CIRCADIAN POLYPHARMACOLOGY IN AD: DISCOVERY OF MULTITARGET-DIRECTED LIGANDS
Home institution: Alma Mater Studiorum University of Bologna – Italy (24 months)
Host institution: Faculdade de Farmácia da Universidade de Lisbon – Portugal (10 months)
PhD Enrolment #1: Alma Mater Studiorum University of Bologna – Italy
PhD Enrolment #2: Universidade de Lisbon – Portugal
Supervisor #1: Elisa Uliassi
Supervisor #2: Rita Guedes
Intersectoral Secondment: Circadian Therapeutics – UK
Objectives:
The BOMedCHem lab (https://site.unibo.it/medchembolab-bolognesi/en) at the Department of Pharmacy and Biotechnology, University of Bologna, Italy, is looking to appoint a Marie Curie Research Fellow within a fixed term project entitled “Circadian polypharmacology in AD: discovery of multitarget-directed ligands”, funded by the Horizon Europe project TClock4AD. The doctoral candidate will work for two years in Italy (University of Bologna) and for 10 months in Portugal (Lisbon University) and will be involved in a 2-month secondment to a UK-based company (Circadian Therapeutics).
The main objective of DC2 will be to exploit ligand-based and structure-based design approaches to develop novel inhibitors with a balanced profile against two selected kinase targets regulating circadian clock (CC). A new combination of targets critically involved in CC disfunction will be also identified from bioinformatic studies in collaboration with DC4. Initial hits against these new pair of targets will be synthesized. Compounds will be purified, characterized, and tested against the two sets of target combinations through interaction with DC5 (WP1). Cellular proof of concept will be performed, together with BBB and in vivo studies in collaboration with DC10 and 11 in WP3.
Expected outcomes:
The fellow is expected to generate breakthrough ideas in the assigned area of research, as well as to carry out research in line with the project plan. The fellow is also expected to contribute to dissemination and communication activities, besides actively collaborating within the TClock4AD network. This doctoral candidate will work closely with consortium partners at Lisbon University (PT) and Circadian Therapeutics (UK).
