Imperial College London

DrAlfonsoDe Simone

Faculty of Natural SciencesDepartment of Life Sciences

Reader in Structural Biology
 
 
 
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Contact

 

+44 (0)20 7594 3052a.de-simon Website

 
 
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Location

 

603Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Summary

RESEARCH INTERESTS

Our research focuses on the physical principles underlying functional processes of bio-macromolecules by using integrated approaches of biomolecular NMR experiments and multiscale molecular simulations. Our interests range from understanding protein dynamics and interactions to membrane proteins, intrinsically disordered proteins and supramolecular host-guest interactions.

 Linkspublicationscitations, research highlights.


De Simone Lab (Dec 2017)De Simone's lab Dec 2017

Recent Research Highlights

Mechanism of membrane disruption and neuronal toxicity by Alpha-Synuclein oligomers.

Neurons

Toxic aSyn oligomers on the surface of primary cortical neurons

α-synuclein (αS) is an intrinsically disordered protein whose fibrillar aggregates are the major constituents of Lewy bodies in Parkinson’s disease. Our recent research has addressed the structural properties of toxic αS oligomers and the molecular basis by which these aggregates induce neuronal toxicity. More details on our Science paper.

Structural Mechanism of Synaptic Vesicle Assembly by Alpha-Synuclein

bridgeAlthough the specific function of αS is still unclear, a general consensus is forming that it has a key role in regulating the process of neurotransmitter release, which is associated with the mediation of synaptic vesicle interactions and assembly. We characterised the structural mechanism enabling αS to induce the clustering of synaptic vesicles. More details can be found on our Nature Communication article.

Selected Publications

Journal Articles

Fusco G, Chen SW, Williamson PTF, et al., 2017, Structural basis of membrane disruption and cellular toxicity by alpha-synuclein oligomers, Science, Vol:358, ISSN:0036-8075, Pages:1440-+

Fusco G, Pape T, Stephens AD, et al., 2016, Structural basis of synaptic vesicle assembly promoted by alpha-synuclein, Nature Communications, Vol:7, ISSN:2041-1723

Sanz-Hernandez M, Vostrikov VV, Veglia G, et al., 2016, Accurate Determination of Conformational Transitions in Oligomeric Membrane Proteins, Scientific Reports, Vol:6, ISSN:2045-2322

Fusco G, De Simone A, Gopinath T, et al., 2014, Direct observation of the three regions in alpha-synuclein that determine its membrane-bound behaviour, Nature Communications, Vol:5, ISSN:2041-1723

Krieger JM, Fusco G, Lewitzky M, et al., 2014, Conformational Recognition of an Intrinsically Disordered Protein, Biophysical Journal, Vol:106, ISSN:0006-3495, Pages:1771-1779

Biedermann F, Uzunova VD, Scherman OA, et al., 2012, Release of High-Energy Water as an Essential Driving Force for the High-Affinity Binding of Cucurbit[n]urils, Journal of the American Chemical Society, Vol:134, ISSN:0002-7863, Pages:15318-15323

De Simone A, Kitchen C, Kwan AH, et al., 2012, Intrinsic disorder modulates protein self-assembly and aggregation, Proceedings of the National Academy of Sciences of the United States of America, Vol:109, ISSN:0027-8424, Pages:6951-6956

More Publications