DC 15: Sveva Pidello
Sveva Pidello (Italy) studied Pharmaceutical Chemistry and Technology at the University of Eastern Piedmont in Novara, Italy. During her studies, she fulfilled all pharmacist training requirements, including participation in the Erasmus Traineeship program, where she worked as a pharmacist intern in Dublin, Ireland. She completed her degree with a thesis in medicinal chemistry focused on the synthesis of dual inhibitors targeting Store-Operated Calcium Entry (SOCE) and Dihydroorotate Dehydrogenase (DHODH) for the treatment of autoimmune diseases.
After graduation, Sveva joined the University of Siena, where she carried out a one-and-a-half-year research fellowship dedicated to the synthesis of peptides as anticancer agents. Her work specifically targeted RAD52, a novel therapeutic target for the treatment of pancreatic cancer.
Planned secondments: 2 months at Université Paris-Cite (INEM) for the cellular testing of PROTAC degraders; 1 month at Cell Signalling Technology for proteomic analysis of S6K1/S6K2 degradation, 3 months at BiosolveIT for structure-based drug design
Université Paris Cité/INEM
2 monthsParis, France
Cell Signaling Technology
1 monthBoston, United States
BioSolveIT
3 monthsSankt Augustin, Germany
My research project
The deconvolution of the individual roles of the mTORC1 downstream kinases S6K1 (RPS6KB1) and S6K2 (RPS6KB2) has mostly relied on genetic tools, and only in the case of S6K1, pharmacological inhibition. Proteolysis Targeting Chimera (PROTACs) are a new modality enabling the degradation of a target protein with high specificity and spatiotemporal resolution by hijacking the ubiquitin- proteasome system. So far, PROTACs have neither been developed for S6K1 nor for S6K2. DC15 will generate selective PROTACs for each kinase. In parallel to determining binding affinities, chimeric degraders will be characterized in cellular assays for their degradation potency (DC50) and maximal level of degradation (Dmax). Ternary complex formation and degradation kinetics will subsequently be determined for key compounds in commercial bioluminescence resonance energy transfer (BRET)-based assays. While S6K1-selective PROTACs will build on selective non-covalent S6K1 inhibitors concomitantly identified in our ongoing S6K2 program, S6K2 PROTACs will be based on new reversible-covalent S6K2 inhibitors to grant isoform-selectivity and a substoichiometric protein turnover.
PhD enrolment : 
DC 14: Lucilla Paretti