Translational Control in Plasmodium Sexual Development

  • Cui, Liwang (PI)

Project: Research project

Project Details


DESCRIPTION (provided by applicant): Malaria is a major health problem in many
countries of the world, causing about 2 million deaths annually. The increasing
spread of drug-resistant malaria parasites and insecticide-resistant vectors
has stimulated the research and development of new control strategies. One
strategy, focusing on the development of transmission-blocking vaccines, has
resulted in the characterization of a few sexual stagespecific antigen genes.
The identification of new targets for vaccine and drug development depends on
the expansion of our understanding of various molecular and cellular processes
of the parasite. Although malaria sexual stages are essential for the continued
transmission of the disease, the molecular mechanisms governing sexual
development of the parasite are largely unknown. To elucidate the molecular
mechanisms underlying sexual development in Plasmodium falciparum, the
interaction between an evolutionarily conserved RNA-binding protein (RBP) and
its target mRNA(s) will be characterized at the molecular level. In other
organisms, the best characterized members of this RBP family bind to 3'
untranslated regions of their target mRNAs and repress their translation. The
association of RBP members with germline cells in other organisms and the
differential expression of the P. falciparum RBP in sexual stages suggest a
related function for this protein in sexual differentiation and development of
the malaria parasite. The proposed studies will evaluate this hypothesis by
cloning the P. falciparuin RBP and characterizing its expression pattern,
subcellular location, and specific interaction with the target mRNA(s). The
target genes will be isolated and analyzed by employing the yeast three-hybrid
system and in vitro binding assays. The biological functions of the RBP and its
target gene(s) will be genetically studied using targeted gene disruption
techniques. The results of these studies will elucidate the importance of
translational control in sexual development and contribute to our understanding
of the fundamental molecular biology of the parasite, which may eventually lead
to the finding of novel targets for malaria control.
Effective start/end date3/15/012/28/07