Professor Michele Vendruscolo

Michele Vendruscolo

University position

Professor

Professor Michele Vendruscolo is pleased to consider applications from prospective PhD students.

Departments

Department of Chemistry

Email

mv245@cam.ac.uk

Home page

http://www-vendruscolo.ch.cam.ac.uk/index.html

Research Theme

Systems and Computational Neuroscience

Interests

Our research is aimed at understanding the principles governing protein homeostasis - the ability of cells to generate and regulate the levels of proteins in terms of conformations, interactions, concentrations and cellular localisation. We have set up an interdisciplinary programme that brings together methods and concepts from chemistry, physics, engineering, genetics and medicine. We are using a combination of in vitro, in silico and in vivo approaches to study protein homeostasis through the analysis of the effects that result from its alteration in specific proteins, from either amino acid mutations, or changes in concentration and solubility, or the interactions with other molecules. This programme is generating new insights into the mechanism through which physical and chemical sciences can increase our understanding of the nature and consequences of the failure to maintain homeostasis, which is associated with such phenomena as ageing and neurodegenerative disorders.

Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins.
Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins.
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Research Focus

Keywords

amyloid

protein aggregation

computational methods

Clinical conditions

Alzheimer's disease

Parkinson's disease

Equipment

Computational modelling

Collaborators

Cambridge

Christopher Dobson

Clemens Kaminski

Tuomas Knowles

Peter St George-Hyslop

International

Fabrizio Chiti Web: http://www.fabriziochiti.it/

Rick Morimoto Web: http://groups.molbiosci.northwestern.edu/morimoto/

Key publications

Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, Vendruscolo M (2013), “Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins.” Cell Rep 5(3):781-90 Details

Tartaglia GG, Pawar AP, Campioni S, Dobson CM, Chiti F, Vendruscolo M (2008), “Prediction of aggregation-prone regions in structured proteins.” J Mol Biol 380(2):425-36 Details

Tartaglia GG, Pechmann S, Dobson CM and Vendruscolo M (2007), “Life on the Edge: A link between gene expression levels and aggregation rates of human proteins” Trends Biochem Sci 32:204-206 Details

Publications

2014

Arosio P, Vendruscolo M, Dobson CM, Knowles TP (2014), “Chemical kinetics for drug discovery to combat protein aggregation diseases.” Trends Pharmacol Sci Details

Tóth G, Gardai SJ, Zago W, Bertoncini CW, Cremades N, Roy SL, Tambe MA, Rochet JC, Galvagnion C, Skibinski G, Finkbeiner S, Bova M, Regnstrom K, Chiou SS, Johnston J, Callaway K, Anderson JP, Jobling MF, Buell AK, Yednock TA, Knowles TP, Vendruscolo M, Christodoulou J, Dobson CM, Schenk D, McConlogue L (2014), “Targeting the Intrinsically Disordered Structural Ensemble of α-Synuclein by Small Molecules as a Potential Therapeutic Strategy for Parkinson's Disease.” PLoS One 9(2):e87133 Details

2013

Cohen SI, Linse S, Luheshi LM, Hellstrand E, White DA, Rajah L, Otzen DE, Vendruscolo M, Dobson CM, Knowles TP (2013), “Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism.” Proc Natl Acad Sci U S A 110(24):9758-63 Details

Fitzpatrick AW, Debelouchina GT, Bayro MJ, Clare DK, Caporini MA, Bajaj VS, Jaroniec CP, Wang L, Ladizhansky V, Müller SA, MacPhee CE, Waudby CA, Mott HR, De Simone A, Knowles TP, Saibil HR, Vendruscolo M, Orlova EV, Griffin RG, Dobson CM (2013), “Atomic structure and hierarchical assembly of a cross-β amyloid fibril.” Proc Natl Acad Sci U S A 110(14):5468-73 Details

2012

Neudecker P, Robustelli P, Cavalli A, Walsh P, Lundström P, Zarrine-Afsar A, Sharpe S, Vendruscolo M, Kay LE (2012), “Structure of an intermediate state in protein folding and aggregation.” Science 336(6079):362-6 Details

Vendruscolo M (2012), “Proteome folding and aggregation.” Curr Opin Struct Biol 22(2):138-43 Details

2011

Baldwin AJ, Knowles TP, Tartaglia GG, Fitzpatrick AW, Devlin GL, Shammas SL, Waudby CA, Mossuto MF, Meehan S, Gras SL, Christodoulou J, Anthony-Cahill SJ, Barker PD, Vendruscolo M, Dobson CM (2011), “Metastability of native proteins and the phenomenon of amyloid formation.” J Am Chem Soc 133(36):14160-3 Details

Olzscha H, Schermann SM, Woerner AC, Pinkert S, Hecht MH, Tartaglia GG, Vendruscolo M, Hayer-Hartl M, Hartl FU, Vabulas RM (2011), “Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions.” Cell 144(1):67-78 Details