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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

Global kinetic model of lipid-induced α-synuclein aggregation and its inhibition by small molecules.

A Stevenson, R Staats, AJ Dear, D Voderholzer, JE Dreier, G Meisl, R Guido, TPJ Knowles, C Galvagnion, AK Buell, M Vendruscolo, TCT Michaels

– Proceedings of the National Academy of Sciences of the United States of America

(2025)

122,

e2422427122

(doi: 10.1073/pnas.2422427122)

Proteostasis signatures in human diseases

CM Lim, M Vendruscolo

– Plos Computational Biology

(2025)

21,

e1013155

(doi: 10.1371/journal.pcbi.1013155)

Destabilization of Helix III Initiates Early Serum Amyloid A Misfolding by Exposing Its Amyloidogenic Core

H Nadwa, ZF Brotzakis, A Santucci, D Braconi, M Vendruscolo

(2025)

(doi: 10.1101/2025.05.27.656333)

The thermodynamic hypothesis of protein aggregation

M Vendruscolo

– Molecular aspects of medicine

(2025)

103,

101364

(doi: 10.1016/j.mam.2025.101364)

Prediction of Antibody Non-Specificity using Protein Language Models and Biophysical Parameters

LI Sakhnini, L Beltrame, S Fulle, P Sormanni, A Henriksen, N Lorenzen, M Vendruscolo, D Granata

(2025)

(doi: 10.1101/2025.04.28.650927)

Rational Design of Single-Domain Antibodies Targeting the Central Nervous System Neurite Outgrowth Inhibitor Nogo-A

V Roy Chowdhury, A Röntgen, M Greenig, Y Méndez Gómez, SP Spiegel, M Nowinska, A Ramon, P Sormanni, A Chan, M Vendruscolo

– Wiley Interdisciplinary Reviews: RNA

(2025)

4,

e70012

(doi: 10.1002/appl.70012)

Aggregation of α-synuclein splice isoforms through a phase separation pathway.

A Röntgen, Z Toprakcioglu, ST Dada, OM Morris, TPJ Knowles, M Vendruscolo

– Science Advances

(2025)

11,

eadq5396

(doi: 10.1126/sciadv.adq5396)

Aggregation of α-Synuclein Splice Isoforms through a Phase Separation Pathway

A Roentgen, Z Toprakcioglu, ST Dada, OM Morris, TPJ Knowles, M Vendruscolo

– Science Advances

(2025)

(doi: 10.1126/sciadv.adq5396)

Linking Aβ and tau in the amyloid cascade through the intersection of their proteostasis networks

CM Lim, J Hardy, M Vendruscolo

(2025)

(doi: 10.1101/2025.03.28.646065)

Serial amplification of tau filaments using Alzheimer’s brain homogenates and C322A or C322S recombinant tau

A Santambrogio, S Lövestam, MA Metrick, TS Lohr, P Xu, B Caughey, SHW Scheres, M Vendruscolo

(2025)

(doi: 10.1101/2025.03.29.646137)