Biomimetic models of extracellular vesicles: study of the role of GPI-anchored proteins in T. cruzi infection

• Grant number: 25/14394-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ana Claudia Trocoli Torrecilhas
• Grantee: Claudio dos Reis Ferreira
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 20/07870-4 - Mechanisms of trypanosomatid adaptation to hosts through the control of transcription, protein synthesis and secretion of extracellular vesicles, AP.TEM

Abstract

Chagas disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi that affects 7 million people globally. Currently, two antiparasitic drugs, benznidazole and nifurtimox, are available for treatment and are highly effective when combined with early detection of the infection. However, the high frequency of asymptomatic infections and subsequent progression to the chronic phase pose obstacles to both diagnosis and effective treatment of the disease. Infection of vertebrates by the parasite commonly occurs through vectors or ingestion of contaminated food and depends on the presence of highly glycosylated proteins on the surface of the parasite's plasma membrane. Among the glycoproteins important for host infection by the parasite are mucin-type glycoproteins and trans-sialidases, both classes of proteins associated with the membrane through GPI anchors. Mucins and trans-sialidases are important for adhesion and invasion of host cells and induce immunomodulatory effects important for infection. Trypomastigotes, the infectious forms of the parasite, release extracellular vesicles (EVs) by budding from the plasma membrane, transporting glycoproteins and consequently mediating T. cruzi infection. However, the precise role of these vesicles and the parasite's membrane glycoproteins has not yet been elucidated. In this context, this research project proposes to study the role of mucins and trans-sialidases in T. cruzi infection using synthetic vesicles. Based on the structural characterization of native EVs, we propose the reconstruction and biophysical characterization of the glycoproteins in different membrane models (liposomes), as well as the study of the immunological effects triggered by synthetic vesicles containing these proteins. The proposed approach will contribute to a greater understanding of the role of key membrane proteins in host-parasite interactions and may lead to the production of an immunizing particle with significant potential for the treatment and prophylaxis of Chagas disease.