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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

Reversible inhibition of the ClpP protease via an N-terminal conformational switch.
S Vahidi, ZA Ripstein, M Bonomi, T Yuwen, MF Mabanglo, JB Juravsky, K Rizzolo, A Velyvis, WA Houry, M Vendruscolo, JL Rubinstein, LE Kay
– Proceedings of the National Academy of Sciences of the United States of America
(2018)
115,
E6447
(doi: 10.1073/pnas.1805125115)
Cooperative Assembly of Hsp70 Subdomain Clusters.
MA Wright, FA Aprile, MMJ Bellaiche, TCT Michaels, T Müller, P Arosio, M Vendruscolo, CM Dobson, TPJ Knowles
– Biochemistry
(2018)
57,
3641
(doi: 10.1021/acs.biochem.8b00151)
A rationally designed Hsp70 variant rescues the aggregation-associated toxicity of human IAPP in cultured pancreatic islet β-cells
MN Bongiovanni, FA Aprile, P Sormanni, M Vendruscolo
– International Journal of Molecular Sciences
(2018)
(doi: 10.3390/ijms19051443)
A rationally designed Hsp70 variant rescues the aggregation-associated toxicity of human IAPP in cultured pancreatic islet β-cells
MN Bongiovanni, FA Aprile, P Sormanni, M Vendruscolo
– International journal of molecular sciences
(2018)
19,
1443
(doi: 10.3390/ijms19051443)
Developing NMR methods for macromolecular machines: Measurement of residual dipolar couplings to probe dynamic regions of the ribosome
X Wang, J Kirkpatrick, H Launay, A de Simone, D Häussinger, C Dobson, M Vendruscolo, L Cabrita, C Waudby, J Christodoulou
(2018)
319251
(doi: 10.1101/319251)
Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes.
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
– Nat Chem
(2018)
10,
673
(doi: 10.1038/s41557-018-0031-x)
Phase Separation of FUS is Modulated by Methylation State of Cation-π Interactions and Interaction with TNPO1
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
– Cell
(2018)
(doi: 10.1016/j.cell.2018.03.056)
FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-π Interactions.
S Qamar, G Wang, SJ Randle, FS Ruggeri, JA Varela, JQ Lin, EC Phillips, A Miyashita, D Williams, F Ströhl, W Meadows, R Ferry, VJ Dardov, GG Tartaglia, LA Farrer, GS Kaminski Schierle, CF Kaminski, CE Holt, PE Fraser, G Schmitt-Ulms, D Klenerman, T Knowles, M Vendruscolo, P St George-Hyslop
– Cell
(2018)
173,
720
(doi: 10.1016/j.cell.2018.03.056)
Parapred: Antibody paratope prediction using convolutional and recurrent neural networks
E Liberis, P Velickovic, P Sormanni, M Vendruscolo, P Liò
– Bioinformatics (Oxford, England)
(2018)
34,
2944
(doi: 10.1093/bioinformatics/bty305)
Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy.
M Bonomi, R Pellarin, M Vendruscolo
– Biophysical journal
(2018)
114,
1604
(doi: 10.1016/j.bpj.2018.02.028)
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Research Groups

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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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