Professor Michele Vendruscolo University positionProfessor Professor Michele Vendruscolo is pleased to consider applications from prospective PhD students. DepartmentsInstitutesCentre for Misfolding Diseases Home pagehttp://www-vendruscolo.ch.cam.ac.uk/ Research ThemesInterestsOur research at the Centre for Misfolding Diseases (https://www.cmd.ch.cam.ac.uk/) is aimed at understanding the molecular origins of neurodegenerative disorders. 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 protein homeostasis and its association with ageing and neurodegenerative disorders.  Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. View image full-size (1653x1602 pixels) Research Focus
EquipmentCell culture Computational modelling Confocal microscopy Fluorescence microscopy Immunohistochemistry Microscopy Protein purification Recombinant protein expression Collaborators
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Key publicationsCohen SI, Arosio P, Presto J, Kurudenkandy FR, Biverstål H, Dolfe L, Dunning C, Yang X, Frohm B, Vendruscolo M, Johansson J, Dobson CM, Fisahn A, Knowles TP, Linse S. (2015), “A molecular chaperone breaks the catalytic cycle that generates toxic A? oligomers” Nat. Struct. Mol. Biol. 22(3): 207-213 Murakami T, Qamar S, Lin JQ, Schierle GS, Rees E, Miyashita A, Costa AR, Dodd RB, Chan FT, Michel CH, Kronenberg-Versteeg D, Li Y, Yang SP, Wakutani Y, Meadows W, Ferry RR, Dong L, Tartaglia GG, Favrin G, Lin WL, Dickson DW, Zhen M, Ron D, Schmitt-Ulms G, Fraser PE, Shneider NA, Holt C, Vendruscolo M, Kaminski CF, St George-Hyslop P. (2015), “ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function.” Neuron Nov 18;88(4): 678-690 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 Publications2015Galvagnion C, Buell AK, Meisl G, Michaels TC, Vendruscolo M, Knowles TP, Dobson CM. (2015), “Lipid vesicles trigger ?-synuclein aggregation by stimulating primary nucleation” Nat. Chem. Biol. 11(3): 229-234 2014Arosio 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 ?-Synuclein by Small Molecules as a Potential Therapeutic Strategy for Parkinson's Disease.” PLoS One 9(2):e87133 Details 2013Cohen SI, Linse S, Luheshi LM, Hellstrand E, White DA, Rajah L, Otzen DE, Vendruscolo M, Dobson CM, Knowles TP (2013), “Proliferation of amyloid-?42 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-? amyloid fibril.” Proc Natl Acad Sci U S A 110(14):5468-73 Details 2012Neudecker 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 2011Baldwin 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 |
