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Yusuf Hamied Department of Chemistry

 

Professor Michele Vendruscolo

Portrait of mv245

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

A Brain-Permeable Aminosterol Regulates Cell Membranes to Mitigate the Toxicity of Diverse Pore-Forming Agents
RP Kreiser, AK Wright, LR Sasser, DJ Rinauro, JM Gabriel, CM Hsu, JA Hurtado, TL McKenzie, S Errico, JA Albright, L Richardson, VA Jaffett, DE Riegner, LT Nguyen, K LeForte, M Zasloff, JE Hollows, F Chiti, M Vendruscolo, R Limbocker
– ACS chemical neuroscience
(2022)
13,
1219
(DOI: 10.1021/acschemneuro.1c00840)
Sequence Determinants of the Aggregation of Proteins Within Condensates Generated by Liquid-liquid Phase Separation.
M Vendruscolo, M Fuxreiter
– Journal of Molecular Biology
(2022)
434,
167201
(DOI: 10.1016/j.jmb.2021.167201)
Kinetic profiling of therapeutic strategies for inhibiting the formation of amyloid oligomers.
TCT Michaels, AJ Dear, SIA Cohen, M Vendruscolo, TPJ Knowles
– The Journal of chemical physics
(2022)
156,
164904
(DOI: 10.1063/5.0077609)
Squalamine and trodusquemine: two natural products for neurodegenerative diseases, from physical chemistry to the clinic
R Limbocker, S Errico, D Barbut, TPJ Knowles, M Vendruscolo, F Chiti, M Zasloff
– Natural Product Reports: a journal of current development in bioorganic chemistry
(2022)
39,
742
(DOI: 10.1039/d1np00042j)
Common sequence motifs of nascent chains engage the ribosome surface and trigger factor.
A Deckert, AME Cassaignau, X Wang, T Włodarski, SHS Chan, CA Waudby, JP Kirkpatrick, M Vendruscolo, LD Cabrita, J Christodoulou
– Proc Natl Acad Sci U S A
(2021)
118,
e2103015118
(DOI: 10.1073/pnas.2103015118)
Identification of a Thyroid Hormone Derivative as a Pleiotropic Agent for the Treatment of Alzheimer's Disease.
M Runfola, M Perni, X Yang, M Marchese, A Bacci, S Mero, FM Santorelli, B Polini, G Chiellini, D Giuliani, A Vilella, M Bodria, E Daini, E Vandini, S Rudge, S Gul, MOJ Wakelam, M Vendruscolo, S Rapposelli
– Pharmaceuticals (Basel, Switzerland)
(2021)
14,
1330
(DOI: 10.3390/ph14121330)
Neuroserpin and transthyretin are extracellular chaperones that preferentially inhibit amyloid formation.
J West, S Satapathy, DR Whiten, M Kelly, NJ Geraghty, E-J Proctor, P Sormanni, M Vendruscolo, JN Buxbaum, M Ranson, MR Wilson
– Sci Adv
(2021)
7,
eabf7606
(DOI: 10.1126/sciadv.abf7606)
A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
F Brotzakis, P Lindstedt, R Taylor, G Bernardes, M Vendruscolo
– ACS Central Science
(2021)
(DOI: 10.21203/rs.3.rs-215084/v1)
A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms.
ZF Brotzakis, PR Lindstedt, RJ Taylor, DJ Rinauro, NCT Gallagher, GJL Bernardes, M Vendruscolo
– ACS Central Science
(2021)
7,
1986
(DOI: 10.1021/acscentsci.1c00585)
Proliferation of Tau 304–380 Fragment Aggregates through Autocatalytic Secondary Nucleation
DC Rodriguez Camargo, E Sileikis, S Chia, E Axell, K Bernfur, RL Cataldi, SIA Cohen, G Meisl, J Habchi, TPJ Knowles, M Vendruscolo, S Linse
– ACS Chem Neurosci
(2021)
12,
4406
(DOI: 10.1021/acschemneuro.1c00454)
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Telephone number

01223 763873

Email address

mv245@cam.ac.uk

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