Dr. Mariana L. Matrajt
The research in my lab focuses on the human pathogen Toxoplasma gondii. one of the most widely distributed protozoan parasites infecting approximately one-third of the world’s population (including ~1/3 of the US population). This parasite can infect any nucleated animal cell but is usually controlled by the cellular immune response, leaving a latent infection. In recent years, T. gondii has achieved notoriety as a cause of life-threatening opportunistic disease in immunocompromised individuals.
Asexual replication of T. gondii in humans and intermediate hosts is characterized by two forms: rapidly growing ‘tachyzoites’ and latent ‘bradyzoite’ tissue cysts both of which are essential for disease propagation and causation. Tachyzoites are responsible for acute illness and congenital neurological birth defects, while the more slowly dividing bradyzoite can remain latent within tissues life-long, presenting a continual threat to immunocompromised patients. The interconversion process between tachyzoites and bradyzoites is central to the parasite’s survival and pathogenicity, yet it remains poorly understood at the genetic and molecular level. Furthermore, there is no effective treatment for chronic toxoplasmosis due to the lack of drugs that eliminate tissue cysts. Therefore research in this area is likely to identify novel targets for both vaccine and drug development.
The long-term objective of our research is to elucidate the genetic basis and mechanisms underlying interconversion between tachyzoites and bradyzoites. We want to understand how T. gondii carries out the differentiation process and what molecular mechanisms are used by the parasite to sense environmental signals such as the ones that trigger bradyzoite formation. A wide variety of molecular tools are now available for the genetic manipulation of T. gondii parasites, tachyzoites are readily cultured in the laboratory, it is possible to induce bradyzoite differentiation in vitro and several stage specific markers are available to follow this process. In an effort to identify genes that are essential for cyst formation we have developed a genetic screen to identify regulatory genes that control parasite differentiation and have isolated mutants that fail to convert to bradyzoites under differentiation conditions (Matrajt et al, 2002). Our reseach is directed towards identifying the disrupted genes in these mutants and studying their function. We are scaling-up this genetic screen to isolate additional differentiation mutants with the goal of dissecting the genetic pathway that leads to bradyzoite formation and combining a genetic and genomic approach to identify genes that play a central role in T. gondii development.
Lescault PJ, Thompson AB, Patil V, Lirussi D, Burton A, Margarit J, Bond J, Matrajt M. Genomic data reveal Toxoplasma gondii differentiation mutants are also impaired with respect to switching into a novel extracellular tachyzoite state. PLoS One. 2010 Dec 30;5(12):e14463.
Matrajt M. Non-coding RNA in apicomplexan parasites. Mol Biochem Parasitol. 2010 Nov;174(1):1-7
Echeverria PC, Figueras MJ, Vogler M, Kriehuber T, de Miguel N, Deng B, Dalmasso MC, Matthews DE, Matrajt M, Haslbeck M, Buchner J, Angel SO. The Hsp90 co-chaperone p23 of Toxoplasma gondii: Identification, functional analysis and dynamic interactome determination. Mol Biochem Parasitol. 2010 Aug;172(2):129-40.
de Miguel N, Lebrun M, Heaslip A, Hu K, Beckers CJ, Matrajt M, Dubremetz JF, Angel SO. Toxoplasma gondii Hsp20 is a stripe-arranged chaperone-like protein associated with the outer leaflet of the inner membrane complex. Biol Cell. 2008 Aug;100(8):479-89.
Matrajt M., Platt C., Sagar A.D., Moulton L.C. and Roos D.S. Transcript initiation, polyadenylation, and functional promoter mapping in the dihydrofolate reductase-thymidylate synthase gene of Toxoplasma gondii. Molecular and Biochemical Parasitology, 2004. 137(2):229-38.
Matrajt M., Donald R.G.K, Singh U., and Roos D.S. Identification and Characterization of Differentiation Mutants in the Protozoan Parasite Toxoplasma gondii. Mol Microbiol. 2002 May;44(3):735-747.