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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

Systematic Activity Maturation of a Single-Domain Antibody with Non-canonical Amino Acids through Chemical Mutagenesis
PR Lindstedt, FA Aprile, P Sormanni, R Rakoto, CM Dobson, GJL Bernardes, M Vendruscolo
– Cell Chemical Biology
(2020)
28,
70
(doi: 10.1016/j.chembiol.2020.11.002)
Biophysical studies of protein misfolding and aggregation in in vivo models of Alzheimer's and Parkinson's diseases (vol 53, 1, 2020)
T Sinnige, K Stroobants, CM Dobson, M Vendruscolo
– Quarterly reviews of biophysics
(2020)
53,
e13
(doi: 10.1017/S0033583520000104)
Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers
RP Kreiser, AK Wright, NR Block, JE Hollows, LT Nguyen, K LeForte, B Mannini, M Vendruscolo, R Limbocker
– International journal of molecular sciences
(2020)
21,
E8651
(doi: 10.3390/ijms21228651)
A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms
F Brotzakis, P Lindstedt, R Taylor, G Bernardes, M Vendruscolo
– biorxiv
(2020)
2020.11.10.376285
(doi: 10.1101/2020.11.10.376285)
Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer's disease
GT Heller, FA Aprile, TCT Michaels, R Limbocker, M Perni, FS Ruggeri, B Mannini, T Löhr, M Bonomi, C Camilloni, A De Simone, IC Felli, R Pierattelli, TPJ Knowles, CM Dobson, M Vendruscolo
– Science Advances
(2020)
6,
eabb5924
(doi: 10.1126/SCIADV.ABB5924)
Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage <i>in vitro</i>.
D Frankel, M Davies, B Bhushan, Y Kulaberoglu, P Urriola-Munoz, J Bertrand-Michel, MR Pergande, AA Smith, S Preet, TJ Park, M Vendruscolo, KS Rankin, SM Cologna, JR Kumita, N Cenac, E St John Smith
– Aging
(2020)
12,
22266
(doi: 10.18632/aging.202138)
The Hsc70 Disaggregation Machinery Removes Monomer Units Directly from α-Synuclein Fibril Ends
M Schneider, S Gautam, T Herling, E Andrzejewska, G Krainer, A Miller, Q Peter, FS Ruggeri, M Vendruscolo, A Bracher, C Dobson, U Hartl, T Knowles
(2020)
2020.11.02.365825
(doi: 10.1101/2020.11.02.365825)
An intrinsically disordered motif regulates the interaction between the p47 adaptor and the p97 AAA+ ATPase.
AE Conicella, R Huang, ZA Ripstein, A Nguyen, E Wang, T Löhr, P Schuck, M Vendruscolo, JL Rubinstein, LE Kay
– Proc Natl Acad Sci U S A
(2020)
117,
26226
(doi: 10.1073/pnas.2013920117)
Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies.
S Linse, T Scheidt, K Bernfur, M Vendruscolo, CM Dobson, SIA Cohen, E Sileikis, M Lundqvist, F Qian, T O'Malley, T Bussiere, PH Weinreb, CK Xu, G Meisl, SRA Devenish, TPJ Knowles, O Hansson
– Nature Structural and Molecular Biology
(2020)
27,
1125
(doi: 10.1038/s41594-020-0505-6)
A rationally designed bicyclic peptide remodels Aβ42 aggregation in vitro and reduces its toxicity in a worm model of Alzheimer's disease
T Ikenoue, FA Aprile, P Sormanni, FS Ruggeri, M Perni, GT Heller, CP Haas, C Middel, R Limbocker, B Mannini, TCT Michaels, TPJ Knowles, CM Dobson, M Vendruscolo
– Scientific reports
(2020)
10,
15280
(doi: 10.1038/s41598-020-69626-3)
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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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