Professor Michele Vendruscolo
Professor Michele Vendruscolo is pleased to consider applications from prospective PhD students.
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.
Fabrizio Chiti Web: http://www.fabriziochiti.it/
Rick Morimoto Web: http://groups.molbiosci.northwestern.edu/morimoto/
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
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
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
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
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