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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

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
– Nature Communications
(2019)
10,
1541
(doi: 10.1038/s41467-019-09477-3)
The metastability of the proteome of spinal motor neurons underlies their selective vulnerability in ALS
JJ Yerbury, L Ooi, IP Blair, P Ciryam, CM Dobson, M Vendruscolo
– Neurosci Lett
(2019)
704,
89
(doi: 10.1016/j.neulet.2019.04.001)
A method of predicting the in vitro fibril formation propensity of Aβ40 mutants based on their inclusion body levels in E. coli.
K Sanagavarapu, E Nüske, I Nasir, G Meisl, JN Immink, P Sormanni, M Vendruscolo, TPJ Knowles, A Malmendal, C Cabaleiro-Lago, S Linse
– Scientific Reports
(2019)
9,
3680
(doi: 10.1038/s41598-019-39216-z)
Atomic force microscopy for single molecule characterisation of protein aggregation
FS Ruggeri, T Šneideris, M Vendruscolo, TPJ Knowles
– Archives of Biochemistry and Biophysics
(2019)
664,
134
(doi: 10.1016/j.abb.2019.02.001)
A superposition free method for protein conformational ensemble analyses and local clustering based on a differential geometry representation of backbone
AM da Silva Neto, SR Silva, M Vendruscolo, C Camilloni, RW Montalvão
– Proteins Structure Function and Bioinformatics
(2019)
87,
302
(doi: 10.1002/prot.25652)
Structure and Dynamics of Alzheimer's Associated Amyloid-Beta Peptide
T Lohr, K Kohlhoff, G Heller, M Vendruscolo
– Biophysical Journal
(2019)
116,
437a
(doi: 10.1016/j.bpj.2018.11.2352)
Probing Specificity in Disordered Protein Interactions with Small Molecules using Integrative Methods
GT Heller, FA Aprile, M Bonomi, C Camilloni, A De Simone, M Vendruscolo
– Biophysical Journal
(2019)
116,
180a
(doi: 10.1016/j.bpj.2018.11.998)
Targeting the Formation of Amyloid Oligomers using Rationally Designed Antibodies
FA Aprile, P Sormanni, M Perni, P Arosio, S Linse, TP Knowles, CM Dobson, M Vendruscolo
– Biophysical Journal
(2019)
116,
28a
(doi: 10.1016/j.bpj.2018.11.196)
In vitro and in silico assessment of the developability of a designed monoclonal antibody library.
A-M Wolf Pérez, P Sormanni, JS Andersen, LI Sakhnini, I Rodriguez-Leon, JR Bjelke, AJ Gajhede, L De Maria, DE Otzen, M Vendruscolo, N Lorenzen
– Mabs
(2019)
11,
388
(doi: 10.1080/19420862.2018.1556082)
Chemical and mechanistic analysis of photodynamic inhibition of Alzheimer's β-amyloid aggregation.
M Ahn, BI Lee, S Chia, J Habchi, JR Kumita, M Vendruscolo, CM Dobson, CB Park
– Chem Commun (Camb)
(2019)
55,
1152
(doi: 10.1039/c8cc09288e)
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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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