Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V47
Höfundar / Authors: Delia Bogenstätter (1), Gaelle Lentini (2)
Starfsvettvangur / Affiliations: 1. Institute of Cell Biology, University of Bern, Switzerland; 2. Institute of Cell Biology, University of Bern, Switzerland
Kynnir / Presenter: Delia Bogenstätter
Trypanosoma cruzi, the protozoan parasite responsible for Chagas disease, is a major but neglected cause of parasitic illness in the Western Hemisphere. Its life cycle includes a replicative intracellular amastigote stage in mammalian host cells, followed by differentiation into trypomastigotes. These motile and infective forms are released upon host cell lysis in a process known as egress, a critical step for parasite dissemination and transmission. Despite its importance, the molecular mechanisms underlying egress remain unknown. We hypothesize that host cell lysis is mediated by regulated secretion of parasite virulence factors, particularly proteases, a view supported by suggestive observations. Here we use the first knockdown system developed for T. cruzi as a tool to study proteins involved in egress. This system induces degradation of specific target mRNAs and thereby reduces protein levels, enabling functional analysis of essential genes. We successfully establish this system in the laboratory by targeting Aurora kinase 1, a conserved kinase involved in mitosis. We are now applying this approach to functionally characterize a subset of T. cruzi proteases identified by bioinformatics and comparative proteomics comparing the proteomes of freshly egressed parasites with intracellular parasites shortly before egress. Defining the roles of these proteases may uncover virulence factors that mediate egress and highlight novel therapeutic targets for Chagas disease.