Apicomplexa are responsible for a number of important human diseases including malaria, toxoplasmosis, cryptosporidiosis and cyclosporidiosis. Management of these diseases rests heavily on chemotherapy but anti-parasitic drug treatment faces multiple challenges. These include poor overall potency, restriction to certain life-cycle stages, unwanted side effects, and rapidly emerging multiple drug resistance. A constant stream of new drugs and potential drug targets is required to stay abreast of the threat posed by these pathogens. One of the most promising sources of such parasite specific targets is the apicomplexan plastid or apicoplast. The apicoplast is unique to the parasite and its function is essential to parasite survival. This organelle is a holdover from a free-living photosynthetic past. The structure and biology of the apicoplast is remarkably complex as it is derived from the endosymbiotic marriage of two eukaryotes: a red alga and an auxotrophic protist. The goal of this application is to unravel the complexity of this biology in mechanistic detail and to identify future targets for intervention. Using Toxoplasma as a model organism we will conduct genetic, cell biological and biochemical approaches to characterize the function of two pathways that unfold in the outer compartments of the organelle and that we hypothesize are essential to the organelle and the parasites. We will complement this focused approach with a broader effort to define a comprehensive set of plastid proteins to continue to feed a pipeline of hypothesis-driven mechanistic experiments with strong candidate genes.

Public Health Relevance

Toxoplasma gondii is an important human pathogen that causes disease in the unborn fetus, young children and patients with a weakened immune system. We are a studying a unique cellular structure of the parasite that is related to the chloroplast of plants. A detailed understanding of the biology of this structure will lead us to new parasite specific interventions to treat and prevent disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Rogers, Martin J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Georgia
Public Health & Prev Medicine
Organized Research Units
United States
Zip Code
Fellows, Justin D; Cipriano, Michael J; Agrawal, Swati et al. (2017) A Plastid Protein That Evolved from Ubiquitin and Is Required for Apicoplast Protein Import in Toxoplasma gondii. MBio 8:
van Dooren, Giel G; Yeoh, Lee M; Striepen, Boris et al. (2016) The Import of Proteins into the Mitochondrion of Toxoplasma gondii. J Biol Chem 291:19335-50
Suvorova, Elena S; Francia, Maria; Striepen, Boris et al. (2015) A novel bipartite centrosome coordinates the apicomplexan cell cycle. PLoS Biol 13:e1002093
Sheiner, Lilach; Fellows, Justin D; Ovciarikova, Jana et al. (2015) Toxoplasma gondii Toc75 Functions in Import of Stromal but not Peripheral Apicoplast Proteins. Traffic 16:1254-69
Daher, Wassim; Morlon-Guyot, Juliette; Sheiner, Lilach et al. (2015) Lipid kinases are essential for apicoplast homeostasis in Toxoplasma gondii. Cell Microbiol 17:559-78
Lentini, Gaelle; Kong-Hap, Marie; El Hajj, Hiba et al. (2015) Identification and characterization of Toxoplasma?SIP, a conserved apicomplexan cytoskeleton protein involved in maintaining the shape, motility and virulence of the parasite. Cell Microbiol 17:62-78
Lévêque, Maude F; Berry, Laurence; Cipriano, Michael J et al. (2015) Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in Toxoplasma gondii. MBio 6:e01446-15
Williams, Melanie J; Alonso, Hernan; Enciso, Marta et al. (2015) Two Essential Light Chains Regulate the MyoA Lever Arm To Promote Toxoplasma Gliding Motility. MBio 6:e00845-15
Beckmann, Elena A; Köhler, Anna M; Meister, Cindy et al. (2015) Integration of the catalytic subunit activates deneddylase activity in vivo as final step in fungal COP9 signalosome assembly. Mol Microbiol 97:110-24
Ramakrishnan, Srinivasan; Docampo, Melissa D; MacRae, James I et al. (2015) The intracellular parasite Toxoplasma gondii depends on the synthesis of long-chain and very long-chain unsaturated fatty acids not supplied by the host cell. Mol Microbiol 97:64-76

Showing the most recent 10 out of 42 publications