doi: 10.1021/jacs.5c12812)
Microglial activation and alpha-synuclein oligomers drive the early inflammatory phase of Parkinson’s disease
JR Evans, M Grant-Peters, JS Beckwith, CE Toomey, R Popovic, JC Breiter, JW Brenton, A Fairbrother-Browne, S Strohbuecker, J Lachica, M Rodriguez-Lopez, EE Brock, B Fu, L Nahidiazar, P Lopez-Garcia, R Ferguson, RS Saleeb, H Lucas-Clarke, A Penverne, K D’Sa, CW Pang, MH Horrocks, M Vendruscolo, N Wood, SF Lee, M Ryten, S Gandhi
(2025)
(doi: 10.1101/2025.08.25.671921)
Rapid elongation drives the exceptionally fast aggregation of medin, the most common localized human amyloid
M Vendruscolo, VR Chowdhury, R Horne, M Cali, Z Toprakcioglu, S Linse
(2025)
(doi: 10.21203/rs.3.rs-6476074/v1)
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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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