Mariana L. Matrajt

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Office 802-656-3671
    Lab 802-656-3672
306 Stafford
Microbial Pathogenesis

Dr. Matrajt received her Ph.D. from the University of Buenos Aires, Argentina, where her dissertation research was awarded first prize by the Argentinean National Academy of Medicine for the best work in infectious disease diagnostics. Her postdoctoral training was carried out in the laboratory of Dr. David Roos at the University of Pennsylvania. Dr. Matrajt joined the faculty of MMG in 2004.

Research Interests

Genetics
Gene Expression & Regulation
Microbial Pathogenesis

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.




Selected Publications

Matrajt, M., Angel, S.O., Pszenny, V., Guarnera, E., Roos, D.S. and Garberi, J.C. Arrays of repetitive DNA elements in the largest chromosomes of Toxoplasma gondii. Genome. 1999 Apr;42(2):265-269.

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.

Matrajt, M., Nishi M., Fraunholz M., Peter O., and Roos D.S. Amino-terminal control of transgenic protein expression levels in Toxoplasma gondii. Mol Biochem Parasitol. 2002 Apr 9;120(2):285-289.

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.

Echeverria PC, Matrajt M, Harb OS, Zappia MP, Costas MA, Roos DS, Dubremetz JF, Angel SO. Toxoplasma gondii Hsp90 is a potential drug target whose expression and subcellular localization are developmentally regulated. J Mol Biol. 2005. 350(4):723-34.

All Matrajt publications