Professor Michele Vendruscolo

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

Erratum to: The molecular chaperones DNAJB6 and Hsp70 cooperate to suppress α-synuclein aggregation (Scientific Reports, (2017), 7, 1, (9039), 10.1038/s41598-017-08324-z)

FA Aprile, E Källstig, G Limorenko, M Vendruscolo, D Ron, C Hansen

– Scientific reports

(2018)

11848

(DOI: 10.1038/s41598-018-29893-7)

Structural differences between toxic and nontoxic HypF-N oligomers

C Capitini, JR Patel, A Natalello, C D'Andrea, A Relini, JA Jarvis, L Birolo, A Peduzzo, M Vendruscolo, P Matteini, CM Dobson, A De Simone, F Chiti

– Chemical communications (Cambridge, England)

(2018)

54,

8637

(DOI: 10.1039/c8cc03446j)

Stabilization and Characterization of Cytotoxic Aβ40 Oligomers Isolated from an Aggregation Reaction in the Presence of Zinc Ions.

B Mannini, J Habchi, S Chia, FS Ruggeri, M Perni, TPJ Knowles, CM Dobson, M Vendruscolo

– ACS Chemical Neuroscience

(2018)

(DOI: 10.1021/acschemneuro.8b00141)

Structural Ensemble Modulation upon Small-Molecule Binding to Disordered Proteins.

GT Heller, M Bonomi, M Vendruscolo

– Journal of molecular biology

(2018)

430,

2288

(DOI: 10.1016/j.jmb.2018.03.015)

Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery

M Perni, PK Challa, JB Kirkegaard, R Limbocker, M Koopman, MC Hardenberg, P Sormanni, T Müller, KL Saar, LWY Roode, J Habchi, G Vecchi, N Fernando, S Casford, EAA Nollen, M Vendruscolo, CM Dobson, TPJ Knowles

– J Neurosci Methods

(2018)

306,

(DOI: 10.1016/j.jneumeth.2018.02.005)

Determination of the conformational states of strychnine in solution using NMR residual dipolar couplings in a tensor-free approach.

G Tomba, C Camilloni, M Vendruscolo

– Methods

(2018)

(DOI: 10.1016/j.ymeth.2018.07.005)

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

M Perni, P Flagmeier, R Limbocker, R Cascella, FA Aprile, C Galvagnion, GT Heller, G Meisl, SW Chen, JR Kumita, PK Challa, JB Kirkegaard, SIA Cohen, B Mannini, D Barbut, EAA Nollen, C Cecchi, N Cremades, TPJ Knowles, F Chiti, M Zasloff, M Vendruscolo, CM Dobson

– ACS Chem Biol

(2018)

(DOI: 10.1021/acschembio.8b00466)