Identification and characterization of TRAF2 (TNF Receptor Associated Factor 2) interaction partners in Schistosoma mansoni

• Grant number: 24/11480-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Katia Cristina Pereira Oliveira Santos
• Grantee: Thainá Vinha Paiva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schistosoma mansoni parasite is the principal causative agent of schistosomiasis in tropical and subtropical regions, including Brazil. Several studies have demonstrated the importance of signaling pathways in the development and reproduction of schistosomes. Previous tests by our research group identified the human TNF-alpha receptor in S. mansoni and in other helminths, as well as demonstrated the importance of this cytokine in the development, metabolism and reproduction of the parasite by altering the gene expression profile, protein phosphorylation and alterations in the metabolism/oviposition. An essential class of adaptor proteins that interact with TNF-alpha receptors, the TRAFs (TNF receptor-associated factors), will activate and regulate various signaling pathways of the parasite, including apoptosis and cell proliferation. Seven TRAFs (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6 and TRAF7) are known in the literature in mammals, and our research group has identified two TRAFs in S. mansoni and the interaction of SmTRAF1 with the SmTNFR receptor has already been proven by the yeast double hybrid (Y2H) method.The main aim of this project is to identify and characterize the interaction partners of TRAF2 by screening a cDNA library of adult worms using the yeast double hybrid technique. The ZF-RING and Math domains of SmTRAF2 will be used once possible downstream and upstream interaction targets have been identified. Direct interaction assays will be carried out to confirm the interaction between the SmTRAF2 domains and the identified candidates and with SmTNFR. From the results obtained, we will gain in-depth knowledge of the biology of the parasite and the molecular processes involved in its development and, thus, devise new strategies for combating and controlling schistosomiasis in the future.