Two waterborne apicomplexan protozoa, Toxoplasma gondii and Cryptosporidium parvum, are potential biological weapons. T. gondii, a ubiquitous parasite of mammals and birds, has long been recognized as an important pathogen of both immune competent and immunocompromised hosts. T.gondii infection during pregnancy can result in congenital toxoplasmosis with associated encephalitis and chorioretinitis. In addition to its effects on children, adults can become infected with T. gondii through water supplies or food. The major syndrome caused by C. parvum is diarrhea, which can last for several weeks and can cause dehydration and death. Like T. gondii, the oocysts of this organism are also environmentally resistant and water-borne outbreaks have been described.

This center will develop an integrated approach to identify and validate new therapeutic drug targets based upon

  • the unique cytoskeletal scaffold that is a defining feature of all Apicomplexa.

  • membrane-associated proteins.

The apicomplexan cytoskeletal scaffold is a primary determinant of cell shape, and tethers functional protein assemblies in the cytosol and overlying membranes. Membrane proteins are positioned at the contact interface of parasites and their hosts and are involved in a diverse range of cellular functions including cell signaling/communication, nutrient and ion transport. We will use proteomics approaches to identify the proteins mediating inter- and intramolecular associations within the cytoskeletal complex as well as the overlying membranes. These macromolecular assemblies and membrane protein complexes, given their importance for cell function, will provide a rich source of novel targets for chemotherapy.

Recently reported infectious outbreaks: