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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

Molecular dynamics simulations with replica-averaged structural restraints generate structural ensembles according to the maximum entropy principle (vol 138, 094112, 2013)
A Cavalli, C Camilloni, M Vendruscolo
– J Chem Phys
(2013)
139,
169903
(doi: 10.1063/1.4828456)
pE-DB: a database of structural ensembles of intrinsically disordered and of unfolded proteins.
M Varadi, S Kosol, P Lebrun, E Valentini, M Blackledge, AK Dunker, IC Felli, JD Forman-Kay, RW Kriwacki, R Pierattelli, J Sussman, DI Svergun, VN Uversky, M Vendruscolo, D Wishart, PE Wright, P Tompa
– Nucleic Acids Res
(2013)
42,
d326
(doi: 10.1093/nar/gkt960)
Cucurbit[8]uril and blue-box: High-energy water release overwhelms electrostatic interactions
F Biedermann, M Vendruscolo, OA Scherman, A De Simone, WM Nau
– J Am Chem Soc
(2013)
135,
14879
(doi: 10.1021/ja407951x)
Subdomain Architecture and Stability of a Giant Repeat Protein
M Tsytlonok, P Sormanni, PJE Rowling, M Vendruscolo, LS Itzhaki
– Journal of Physical Chemistry B
(2013)
117,
13029
(doi: 10.1021/jp402360x)
Structures of the Excited States of Phospholamban and Shifts in Their Populations upon Phosphorylation
A De Simone, M Gustavsson, RW Montalvao, L Shi, G Veglia, M Vendruscolo
– Biochemistry
(2013)
52,
6684
(doi: 10.1021/bi400517b)
A relationship between the aggregation rates of α-synuclein variants and the β-sheet populations in their monomeric forms
C Camilloni, M Vendruscolo
– The journal of physical chemistry. B
(2013)
117,
10737
(doi: 10.1021/jp405614j)
Characterization of the interdomain motions in hen lysozyme using residual dipolar couplings as replica-averaged structural restraints in molecular dynamics simulations
A De Simone, RW Montalvao, CM Dobson, M Vendruscolo
– Biochemistry
(2013)
52,
6480
(doi: 10.1021/bi4007513)
In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-synuclein within E. coli cells.
CA Waudby, C Camilloni, AWP Fitzpatrick, LD Cabrita, CM Dobson, M Vendruscolo, J Christodoulou
– PLoS One
(2013)
8,
e72286
(doi: 10.1371/journal.pone.0072286)
Nanobodies raised against monomeric α-synuclein distinguish between fibrils at different maturation stages
T Guilliams, F El-Turk, AK Buell, EM O'Day, FA Aprile, EK Esbjörner, M Vendruscolo, N Cremades, E Pardon, L Wyns, ME Welland, J Steyaert, J Christodoulou, CM Dobson, E De Genst
– Journal of Molecular Biology
(2013)
425,
2397
(doi: 10.1016/j.jmb.2013.01.040)
Identification of small-molecule binding pockets in the soluble monomeric form of the Aβ42 peptide
M Zhu, A De Simone, D Schenk, G Toth, CM Dobson, M Vendruscolo
– The Journal of chemical physics
(2013)
139,
035101
(doi: 10.1063/1.4811831)
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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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