Centre for Misfolding Diseases

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

In vivo translation rates can substantially delay the cotranslational folding of the Escherichia coli cytosolic proteome
P Ciryam, RI Morimoto, M Vendruscolo, CM Dobson, EP O'Brien
Proc Natl Acad Sci U S A
(2012)
110
(doi: 10.1073/pnas.1213624110)
A rationally designed six-residue swap generates comparability in the aggregation behavior of α-synuclein and β-synuclein.
C Roodveldt, A Andersson, EJ De Genst, A Labrador-Garrido, AK Buell, CM Dobson, GG Tartaglia, M Vendruscolo
Biochemistry
(2012)
51
(doi: 10.1021/bi300558q)
Twisting transition between crystalline and fibrillar phases of aggregated peptides
TPJ Knowles, A De Simone, AW Fitzpatrick, A Baldwin, S Meehan, L Rajah, M Vendruscolo, ME Welland, CM Dobson, EM Terentjev
Physical Review Letters
(2012)
109
(doi: 10.1103/PhysRevLett.109.158101)
In support of the BMRB
JL Markley, H Akutsu, T Asakura, M Baldus, R Boelens, A Bonvin, R Kaptein, A Bax, I Bezsonova, MR Gryk, JC Hoch, DM Korzhnev, MW Maciejewski, D Case, WJ Chazin, TA Cross, S Dames, H Kessler, O Lange, T Madl, B Reif, M Sattler, D Eliezer, A Fersht, J Forman-Kay, LE Kay, J Fraser, J Gross, T Kortemme, A Sali, T Fujiwara, K Gardner, X Luo, J Rizo-Rey, M Rosen, RR Gil, C Ho, G Rule, AM Gronenborn, R Ishima, J Klein-Seetharaman, P Tang, P van der Wel, Y Xu, S Grzesiek, S Hiller, J Seelig, ED Laue, H Mott, D Nietlispach, I Barsukov, L-Y Lian, D Middleton, T Blumenschein, G Moore, I Campbell, J Schnell, IJ Vakonakis, A Watts, MR Conte, J Mason, M Pfuhl, MR Sanderson, J Craven, M Williamson, C Dominguez, G Roberts, U Günther, M Overduin, J Werner, P Williamson, C Blindauer, M Crump, P Driscoll, T Frenkiel, A Golovanov, S Matthews, J Parkinson, D Uhrin, M Williams, D Neuhaus, H Oschkinat, A Ramos, DE Shaw, C Steinbeck, M Vendruscolo, GW Vuister, KJ Walters, H Weinstein, K Wüthrich, S Yokoyama
Nature Structural Molecular Biology
(2012)
19
(doi: 10.1038/nsmb.2371)
From macroscopic measurements to microscopic mechanisms of protein aggregation
SIA Cohen, M Vendruscolo, CM Dobson, TPJ Knowles
Journal of Molecular Biology
(2012)
421
(doi: 10.1016/j.jmb.2012.02.031)
Sequence-based prediction of protein solubility
F Agostini, M Vendruscolo, GG Tartaglia
Journal of Molecular Biology
(2012)
421
(doi: 10.1016/j.jmb.2011.12.005)
ADP ribosylation adapts an ER chaperone response to short-term fluctuations in unfolded protein load
JE Chambers, K Petrova, G Tomba, M Vendruscolo, D Ron
Journal of Cell Biology
(2012)
198
(doi: 10.1083/jcb.201202005)
Determination of structural fluctuations of proteins from structure-based calculations of residual dipolar couplings
RW Montalvao, A De Simone, M Vendruscolo
Journal of Biomolecular NMR
(2012)
53
(doi: 10.1007/s10858-012-9644-3)
Trigger factor slows co-translational folding through kinetic trapping while sterically protecting the nascent chain from aberrant cytosolic interactions.
EP O'Brien, J Christodoulou, M Vendruscolo, CM Dobson
J Am Chem Soc
(2012)
134
(doi: 10.1021/ja302305u)
Prediction of variable translation rate effects on cotranslational protein folding.
EP O'Brien, M Vendruscolo, CM Dobson
Nat Commun
(2012)
3
(doi: 10.1038/ncomms1850)

Co-Director

Research Interest Groups

Telephone number

01223 763873

Email address

mv245@cam.ac.uk
Yusuf Hamied Department of Chemistry
Lensfield Road
Cambridge
CB2 1EW
T: +44 (0) 1223 336300
enquiries@ch.cam.ac.uk
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