Michele Vendruscolo

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. Perni M, Galvagnion C, Maltsev A, Meisl G, Müller M, Challa P, et al. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. Proc Natl Acad Sci U S A. 2017;114:E1009-E1017 pubmed publisher
    ..These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson's disease and related conditions. ..
  2. Borkar A, Vallurupalli P, Camilloni C, Kay L, Vendruscolo M. Simultaneous NMR characterisation of multiple minima in the free energy landscape of an RNA UUCG tetraloop. Phys Chem Chem Phys. 2017;19:2797-2804 pubmed publisher
    ..The approach that we present is general and can be applied to the study of the free energy landscapes of other RNA or RNA-protein systems. ..
  3. Habchi J, Chia S, Limbocker R, Mannini B, Ahn M, Perni M, et al. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease. Proc Natl Acad Sci U S A. 2017;114:E200-E208 pubmed publisher
    ..Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery. ..
  4. Boomsma W, Tian P, Frellsen J, Ferkinghoff Borg J, Hamelryck T, Lindorff Larsen K, et al. Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts. Proc Natl Acad Sci U S A. 2014;111:13852-7 pubmed publisher
  5. Kukić P, Lo Piccolo G, Nogueira M, Svergun D, Vendruscolo M, Felli I, et al. The free energy landscape of the oncogene protein E7 of human papillomavirus type 16 reveals a complex interplay between ordered and disordered regions. Sci Rep. 2019;9:5822 pubmed publisher
    ..These results provide compelling evidence of the complex conformational heterogeneity associated with the behaviour and interactions of this disordered protein associated with disease. ..
  6. De S, Wirthensohn D, Flagmeier P, Hughes C, Aprile F, Ruggeri F, et al. Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms. Nat Commun. 2019;10:1541 pubmed publisher
    ..These findings suggest that different toxic mechanisms driven by different soluble aggregated species of Aβ42 may contribute to the onset and progression of Alzheimer's disease. ..
  7. Limbocker R, Chia S, Ruggeri F, Perni M, Cascella R, Heller G, et al. Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes. Nat Commun. 2019;10:225 pubmed publisher
    ..The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD. ..
  8. Perni M, Casford S, Aprile F, Nollen E, Knowles T, Vendruscolo M, et al. Automated Behavioral Analysis of Large C. elegans Populations Using a Wide Field-of-view Tracking Platform. J Vis Exp. 2018;: pubmed publisher
  9. Fu H, Possenti A, Freer R, Nakano Y, Hernandez Villegas N, Tang M, et al. A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology. Nat Neurosci. 2019;22:47-56 pubmed publisher
    ..These results define a tau homeostasis signature that underlies the cellular and regional vulnerability of excitatory neurons to tau pathology. ..

