CANCELLED Professor Alessio Ciulli (University of Dundee) presents his work on protein-protein interactions and protein degradation to discover novel therapeutics. Hosted by Dr Bill Grey.
Event details
Abstract
Our laboratory at the Centre for Targeted Protein Degradation (CeTPD) reveals molecular information on protein interactions and ubiquitination complexes and mechanisms to design novel molecular therapeutics and concept. Protein degrader, also known as PROTACs (PROteolysis-TArgeting Chimeras) and molecular glues, recruit a target protein to a ubiquitin E3 ligase for targeted protein degradation. Formation of a stable ternary complex between the degrader, the E3 ligase and the target is a critical step that leads to productive tagging of the target protein by ubiquitination, and subsequent proteasomal degradation. Our research has illuminated fundamental structural and biophysical insights into molecular recognition and mechanism of action of protein degraders, that have guided the design and optimization of novel small molecules for hard-to-target proteins, including Brd9, SMARCA2, KRAS and LRRK2. In my lecture, I will illustrate key lessons from these fundamental work and drug discovery campaigns. I will then outline recent studies involving creative design and mechanistic insights, that have ushered development of exciting new concepts, such as trivalent PROTACs, dynamics combinatorial PROTACs, and intramolecular bivalent glues.
About the speaker
Professor Alessio Ciulli
Alessio Ciulli studied chemistry in Florence, Italy, and obtained his PhD as a Gates Scholar from the University of Cambridge, UK, in 2006. After postdoctoral research as a College Research Fellow at Cambridge and a brief visit at Yale University in the USA, he returned to Cambridge to start his independent laboratory in 2010 upon the award of a BBSRC David Phillips Fellowship. In 2013, he was awarded an ERC Starting Grant and moved to the University of Dundee, UK, where he was promoted to full professor in 2016. He has received numerous prizes and awards for his discoveries, including the EFMC Prize for Young Medicinal Chemist in Academia (2015), the ICBS Young Chemical Biologist Award (2015), the RSC Capps Green Zomaya Award (2016), the RSC MedChemComm Emerging Investigator Lectureship (2016), and the Prous Institute - Overton and Meyer Award for New Technologies in Drug Discovery (2022). In 2023 he was elected Fellow of the Royal Society of Edinburgh (FRSE). He is the scientific founder of Amphista therapeutics, a targeted protein degradation company spin out of his laboratory, and the founder and director of the University of Dundee’s new Centre for Targeted Protein Degradation (CeTPD) which opened its laboratories in January 2023. The Ciulli research group designs and develops small molecules inducing targeted protein degradation and modulating protein-protein interactions. Their research takes a multidisciplinary approach including organic and medicinal chemistry and computational tools to design and developed high-quality molecules; structural biology and biophysics to study binary and ternary complexes in solution and reveal structural and dynamic interactions; and chemical biology, biochemistry, proteomics and cell biology to study the cellular impact of our small molecules into relevant cellular systems and disease models, Ciulli is passionate about translating fundamental research via collaboration partnerships with the biopharma industry and by creation of spin-out companies.