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Communication Dans Un Congrès Année : 2021

Integrative structural biology in molecular parasitology: new strategies for old diseases

Résumé

Parasitic diseases are a major threat to human health, especially in countries in which access to sanitation and treatment is extremely limited. Eradication of helminth infections is one of the pillars of the recently launched WHO roadmap 2030 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 important for both diagnostics and therapeutics, to know the molecular players in this survival game. In particular, for the human parasite Schistosoma mansoni the methods of diagnosis are not able to detect the early stages of infection and WHO mass drug administration relies on only one drug. Therefore, the identification and characterization of key macromolecular targets for diagnostic and drug discovery is of utmost importance. Advances in genomics, proteomics and metabolomics have directed this task to more rational and interdisciplinary strategies, where structural techniques, such as macromolecular crystallography, SAXS and 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. In the last fifteen years we have deposited 41 structures in the PDB on two main subjects of research in our laboratories: (a) focussed structural genomics of the thiolmediated detoxification metabolism; (b) structural characterization of the worm secretome. In the former case we have elucidated the entire pathway and selected 2 candidates to perform cycles of structure-based drug design; in the latter the objective 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 currently used to shed light on the challenging biological questions opened by a vector-borne eukaryotic parasite that knows our immune system and its regulation better than we do.
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Dates et versions

hal-04004310 , version 1 (24-02-2023)

Identifiants

  • HAL Id : hal-04004310 , version 1

Citer

Adriana E. Miele, Angelucci Francesco, Boumis Giovanna, Silvestri Ilaria, Fata Francesca, et al.. Integrative structural biology in molecular parasitology: new strategies for old diseases. Protein Data Bank Symposium - 50th Year Celebration, ASBMB | AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, May 2021, online, United States. ⟨hal-04004310⟩
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