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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 RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage
J Kitevski-LeBlanc, A Fradet-Turcotte, P Kukic, MD Wilson, G Portella, T Yuwen, S Panier, S Duan, MD Canny, H van Ingen, CH Arrowsmith, JL Rubinstein, M Vendruscolo, D Durocher, LE Kay
– eLife
(2017)
6,
e23872
(doi: 10.7554/eLife.23872)
Emergence and evolution of an interaction between intrinsically disordered proteins.
G Hultqvist, E Åberg, C Camilloni, GN Sundell, E Andersson, J Dogan, CN Chi, M Vendruscolo, P Jemth
– Elife
(2017)
6,
e16059
(doi: 10.7554/eLife.16059)
Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS
P Ciryam, IA Lambert-Smith, DM Bean, R Freer, F Cid, GG Tartaglia, DN Saunders, MR Wilson, SG Oliver, RI Morimoto, CM Dobson, M Vendruscolo, G Favrin, JJ Yerbury
– Proc Natl Acad Sci U S A
(2017)
114,
e3935
(doi: 10.1073/pnas.1613854114)
MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions.
Y Yoshimura, MA Holmberg, P Kukic, CB Andersen, A Mata-Cabana, SF Falsone, M Vendruscolo, EAA Nollen, FAA Mulder
– The Journal of biological chemistry
(2017)
292,
8269
(doi: 10.1074/jbc.M116.764886)
Simultaneous quantification of protein order and disorder
P Sormanni, D Piovesan, GT Heller, M Bonomi, P Kukic, C Camilloni, M Fuxreiter, Z Dosztanyi, RV Pappu, MM Babu, S Longhi, P Tompa, AK Dunker, VN Uversky, SCE Tosatto, M Vendruscolo
– Nature Chemical Biology
(2017)
13,
339
(doi: 10.1038/nchembio.2331)
Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation
O Sin, T de Jong, A Mata-Cabana, M Kudron, MA Zaini, FA Aprile, RI Seinstra, E Stroo, RW Prins, CN Martineau, HH Wang, W Hogewerf, A Steinhof, EE Wanker, M Vendruscolo, CF Calkhoven, V Reinke, V Guryev, EAA Nollen
– Molecular cell
(2017)
65,
1096
(doi: 10.1016/j.molcel.2017.02.022)
Inhibition of α‑Synuclein Fibril Elongation by Hsp70 Is Governed by a Kinetic Binding Competition between α‑Synuclein Species
FA Aprile, P Arosio, G Fusco, SW Chen, JR Kumita, A Dhulesia, P Tortora, TPJ Knowles, M Vendruscolo, CM Dobson, N Cremades
– Biochemistry
(2017)
56,
1177
(doi: 10.1021/acs.biochem.6b01178)
A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity (vol 114, pg E1009, 2017)
M Perni, C Galvagnion, A Maltsev, G Meisl, MBD Mueller, PK Challa, JB Kirkegaard, P Flagmeier, SIA Cohen, R Cascella, SW Chen, R Limboker, P Sormanni, GT Heller, FA Aprile, N Cremades, C Cecchi, F Chiti, EAA Nollen, TPJ Knowles, M Vendruscolo, A Bax, M Zasloff, CM Dobson
– Proceedings of the National Academy of Sciences
(2017)
114,
e2543
(doi: 10.1073/pnas.1701964114)
Bayesian weighing of electron cryo-microscopy data for integrative structural modeling
M Bonomi, S Hanot, C Greenberg, A Sali, M Nilges, M Vendruscolo, R Pellarin
(2017)
113951
(doi: 10.1101/113951)
Widespread Proteome Remodeling and Aggregation in Aging C. elegans.
DM Walther, P Kasturi, M Zheng, S Pinkert, G Vecchi, P Ciryam, RI Morimoto, CM Dobson, M Vendruscolo, M Mann, FU Hartl
– Cell
(2017)
168,
944
(doi: 10.1016/j.cell.2016.12.041)
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Research Groups

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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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