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Structural Characterization of Schistosome Vault Particles


EMSL Project ID
51014

Abstract

Schistosomiasis is a disease caused by parasitic flatworm schistosome, and affects about 252 million
people each year. In tropical countries, schistosomiasis is second only to malaria among parasitic diseases with
the greatest economic impact. Two out of five people world-wide, live in areas where the disease is common.
Praziquantel (PZQ) is the only drug for schistosomiasis since 1970s, however, severe drug resistance has been
reported in Africa in recent years, with an extremely low cure rate of 18% in Senegal, urging research for the
mechanism of PZQ resistance in schistosomiasis.
Vault has been associated with PZQ resistance in schistosome. It is the largest cytosolic ribonucleoprotein
in eukaryotes, highly conserved among sponge, flatworms, and vertebrates. Despite being discovered since 1986,
the molecular function of vault remains elusive. In collaboration with Bo Wang lab at Stanford University, we
discovered that knock-down of major vault protein (MVP) in Schistosoma mansoni leads to an increased sensitivity
to PZQ in both juvenile and adult worms. Here we aim to determine the molecular structure of vault particle in
schistosome and uncover its role in PZQ resistance. Our effort will lead to new strategies to tackle the
challenges of schistosomiasis.

Project Details

Start Date
2019-09-01
End Date
2020-02-14
Status
Closed

Team

Principal Investigator

Minglei Zhao
Institution
University of Chicago

Team Members

Theo Humphreys
Institution
Oregon Health & Science University

Yuan Xie
Institution
University of Chicago