BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Protein Misfolding Diseases. The Structural Determinants of Protei n Misfolded Oligomers Responsible for Toxicity and the Mechanism through w hich Toxicity is Mediated - Prof. Fabrizio Chiti\, Department of Experimen tal and Clinical Biomedical Sciences “Mario Serio”\, Section of Bioche mistry\, University of Florence\, Italy DTSTART:20181010T093000Z DTEND:20181010T103000Z UID:TALK112174@talks.cam.ac.uk CONTACT:Ryan Limbocker DESCRIPTION:The conversion of proteins from their native state to highly s tructured fibrillar deposits is associated with a number of neurodegenerat ive diseases. In these diseases a key role is played by the protein oligom er species that form as intermediate species or are released by mature fib rils. Such species are indeed highly toxic as they are able to interact wi th cellular targets and cause cell dysfunction. The structural factors res ponsible for protein oligomer toxicity and the mechanism of such toxicity will be described\, taking advantage of three pairs of toxic and nontoxic oligomers from three different protein systems\, namely the amyloid β ass ociated with Alzheimer’s disease\, α-synuclein associated with Parkinso n’s disease and the model protein HypF-N from E. coli. The use of a numb er of readouts of cell toxicity and of their time courses revealed the key events of the interaction between oligomers and biological membranes and the sequence of events in the toxicity cascade\, establishing that the des tabilization of the cell membrane with a Ca2+ influx is an early insult ca use by the oligomers. Given the importance of an altered calcium homeostas is in cells exposed to protein misfolded oligomers we have tried to identi fy the mechanism through which this homeostasis is compromised and the cal cium channels responsible for the abnormal calcium influx. LOCATION:Department of Chemistry\, Cambridge\, Unilever lecture theatre END:VEVENT END:VCALENDAR