Associate Professor Ph.D. Autonomous University of Madrid, Spain
	Phone: 901-678-2245 Fax: 901-678-4457 E-Mail: cestrano@memphis.edu
	University of Memphis Department of Biology Office:  409B Life Sciences Building Memphis, TN USA 38152

Research Interests:

Plasmodium falciparum is the causative agent of malaria which infects approximately 500 million people and kills approximately 2 million people per year. Children are most severely affected. Malaria is a significant public health problem that has been recently exacerbated by the rapid development of drug resistant parasites.

My research interest is focused on two aspects of malaria biology: (1) protein trafficking to the parasite food vacuole and its biogenesis. (2) Regulation of Plasmodium gene expression. The food vacuole is a metabolically active organelle. It is within the food vacuole that hemoglobin ingested by the parasite is degraded to peptides. The resulting free heme is detoxified upon its conversion to hemozoin. Hemoglobin digestion is a major target for drug chemotherapy due to its vital role in parasite survival.I utilize biochemical and genetic methods, specifically two hybrid and yeast complementation screens, to investigate the signals and mechanisms for targeting and delivery of proteins to the food vacuole. These approaches are viable because the P. falciparum food vacuole is functionally analogous to the yeast vacuole. We are searching the available P. falciparum database for the presence of plasmodial genes homologous to identified yeast genes involved in yeast vacuole biology.

Identified genes are being cloned, expressed and the structure-function relationship of the protein products of these genes determined.A second project in my laboratory is to identify P. falciparum promoter elements and determine the mechanism of transcriptional regulation. A few P. falciparum promoter sequences have been identified through comparisons with known eukaryotic promoter elements. The identified P. falciparum promoters are quite diverse in terms of their Cis-regulatory elements. TATA boxes have not been identified due to the high A-T content of intergenic regions (>90% A-T) which contain a high prevalence of homopolymeric (dA:dT) tracts.

The highly regulated transcriptional activity of P. falciparum genes is being studied during erythrocytic infection. In human red cells, P. falciparum genes are tightly regulated during differentiation into three morphologically distinct stages. The ring stage spans the first 24 hours post-invasion, the trophozoites are seen between 24-36 h and schizonts are found between 36-48 h.

Truncation and deletion analysis of a ring-specific hrp3 promoter luciferase reporter gene construct is being used to identify promoter regions required for stage specific transcriptional activity. Deletion of a 600 bp promoter segment virtually abolished promoter activity at ring stage with a concomitant increase in expression at the trophozoite stage. We are currently investigating the molecular mechanism underlying this switching of stage-specific expression of the truncated hrp3 promoter.