Francesca Mosca

Doctoral candidate at Centre National de la Recherche Scientifique (CNRS)

About me

Coming from a small town in Umbria, Italy, I obtained my Master’s degree in Chemical Sciences, Organic Chemistry curriculum, from the University of Perugia. In 2021 I got my Bachelor’s degree in Chemistry from the same university, after completing 3 months of thesis work in a green organic chemistry laboratory.

During the first three years of my studies, I studied all different types of chemistry, including organic, inorganic, analytical, physical chemistry and biochemistry. In the last two years, I developed a strong interest in biological, medicinal chemistry and drug discovery. During this time I had the opportunity to develop many skills, including organic synthesis, characterisation of compounds by spectroscopic methods and the use of some software for drug discovery. Indeed, my Master’s thesis focused on the synthesis of PROTACs for GPX4 protein and their characterization by NMR, while the computational part involved the in silico prediction of physicochemical properties and metabolism and the generation of a solubility model for PROTACs.

I expect to learn lots of new things from this project, to grow as a scientist and as a human, and to get in touch with a stimulating and welcoming environment. I am honoured to be part of this project, which has the ultimate goal of solving a problem that affects all humans. I am really grateful for the opportunity I was given and I hope to make a constructive contribution by doing my best.

About my project
DC06: Elucidation of Lpp L,D-transpeptidases structure to enable in silico design of inhibitors and design of an in vitro screening assay for new inhibitors

The goal of this project is to resolve the function of the LdtA,B,C transpeptidases that link Braun’s Lpp to the bacterial cell wall. In enterobacteria, thousands of Braun’s OM Lpps are bound to the peptidoglycan layer. Although Lpp is not essential, cells lacking Lpp show enhanced membrane blebbing and sensitivity to antibiotics because of increased OM permeability. Thus, targeting Lpp attachment to the PG should lead to bacterial clearance in patients. The L,D-TPases LtdA, B and C are the presently known candidates for the crosslinking of Lpp to peptidoglycan. NMR and/or X-ray crystallography will be used to study the structure of the different Ldts as well as their interaction with the peptidoglycan and the LPP. In parallel, docking studies will be performed with substrates and inhibitors and different biophysical methods will be used to characterize the interaction between Ldt and inhibitors synthesised by other groups in the BREAKthrough consortium. The characterisation of the interaction between the identified ligands and their targets will help to design improved molecules.