More Information

Publications35

  1. Bonomi M, Vendruscolo M. Determination of protein structural ensembles using cryo-electron microscopy. Curr Opin Struct Biol. 2018;56:37-45 pubmed publisher
  2. Chia S, Habchi J, Michaels T, Cohen S, Linse S, Dobson C, et al. SAR by kinetics for drug discovery in protein misfolding diseases. Proc Natl Acad Sci U S A. 2018;115:10245-10250 pubmed publisher
    ..These results provide an initial demonstration of the potential of drug discovery strategies based on targeting directly the production of protein oligomers. ..
  3. Tomba G, Camilloni C, Vendruscolo M. Determination of the conformational states of strychnine in solution using NMR residual dipolar couplings in a tensor-free approach. Methods. 2018;148:4-8 pubmed publisher
    ..We illustrate the method in the case of strychnine, determining the three major conformational states of this small molecule and their associated occupation probabilities. ..
  4. Habchi J, Chia S, Galvagnion C, Michaels T, Bellaiche M, Ruggeri F, et al. Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes. Nat Chem. 2018;10:673-683 pubmed publisher
  5. Bongiovanni M, Aprile F, Sormanni P, Vendruscolo M. A Rationally Designed Hsp70 Variant Rescues the Aggregation-Associated Toxicity of Human IAPP in Cultured Pancreatic Islet ?-Cells. Int J Mol Sci. 2018;19: pubmed publisher
  6. Cavalli A, Vendruscolo M. Analysis of the performance of the CHESHIRE and YAPP methods at CASD-NMR round 3. J Biomol NMR. 2015;62:503-9 pubmed publisher
    ..6 Ã…. Taken together, these results illustrate how the NOESY based YAPP method and the chemical shift based CHESHIRE method can provide structures of comparable quality. ..
  7. Sormanni P, Aprile F, Vendruscolo M. The CamSol method of rational design of protein mutants with enhanced solubility. J Mol Biol. 2015;427:478-90 pubmed publisher
  8. Heller G, Bonomi M, Vendruscolo M. Structural Ensemble Modulation upon Small-Molecule Binding to Disordered Proteins. J Mol Biol. 2018;430:2288-2292 pubmed publisher
  9. Sormanni P, Camilloni C, Fariselli P, Vendruscolo M. The s2D method: simultaneous sequence-based prediction of the statistical populations of ordered and disordered regions in proteins. J Mol Biol. 2015;427:982-996 pubmed publisher
  10. Kukić P, Alvin Leung H, Bemporad F, Aprile F, Kumita J, De Simone A, et al. Structure and dynamics of the integrin LFA-1 I-domain in the inactive state underlie its inside-out/outside-in signaling and allosteric mechanisms. Structure. 2015;23:745-53 pubmed publisher
    ..These results suggest that the presence of three substates in the apo I-domain enables the precise regulation of the binding process that is essential for the physiological function of LFA-1. ..
  11. Fu B, Vendruscolo M. Structure and Dynamics of Intrinsically Disordered Proteins. Adv Exp Med Biol. 2015;870:35-48 pubmed publisher
  12. Ciryam P, Kundra R, Morimoto R, Dobson C, Vendruscolo M. Supersaturation is a major driving force for protein aggregation in neurodegenerative diseases. Trends Pharmacol Sci. 2015;36:72-7 pubmed publisher
    ..These observations suggest that effective therapeutic approaches designed to combat neurodegenerative diseases could be aimed at enhancing the ability of the cell to maintain the homeostasis of the metastable subproteome. ..
  13. Heller G, Sormanni P, Vendruscolo M. Targeting disordered proteins with small molecules using entropy. Trends Biochem Sci. 2015;40:491-6 pubmed publisher
  14. Bonomi M, Pellarin R, Vendruscolo M. Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy. Biophys J. 2018;114:1604-1613 pubmed publisher
  15. Joshi P, Vendruscolo M. Druggability of Intrinsically Disordered Proteins. Adv Exp Med Biol. 2015;870:383-400 pubmed publisher
    ..By analysing the results of recent studies, we describe the main structural features that may render IDPs druggable, and describe techniques that can be used for drug discovery programs focused on IDPs. ..
  16. Sormanni P, Aprile F, Vendruscolo M. Rational design of antibodies targeting specific epitopes within intrinsically disordered proteins. Proc Natl Acad Sci U S A. 2015;112:9902-7 pubmed publisher
    ..Taken together, these results indicate that the design strategy that we propose makes it possible to obtain antibodies targeting given epitopes in disordered proteins or protein regions. ..
  17. Borkar A, Bardaro M, Camilloni C, Aprile F, Varani G, Vendruscolo M. Structure of a low-population binding intermediate in protein-RNA recognition. Proc Natl Acad Sci U S A. 2016;113:7171-6 pubmed publisher
    ..These results identify the structure of an intermediate for RNA-protein binding and illustrate a general strategy to achieve this goal with high resolution. ..
  18. Ciryam P, Kundra R, Freer R, Morimoto R, Dobson C, Vendruscolo M. A transcriptional signature of Alzheimer's disease is associated with a metastable subproteome at risk for aggregation. Proc Natl Acad Sci U S A. 2016;113:4753-8 pubmed publisher
    ..These results suggest that the down-regulation of a metastable subproteome may help mitigate aberrant protein aggregation when protein homeostasis becomes compromised in Alzheimer's disease. ..
  19. Perni M, Challa P, Kirkegaard J, Limbocker R, Koopman M, Hardenberg M, et al. Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery. J Neurosci Methods. 2018;306:57-67 pubmed publisher
    ..We anticipate that this approach will further extend the scope and utility of C. elegans as a model organism. ..
  20. Bonomi M, Heller G, Camilloni C, Vendruscolo M. Principles of protein structural ensemble determination. Curr Opin Struct Biol. 2017;42:106-116 pubmed publisher
  21. Heller G, Aprile F, Vendruscolo M. Methods of probing the interactions between small molecules and disordered proteins. Cell Mol Life Sci. 2017;74:3225-3243 pubmed publisher
    ..In discussing these techniques, we also point out directions for future developments. ..
  22. Perni M, Aprile F, Casford S, Mannini B, Sormanni P, Dobson C, et al. Delivery of Native Proteins into C. elegans Using a Transduction Protocol Based on Lipid Vesicles. Sci Rep. 2017;7:15045 pubmed publisher
    ..elegans model of Parkinson's disease. As this transduction protocol is fast and inexpensive, we anticipate that it will be readily applicable to protein-based drug discovery studies that utilize C. elegans as a model organism. ..
  23. Heller G, Aprile F, Bonomi M, Camilloni C, De Simone A, Vendruscolo M. Sequence Specificity in the Entropy-Driven Binding of a Small Molecule and a Disordered Peptide. J Mol Biol. 2017;429:2772-2779 pubmed publisher
    ..These results suggest that the binding mechanism that we report may create novel opportunities to discover drugs that target disordered proteins in their monomeric states in a specific manner. ..
  24. Kundra R, Ciryam P, Morimoto R, Dobson C, Vendruscolo M. Protein homeostasis of a metastable subproteome associated with Alzheimer's disease. Proc Natl Acad Sci U S A. 2017;114:E5703-E5711 pubmed publisher
  25. Sormanni P, Amery L, Ekizoglou S, Vendruscolo M, Popovic B. Rapid and accurate in silico solubility screening of a monoclonal antibody library. Sci Rep. 2017;7:8200 pubmed publisher
  26. Chia S, Flagmeier P, Habchi J, Lattanzi V, Linse S, Dobson C, et al. Monomeric and fibrillar α-synuclein exert opposite effects on the catalytic cycle that promotes the proliferation of Aβ42 aggregates. Proc Natl Acad Sci U S A. 2017;114:8005-8010 pubmed publisher
    ..It is thus the specific balance between the concentrations of monomeric and fibrillar α-synuclein that determines the outcome of the Aβ42 aggregation reaction. ..