Membrane microdomains enriched in (glyco) (sphingo) lipds and sterols: organization, function and cell signaling

Abstract

In the past 10 years our laboratory did isolate and characterize various glycolipid antigens from Leishmania, Trypanosoma cruzi and pathogenic fungi. Glycolipid antigens are mainly located at the plasma membrane of these microorganisms, and recent results have shown the involvement of these molecules in processes of cell adhesion, recognition, and differentiation. The major objective of this project is to study in details the organization of lipids and glycolipids in microdomains at the plasma membrane, denominated membrane rafts, and their role in processes of adhesion, invasion, and survival of fungi and parasites in the mammalian host. Also, molecules from the host cells presumably involved in the interaction with these pathogens will be characterized, and the activated signal pathways will be analyzed in order to better understand the pathogen-host interaction. The specific objectives of this project will be focused to determine and characterize: 1) components of the microdomains enriched in (glyco) (sphingo) lipids in trypanosomatids and pathogenic fungi; 2) interaction of fungi and trypanosomatids, as well as its purified glycoconjugates, with mammal cells; 3) structure and function of specific antigens of parasites and fungi, aiming to identify new target molecules for action of more specific drugs; 4) in and in vivo effects of inhibitors involved in the biosynthesis of lipids, in the growth and infectivity of parasites and fungi; 5) the functional and organizational dynamics of the microdomains in the pathogenesis of these microorganisms; 6) reorganization of membrane rafts and cytoskeleton during phase transition in dimorphic pathogenic fungi; 7) processes of cellular signaling in the interaction of parasite-cell host and fungi-host cell; and 8) (glyco) lipidomic analysis of fungi and parasites aiming to detect possible virulence markers. (AU)