Elisabetta Ullu

Professor, Internal Medicine/Section of Infectious Diseases, and Cell Biology
Ullu lab website Phone: (203) 785-3563 Fax: (203) 785-3864 e-mail: elisabetta.ullu@yale.edu		Section of Infectious Diseases Department of Internal Medicine Yale University School of Medicine 333 Cedar Street P.O. Box 208022 New Haven, CT 06520-8022   USA <Courier Address> 295 Congress Avenue, BCMM 136D New Haven, CT 06519-1418

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Regulation of gene expression in Trypanosoma brucei, the cause of African sleeping sickness.

African trypanosomes are flagellate protozoa of the family Trypanosomatidae which include a large number of diverse organisms some of which are parasites of great medical and economical importance. In the past, the interest in studying these cells stemmed primarily from their parasitic life-styles. However, more recently these organisms have caught the attention of the scientific community at large because of their unorthodox and unique mechanisms of gene expression like trans-splicing, polycistronic and polygenic transcription units, and RNA editing. Because trypanosomes are ancient eukaroytic organisms, which separated very early from the main branch of the eukaryotic lineage, their peculiar mechanisms of gene expression might reflect ancient eukaryotic functions which have been preserved to present times. By studying the process of gene expression in trypanosomes, not only do we learn about the evolution and functioning of the modern eukaryotic cell, but we also hope to identify parasite specific functions which might be exploited against the parasite themselves.

The focus of our research centers around the mechanism and regulation of mRNA biogenesis in Trypanosoma brucei. We are interested both in the molecular mechanisms of gene regulation and in how these mechanisms are integrated into interlocking circuits that ensure the orderly turning on and off of genes. In particular, we are interested at deciphering the potential function of modified nucleotides in the trypanosome metabolism (see C. Tschudi for further details) and the function and mechanism of RNA interference or RNAi, which refers to the post-transcriptional gene silencing mechanism whereby gene-specific double-stranded RNA (dsRNA) triggers degradation of its cognate mRNA. RNAi has been described in a variety of eukaryotic organisms from protozoa to animals, is mechanistically related to the phenomena of co-suppression in plants and "quelling" in Neurospora, and is considered a defense mechanism against harmful transcripts such as those produced during viral infection and mobilization of transposons.

Recent Publications

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Ullu E, Tschudi C, Chakraborty T. (2004) RNA interference in protozoan parasites. Cell Microbiol. Jun; 6(6):509-19. [Review]

He CY, Ho HH, Malsam J, Chalouni C, West CM, Ullu E, Toomre D, Warren G. (2004) Golgi duplication in Trypanosoma brucei. J Cell Biol. May 10; 165(3): 313-21.

Shi H, Djikeng A, Tschudi C, Ullu E. (2004) Argonaute protein in the early divergent eukaryote Trypanosoma brucei: control of small interfering RNA accumulation and retroposon transcript abundance. Mol Cell Biol. Jan; 24(1): 420-7.

Djikeng A, Shi H, Tschudi C, Shen S, Ullu E. (2003) An siRNA ribonucleoprotein is found associated with polyribosomes in Trypanosoma brucei. RNA. Jul 9(7):802-8.

Shi H, Wormsley S, Tschudi C, Ullu E. (2002) Efficient transposition of preformed synaptic Tn5 complexes in Trypanosoma brucei. Mol Biochem Parasitol. Apr 30; 121(1):141-4.

Djikeng A, Shi H, Tschudi C, Ullu E. (2001) RNA interference in Trypanosoma brucei: cloning of small interfering RNAs provides evidence for retroposon-derived 24-26-nucleotide RNAs. RNA. Nov; 7(11):1522-30.

Vanacova S, Tachezy J, Ullu E, Tschudi C. (2001) Unusual diversity in alpha-amanitin sensitivity of RNA polymerases in trichomonads. Mol Biochem Parasitol. Jul; 115(2): 239-47.

Shen S, Arhin GK, Ullu E, Tschudi C. (2001) In vivo epitope tagging of Trypanosoma brucei genes using a one step PCR-based strategy. Mol Biochem Parasitol. Mar; 113(1): 171-3.

Djikeng A, Ferreira L, D'Angelo M, Dolezal P, Lamb T, Murta S, Triggs V, Ulbert S, Villarino A, Renzi S, Ullu E, Tschudi C. (2001) Characterization of a candidate Trypanosoma brucei U1 small nuclear RNA gene. Mol Biochem Parasitol. Mar; 113(1): 109-15.

Shi H, Djikeng A, Mark T, Wirtz E, Tschudi C, Ullu E. (2000) Genetic interference in Trypanosoma brucei by heritable and inducible double-stranded RNA. RNA. Jul; 6(7): 1069-76.

Marchetti MA, Tschudi C, Kwon H, Wolin SL, Ullu E. (2000) Import of proteins into the trypanosome nucleus and their distribution at karyokinesis. J Cell Sci. Mar; 113( Pt 5): 899-906.