Giuseppe Melacini

Giuseppe Melacini
McMaster University (ON)

We are primarily interested in two main fields of research: the allosteric conformational switches that control signaling pathways and the early steps of amyloid fibril formation. Allosteric conformational switches in signalling pathways: We are currently mapping the intra-molecular signaling pathways and the dynamic changes that propagate the signal carried by second messengers. So far our work has focused mainly on the exchange protein directly activated by cAMP (EPAC) and on the prototypical receptor for cAMP, i.e. protein kinase A (PKA). Early steps of amyloid fibril formation: We are currently investigating the mechanism of nucleation and of inhibition of amyloid fibrils. So far our work in this field has mainly focused on the Ab system and on endogenous proteins that inhibit its pathogenic oligomerization (e.g. Human Serum Albumin or HSA). These projects have several medical implications ranging from cardiac tumors to Alzheimer’s disease and type II diabetes. These projects also have in common a strong component based on high-field multidimensional multinuclear NMR. When required to address questions relevant to the projects above, we also adapt and customize existing NMR tools and pulse sequences.