Authors

A E Miele¹; D De Stefano¹; F Angelucci³; G Boumis²; F Fata³; I Silvestri³; D L Williams⁴;  ¹ Université Claude Bernard Lyon 1, France;  ² Sapienza University of Rome, Italy;  ³ University of L'Aquila, Italy;  ⁴ Rush University Medical Center, United States

Discussion

Eradication of helminth infections is one of the pillars of the WHO Roadmap2030 to attain global health goals. Worms have evolved to evade the host immune response, while travelling through and residing in the host body. It is therefore important, for both diagnostics and therapeutics, to know which are the molecular players in this survival game. In particular, for the human parasite Schistosoma mansoni, the present diagnostic methods are not able to detect the early stages of infection and MDA relies on only one drug.
Thereby the identification and characterization of key macromolecular targets is of utmost importance. The advances in genomics, proteomics and metabolomics have prompted this task to more rational and interdisciplinary strategies, where structural techniques, such as crystallography, SAXS, electron microscopy are pivotal. We are integrating structural biology with bioinformatics, molecular biology, biochemistry, biophysics and medicinal chemistry to select protein targets and to functionally and structurally characterise them.
>Our laboratories are focussing on 2 main subjects: (a) focussed structural genomics of the thiol-mediated detoxification metabolism; (b) structural characterization of the worm secretome. In the former case we have elucidated the entire pathway and selected 3 candidates to perform cycles of structure-based drug design; in the latter the aim is to understand what is at the interface between the worm and the host and to select which macromolecules might become good diagnostics and/or vaccine candidates. The information thus obtained is used to shed light into the challenging biological questions opened by a eukaryotic parasite that knows our immune system and its regulation better than we do.