19:00: Arrival of attendees and networking
19:30: Talks from organising societies
19:40: Talk from Prof Alessio Ciulli
Professor Dr Alessio Ciulli, FRSC
University of Dundee, Dundee, UK
Alessio Ciulli studied chemistry in Florence, Italy, and obtained his PhD from the University of Cambridge, UK, in 2006. After postdoctoral research in Cambridge and at Yale University, USA, he returned to Cambridge in 2009 to start his independent laboratory. In 2013, he moved to the University of Dundee, UK, where he was promoted to full professor in 2016. He received several awards, including a BBSRC David Phillips Fellowship, an ERC Starting Grant, the EFMC Young Medicinal Chemist award, the ICBS Young Chemical Biologist Award, the MedChemComm Emerging Investigator Lectureship and the RSC Capps Green Zomaya Award, and is a Fellow of the Royal Society of Chemistry. He is the scientific founder of Amphista therapeutics, a targeted protein degradation company spin out of his laboratory, and the founder of Dundee’s new Centre for Targeted Protein Degradation which he directs and is to open in Spring 2022.
Alessio Ciulli is one of the pioneers of using molecular information on protein-protein interactions and protein degradation to discover novel therapeutics. In cancer, one such drug target is the E3 ubiquitin ligase VHL, which can be hijacked by PROTACs (PROteolysis-Targeting Chimeras) to guide proteins to the proteasome to be destroyed. Ciulli solved the structure of VHL bound to fragments of its natural substrate and analysed it to design and synthesize novel small molecule inhibitors of VHL. He tethered one of these to another small molecule inhibitor of his design targeting BRD4, a protein frequently deregulated in leukemia. The resulting PROTAC bridges BRD4 with VHL and removes BRD4 from leukemic cells. Solving the structure of the ternary bridging complex, he unravelled how the PROTAC induces selective degradation. With the same approach, he has developed further small molecules for hard to target proteins and shown how to improve existing PROTACs.