Giuseppe Melacini is the Director of the Chemical Biology Graduate Program at McMaster University. He is a Professor in the Department of Chemistry and Chemical Biology and a joint member of the Department of Biochemistry and Biomedical Sciences.
Dr. Giuseppe Melacini received his undergraduate degree in Chemistry (1992) and his PhD in Biophysical Chemistry (1996) from the University of Milan with external research at the University of California, San Diego (UCSD). During his graduate studies, he worked in the area of peptidomimetics under Dr Murray Goodman at UCSD. Then he moved to the Netherlands for his post-doctoral studies in the laboratories of Robert Kaptein and Rolf Boelens at Utrecht University. There he focused on the study of protein hydration through Nuclear Magnetic Resonance spectroscopy. After returning to UCSD as Lecturer and Assistant Project Scientist, he joined the Departments of Chemistry and Biochemistry at McMaster in 2003.
In 2018-2019 Giuseppe served as Associate Chair of graduate studies in Chemistry, and since July 2019 as Director of the Chemical Biology graduate program.
Giuseppe is the recipient of the Biological and Medicinal Chemistry Lectureship Award by the Canadian Society of Chemistry (2020), the Excellence in Graduate Student Supervision Award (2019), Natural Sciences and Engineering Research Council – Discovery Accelerator Supplement Award (2014), McMaster Student Union – Teaching award (2012), Canadian Institutes of Health Research – Maud Menten Finalist Prize (2007), Heart & Stroke Foundation of Canada – New Investigator Award (2006) and Maureen Andrew Award (2006), Alzheimer Society of Canada – Young Investigator Award (2005), Premier’s Research Excellence Award (2005).
Giuseppe has served on multiple grant review panels in Canada, and has reviewed US, European and Israeli grant applications. He has been an executive member of the Biophysical Society of Canada for which he chaired the award committee (2014-2019). He has also co-organized and co-chaired several conferences. He has consulted for biopharmaceutical and biotech companies.
He is the author of over 110 peer-reviewed publications and is a member of the editorial boards of the Journal of Biological Chemistry and Nature Scientific Reports. He has served as associate editor for the Journal of Alzheimer’s Disease and as invited expert editor for the Proceedings National Academy Science USA (PNAS).
Giuseppe is very proud to have something in common with Jeff Bezos and Bill Gates – he does the dishes every night.
Atomic Resolution Map of the Soluble Amyloid Beta Assembly Toxic Surfaces
Soluble amyloid beta assemblies (Aβn) are neurotoxic and play a central role in the early phases of the pathogenesis cascade leading to Alzheimer’s disease. However, the current knowledge about the molecular determinants of Aβn toxicity is at best scant. Here, we comparatively analyze Aβn prepared in the absence or presence of a catechin library that modulates cellular toxicity. By combining solution NMR with dynamic light scattering, fluorescence spectroscopy, electron microscopy, wide-angle X-ray diffraction and cell viability assays, we identify a cluster of unique molecular signatures that distinguish toxic vs. nontoxic Aβ assemblies. These include the exposure of a hydrophobic surface spanning residues 17-28 and the concurrent shielding of a highly charged N-terminus. We show that the combination of these two dichotomous structural transitions promotes the colocalization and insertion of β-sheet rich Aβn into the membrane, compromising membrane integrity. These previously elusive toxic surfaces mapped here provide an unprecedented foundation to establish structure-toxicity relationships of Aβ assemblies.
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