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Department of Chemistry

 
Portrait of mv245

 

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.

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.

 

 

Publications

Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms
S De, DC Wirthensohn, P Flagmeier, C Hughes, FA Aprile, FS Ruggeri, DR Whiten, D Emin, Z Xia, JA Varela, P Sormanni, F Kundel, TPJ Knowles, CM Dobson, C Bryant, M Vendruscolo, D Klenerman
– Nat Commun
(2019)
10,
1541
The free energy landscape of the oncogene protein E7 of human papillomavirus type 16 reveals a complex interplay between ordered and disordered regions.
P Kukic, GM Lo Piccolo, MO Nogueira, DI Svergun, M Vendruscolo, IC Felli, R Pierattelli
– Scientific reports
(2019)
9,
5822
Trodusquemine enhances A beta(42) aggregation but suppresses its toxicity by displacing oligomers from cell membranes
R Limbocker, S Chia, FS Ruggeri, M Perni, R Cascella, GT Heller, G Meisl, B Mannini, J Habchi, TCT Michaels, PK Challa, M Ahn, ST Casford, N Fernando, CK Xu, ND Kloss, SIA Cohen, JR Kumita, C Cecchi, M Zasloff, S Linse, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson
– Nat Commun
(2019)
10,
225
Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons
MA Metrick, N do Carmo Ferreira, E Saijo, AG Hughson, A Kraus, C Orrú, MW Miller, G Zanusso, B Ghetti, M Vendruscolo, B Caughey
– Proc Natl Acad Sci U S A
(2019)
201909322
Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation
DC Delivoria, S Chia, J Habchi, M Perni, I Matis, N Papaevgeniou, M Reczko, N Chondrogianni, CM Dobson, M Vendruscolo, G Skretas
– Sci Adv
(2019)
5,
eaax5108
RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
Y-C Liao, MS Fernandopulle, G Wang, H Choi, L Hao, CM Drerup, R Patel, S Qamar, J Nixon-Abell, Y Shen, W Meadows, M Vendruscolo, TPJ Knowles, M Nelson, MA Czekalska, G Musteikyte, MA Gachechiladze, CA Stephens, HA Pasolli, LR Forrest, P St George-Hyslop, J Lippincott-Schwartz, ME Ward
– Cell
(2019)
179,
147
Probing the dynamic stalk region of the ribosome using solution NMR.
X Wang, JP Kirkpatrick, HMM Launay, A de Simone, D Häussinger, CM Dobson, M Vendruscolo, LD Cabrita, CA Waudby, J Christodoulou
– Sci Rep
(2019)
9,
13528
Characterizing Individual Protein Aggregates by Infrared Nanospectroscopy and Atomic Force Microscopy
FS Ruggeri, T Šneideris, S Chia, M Vendruscolo, TPJ Knowles
– Journal of visualized experiments : JoVE
(2019)
(DOI: 10.3791/60108)
Enhancement of the Anti-Aggregation Activity of a Molecular Chaperone Using a Rationally Designed Post-Translational Modification
PR Lindstedt, FA Aprile, MJ Matos, M Perni, JB Bertoldo, B Bernardim, Q Peter, G Jiménez-Osés, TPJ Knowles, CM Dobson, F Corzana, M Vendruscolo, GJL Bernardes
– ACS Central Science
(2019)
5,
1417
Small molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease
G Heller, F Aprile, T Michaels, R Limbocker, M Perni, FS Ruggeri, B Mannini, T Löhr, M Bonomi, A De Simone, I Felli, R Pierattelli, T Knowles, C Dobson, M Vendruscolo
(2019)
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Research Interest Groups

Telephone number

01223 763873

Email address

mv245@cam.ac.uk