ProteoCure Webinar

Francesca Ester Morreale 

Thursday, February 22nd 2024, at 13.00 CET

Enabling targeted protein degradation in bacteria

Francesca Ester Morreale is a Group Leader at the Francis Crick Institute, her research group focuses on establishing targeted protein degradation technology in bacteria. Ester obtained her PhD in Pharmaceutical Sciences in 2014 from the University of Messina (Italy). She later joined Prof. Helen Walden’s research group at the MRC PPU (Dundee, UK) for a first postdoc, co-supervised by Prof. Alessio Ciulli. In 2017 she moved to Vienna (Austria), starting a second postdoc in Dr Tim Clausen’s group at the Research Institute of Molecular Pathology (IMP). In 2023 Ester joined the Francis Crick Institute as a Group Leader.

Webinar Summary: Targeted protein degradation technology offers unique opportunities for basic research and drug discovery. Yet application in bacteria has remained unexplored, due to the lack of a ubiquitin-proteasome system in prokaryotic cells. In our study, we investigated the possibility of translating the concept to bacteria, to fulfil the urgent need of novel antibiotic development approaches. Among bacteria-specific protein degradation systems, we focused on ClpCP, composed of an ATP-driven unfoldase (ClpC) selecting substrate proteins and translocating them into the protease compartment (ClpP). ClpCP is critical for protein quality control in Gram-positives and mycobacteria. We thus designed bifunctional small molecules, which we named bacterial proteolysis targeting chimeras (BacPROTACs), composed of a ClpC binding ligand connected to a substrate-recruiting moiety, and demonstrated that ClpCP can be reprogrammed towards selected proteins of interest.

BacPROTAC technology represents a versatile research tool and paves the way to novel antibiotic development strategies

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