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Centre for Misfolding Diseases

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

Pharmacological inhibition of α-synuclein aggregation within liquid condensates
ST Dada, Z Toprakcioglu, MP Cali, A Röntgen, MC Hardenberg, OM Morris, LK Mrugalla, TPJ Knowles, M Vendruscolo
– Nat Commun
(2024)
15,
3835
Discovery of potent inhibitors of α-synuclein aggregation using structure-based iterative learning
RI Horne, EA Andrzejewska, P Alam, ZF Brotzakis, A Srivastava, A Aubert, M Nowinska, RC Gregory, R Staats, A Possenti, S Chia, P Sormanni, B Ghetti, B Caughey, TPJ Knowles, M Vendruscolo
– Nature chemical biology
(2024)
20,
634
RASP: Optimal Single Puncta Detection in Complex Cellular Backgrounds
B Fu, E Brock, R Andrews, J Breiter, R Tian, C Toomey, J Lachica, T Lashley, M Ryten, N Wood, M Vendruscolo, S Gandhi, L Weiss, J Beckwith, S Lee
– The Journal of Physical Chemistry B
(2024)
128,
3585
A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions
S Chia, RL Cataldi, FS Ruggeri, R Limbocker, I Condado-Morales, K Pisani, A Possenti, S Linse, TPJ Knowles, J Habchi, B Mannini, M Vendruscolo
– ACS Chemical Neuroscience
(2024)
15,
1125
Targeted protein editing with an antibody-based system
M Vendruscolo, O Rimon, J Konc, M Ali, VR Chowdhury, P Sormanni, G Bernardes
(2024)
Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases
DJ Rinauro, F Chiti, M Vendruscolo, R Limbocker
– Molecular Neurodegeneration
(2024)
19,
20
Large-scale visualisation of α-synuclein oligomers in Parkinson’s disease brain tissue
R Andrews, B Fu, CE Toomey, JC Breiter, J Lachica, R Tian, JS Beckwith, L-M Needham, GJ Chant, C Loiseau, A Deconfin, K Baspin, PJ Magill, Z Jaunmuktane, OJ Freeman, BJM Taylor, J Hardy, T Lashley, M Ryten, M Vendruscolo, NW Wood, LE Weiss, S Gandhi, SF Lee
(2024)
Modulation of α-synuclein in vitro aggregation kinetics by its alternative splice isoforms.
A Röntgen, Z Toprakcioglu, JE Tomkins, M Vendruscolo
– Proceedings of the National Academy of Sciences
(2024)
121,
e2313465121
Maturation-dependent changes in the size, structure and seeding capacity of Aβ42 amyloid fibrils
A Miller, S Chia, E Klimont, TPJ Knowles, M Vendruscolo, FS Ruggeri
– Communications Biology
(2024)
7,
153
Sequence-Based Drug Design Using Transformers
M Vendruscolo, S Zhang, D Huo, R Horne, Y Qi, SP Ojeda, A Yan
(2024)
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Co-Director

Research Interest Groups

Telephone number

01223 763873

Email address