[R21] Role of Cryptosporidium effectors in host actin manipulation
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2028-04-30
Importo max: 226.768 EUR
Paese: US
Descrizione
Project Abstract
The protozoan parasite Cryptosporidium is a leading cause of diarrheal disease (cryptosporidiosis) and death in
young children and immunocompromised individuals. Currently, there are no vaccines or effective drugs to
prevent or treat cryptosporidiosis. Our understanding of the interactions of Cryptosporidium with its host cell is
very limited. Cryptosporidium has a unique mode of invasion that differs from other related apicomplexan
parasites. The parasite creates an ‘intracellular but extracytoplasmic’ niche where it sits on top of the intestinal
epithelial cell, engulfed by the host cell membrane, and is separated from the host cell cytoplasm. A key feature
of Cryptosporidium invasion is the rapid polymerization of host actin and cell remodeling, which leads to the
formation of the trophozoite with an ‘actin pedestal’ underneath at the host-parasite interface. Although
Cryptosporidium releases hundreds of secretory effector proteins from four organelles—rhoptries, micronemes,
dense granules, and the newly discovered ‘small granules’—the role of these proteins in host-parasite
interactions remains largely unknown. Notably, the parasite effectors that manipulate the host machinery to
promote actin polymerization during invasion are not known. To address this knowledge gap, we have identified
Cryptosporidium secretory proteins that are potentially involved in manipulating host actin polymerization
machinery during invasion for the parasite to establish its unique niche. The goal of this exploratory proposal is
to utilize a combination of molecular genetics and cell biology approaches, and animal infection experiments to
investigate the role of the top identified candidates and their interacting host proteins in promoting actin
polymerization. The results of this study will improve our understanding of Cryptosporidium biology and host-
parasite interactions. The new knowledge gained from this work will support future development of vaccines and
effective therapies against cryptosporidiosis.
Istituzione: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
PI: Sumiti Vinayak Alam
Progetto: 1R21AI200215-01
Settori: National Institute of Allergy and Infectious Diseases
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