: Plasmodium falciparum causes the most virulent of human malarias. The blood stage parasites comprise of morphologically distinct ring, trophozoite and schizont stages with distinct patterns of gene expression. For instance, the surface adhesion var genes (that have attracted particular interest for their role in pathogenesis) show promiscuous transcription in rings but restricted expression in trophozoites. However whether gene expression is regulated at the level of transcription, message stability and mediated by sequence elements in the UTRs is poorly understood for both VARs and other plasmodial genes. The long-term goals of this project are to understand mechanisms of stage specific gene regulation in Plasmodium falciparum. The study will contribute to our basic understanding of lower eukaryotic gene expression and the regulation of genes such as vars that play an important role in disease pathology. Molecular, genetic tools including transfection to express promoter fusions, combined with biochemical subcellular fractionation assays, will be used to identify elements of gene regulation. Unique mechanisms in var regulation may provide targets against cerebral malaria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI054529-02
Application #
6722905
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rogers, Martin J
Project Start
2003-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2006-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$74,250
Indirect Cost
Name
Northwestern University at Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Lopez-Estrano, Carlos; Gopalakrishnan, Anusha M; Semblat, Jean-Philippe et al. (2007) An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum. Biochim Biophys Acta 1769:506-13
Lopez-Estrano, Carlos; Semblat, Jean-Philippe; Gopalakrishnan, Anusha M et al. (2007) Plasmodium falciparum: hrp3 promoter region is associated with stage-specificity and episomal recombination. Exp Parasitol 116:327-33
Catron, Drew M; Lange, Yvonne; Borensztajn, Jayme et al. (2004) Salmonella enterica serovar Typhimurium requires nonsterol precursors of the cholesterol biosynthetic pathway for intracellular proliferation. Infect Immun 72:1036-42