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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

The αC-β4 loop controls the allosteric cooperativity between nucleotide and substrate in the catalytic subunit of protein kinase A
C Olivieri, Y Wang, C Walker, MV Subrahmanian, KN Ha, D Bernlohr, J Gao, C Camilloni, M Vendruscolo, SS Taylor, G Veglia
– eLife
(2024)
12,
(doi: 10.7554/elife.91506.3)
The αC-β4 loop controls the allosteric cooperativity between nucleotide and substrate in the catalytic subunit of protein kinase A.
C Olivieri, Y Wang, C Walker, MV Subrahmanian, KN Ha, D Bernlohr, J Gao, C Camilloni, M Vendruscolo, SS Taylor, G Veglia
– Elife
(2024)
12,
rp91506
(doi: 10.7554/eLife.91506)
Identification of high-affinity secondary nucleation inhibitors of Aβ42 aggregation from an ultra-large chemical library using Deep Docking
M Vendruscolo, M Brezinova, F Brotzakis, R Horne, VR Chowdhury, R Gregory, F Gentile
(2024)
(doi: 10.21203/rs.3.rs-4512167/v1)
The diversity ofSNCAtranscripts in neurons, and its impact on antisense oligonucleotide therapeutics
JR Evans, EK Gustavsson, I Doykov, D Murphy, GS Virdi, J Lachica, A Röntgen, MH Murtada, CW Pang, H Macpherson, AI Wernick, CE Toomey, D Athauda, ML Choi, J Hardy, NW Wood, M Vendruscolo, K Mills, W Heywood, M Ryten, S Gandhi
(2024)
(doi: 10.1101/2024.05.30.596437)
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
– Nature Communications
(2024)
15,
3835
(doi: 10.1038/s41467-024-47585-x)
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
– Nat Chem Biol
(2024)
20,
634
(doi: 10.1038/s41589-024-01580-x)
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
(doi: 10.1021/acs.jpcb.4c00174)
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 Chem Neurosci
(2024)
15,
1125
(doi: 10.1021/acschemneuro.3c00718)
Targeted protein editing with an antibody-based system
M Vendruscolo, O Rimon, J Konc, M Ali, VR Chowdhury, P Sormanni, G Bernardes
(2024)
(doi: 10.21203/rs.3.rs-3947849/v1)
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
(doi: 10.1186/S13024-023-00651-2)
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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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