We are interested in the cell and molecular biology of protozoan parasites. Most of our work is focused on members of the phylum Apicomplexa. Organisms in this group cause a number of important diseases including malaria, severe opportunistic infections associated with AIDS, and fetal and early childhood diseases. We use a broad array of modern genomic, genetic, cell biological and biochemical approaches to understand fundamental parasite biology and use this knowledge to identify and develop targets for disease intervention. Currently we are focusing on the following specific areas:

The function and cell biology of the parasite chloroplast

Apicomplexan parasites harbor a remnant chloroplast (the apicoplast) that they obtained through secondary endosymbiosis. This organelle is essential for parasite growth and as human cells lack chloroplasts offers a unique opportunity for anti-parasitic drug development.
Using Toxoplasma gondii as a robust genetic model we are characterizing the specific metabolic functions of the organelle to pinpoint which pathway(s) would be most suitable as a drug target (see Mazumdar & Striepen, 2007 for a review of some of this work). The apicoplast also provides a tractable model to study the cell biology of endosymbiosis. What is the cellular machinery that builds, maintains and replicates and organelle that formed due to the merger of three previously independent organisms (one prokaryotes and two eukaryotes). Our current work uses a mix of genomics and genetics to mechanistically dissect apicoplast biogenesis, protein import and division. These two review articles (Vaishnava & Striepen, 2006, Striepen et al., 2007) summarize our most recent work and ideas on apicoplast and parasite cell biology.

Novel targets for the treatment of cryptosporidiosis

Cryptosporidium is an important human pathogen causing severe disease in AIDS patients and young children. Neither vaccines nor fully effective drugs are available for this disease. We are studying the nucleotide metabolism of Cryptosporidium parvum in an effort to develop effective therapy. We have discovered that the parasite depends entirely on salvage of purines and pyrimidines from its host cell and that several key enzymes were obtained via horizontal gene transfer from a bacterial source (Striepen et al., 2002; Striepen et al., 2004). Current work is focused on the further development of lead compounds obtained through a completed high throughput screen (Umejiego et al., 2008). Taking a broader biological perspective we are also interested to learn what the selective advantages might been that have fixed these bacterial genes in the parasite's eukaryotic genome.

Forward genetic analysis in Toxoplasma gondii

Forward genetic analysis by mutant isolation and complementation is a powerful approach to dissect pathogen biology. Over the last years we have developed a number of strategies and reagents to push this technology forward. We have isolated temperature sensitive mutants using a fluorescent parasite line in a high throughput replica assay. To identify the genes affected in these mutants we have developed an expression cloning system for phenotypic complementation (Striepen et al 2002; White et al., 2005; Gubbels et al., 2008) . In addition we have also used this system for expression cloning using antibodies (Radke et al., 2004) and GFP localization (Gubbels et al., 2004) as screens.

Please refer to our publications for further detail on our research.

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