Yale School of Medicine

Internal Medicine

Internal Medicine, Yale School of Medicine

Internal Medicine
333 Cedar Street
Room LMP-1072
P.O. Box 208056
New Haven, CT 06520-8056

Elisabetta Ullu, Ph.D.

Elisabetta Ullu, Ph.D.

Professor of Medicine and Cell Biology
Joint Appointment with Cell Biology

Research Interests

RNA interference and gene regulation in the human parasite Trypanosoma brucei

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 they have attained the status of model systems for eukaryotic pathogens. The genome sequence of Trypanosoma brucei is completed. In addition, these organisms are easily amenable to genetic manipulations and can be grown in axenic cultures in large quantities. Because trypanosomes are ancient eukaroytic organisms, which separated very early from the main branch of the eukaryotic lineage, their biology 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 on two main topics; 1. the mechanism and biological significance of the process of RNA interference, a powerful gene silencing mechanism that is widespread among eukaryotes and function to mantain genome stability and to regulate development. 2. The process of mRNA biogenesis in Trypanosoma brucei (from transcription to translation see Christian Tschudi for more details).

Education

Laurea in Biological Sciences, University of Rome (Italy), 1973

Fellowship: European Molecular Biology Laboratory (Heidelberg, Germany) and Yale University.

Members of the Research Group

Co-Principal Investigator

Christian Tschudi

Postdoctoral fellows

George Arhin
Nathalie Chamond
Jeff Rouan

Graduate Students

Hongjie Li
Kristin Patrick

Research Associate

Huafang Shi

Research Assistant

Sarah Renzi
Irene Tong

Recent Publications

  • Tschudi, C. and Ullu, E. (1990). Destruction of U2, U4, or U6 small nuclear RNA blocks trans-splicing in trypanosome cells. Cell 61, 459-466.
  • Ullu, E. and Tschudi, C. (1991). Trans-splicing in trypanosomes requires methylation of the 5' end of the spliced leader RNA. Proc. Natl. Acad. Sci. USA 88, 10074-10078. [Medline Abstract]
  • Ullu, E., Matthews, K. and Tschudi, C. (1993). Temporal order of RNA processing reactions in trypanosomes: rapid trans-splicing precedes polyadenylation of newly-synthesized tubulin transcripts. Mol. Cell. Biol. 13, 720-725. [Medline Abstract]
  • Matthews, K.R., Tschudi, C. and Ullu, E. (1994) A common pyrimidine-rich motif governs trans-splicing and polyadenylation of tubulin polycistronic pre-mRNA in trypanosomes. Genes & Development, 8, 491-501. [Medline Abstract]
  • Tschudi, C. and Ullu, E. (1994) Trypanosomatid protozoa provide paradigms of eukaryotic biology. Inf. Agents and Disease 3, 181-186.

  • Nakaar, V., Tschudi, C. and Ullu, E. (1995). An unusual liaison: small nuclear and cytoplasmic RNA genes team up with tRNA genes in trypanosomatid protozoa. Parasitology Today 11, 225-228.
  • Gunzl, A., Tschudi, C., Naakar, V. and Ullu, E. (1995). Accurate transcription of the Trypanosoma brucei U2 snRNA gene in a homologous extract. J. Biol. Chem. 270, 17287-17291. [Medline Abstract]
  • Ullu, E. and Tschudi, C. (1995). Accurate modification of the trypanosome spliced leader cap structure in a homologous cell-free extract. J. Biol. Chem. 270, 20365-20369. [Medline Abstract]
  • Silva, E., Ullu, E., Kobayashi, R. and Tschudi, C. (1998). Trypanosome capping enzymes display a novel two-domain structure. Mol. Cell. Biol., 18, 4612-4619. [Medline Abstract]
  • Ngô, H., Tschudi, C., Gull, K. and Ullu, E. Double-stranded RNA induces mRNA degradation in Trypanosoma brucei. Proc. Natl. Acad. Sci. USA, 95, 14687-14692 (1998).
  • Mair, G., Shi, H., Li, H., Djikeng, A., Aviles, H.O., Bishop, J.R., Falcone, F.H., Gavrilescu, C., Montgomery, J.L., Santori, M.S., Stern, L.S., Wang., Z., Ullu, E. and Tschudi, C. (2000). A new twist in trypanosome RNA metabolism: cis-splicing of pre-mRNA. RNA, 6, 163-169.
  • Marchetti, M.A., Tschudi, C., Kwon, H., Wolin, S.L. and Ullu, E. (2000). Import of proteins into the trypanosome nucleus and their distribution at karyokinesis. J. Cell Science, 113, 899-906.
  • Shi, H., Djikeng, A., Mark, T., Wirtz, E. Tschudi, C. and Ullu, E. (2000). Genetic interference in Trypanosoma brucei by heritable and inducible double-stranded RNA. RNA, 6, 1069-1076.
  • Mair, G., Ullu, E. and Tschudi, C. (2000). Cotranscriptional cap 4 formation on the Trypanosoma brucei spliced leader RNA. J. Biol. Chem., 275, 28994-28999.
  • Djikeng, A., Shi, H., Tschudi, C. and Ullu, E. (2001). RNA interference in Trypanosoma brucei: cloning of small interfering RNAs provides evidence for retroposon-derived 24-26-nucleotide RNAs. RNA, 7, 1522-1530.
  • Liu, L., Liang, X.H., Uliel, S., Unger, R., Ullu, E. and Michaeli, S. (2002). RNA interference of signal peptide-binding protein SRP54 elicits deleterious effects and protein sorting defects in trypanosomes. J. Biol. Chem. 277, 47348-4757.
  • Mandelboim, M., Lopez Estraño, C., Tschudi, C., Ullu, E., and Michaeli, S. (2002). On the role of exon and intron sequences in trans-splicing utilization and cap 4 modification of the trypanosomatid Leptomonas collosoma SL RNA. J. Biol. Chem., 277, 35210-35218.
  • Djikeng, A., Shi, H., Tschudi, C., Shen, S. and Ullu E. (2003). An siRNA ribonucleoprotein is found associated with polyribosomes in Trypanosoma brucei. RNA 9, 802-808.
  • Shi, H., Djikeng, A., Tschudi, C. and 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., 24, 420-427.
  • Ullu, E. Tschudi, C, and Chakraborty, T. RNA interference in protozoan parasites. (2004) Cell. Microbiology. 6, 509-519
  • Arhin,G.K., Shen, S., Irmer, H., Ullu, E. and Tschudi, C. (2004). Role for a 300 kDa nuclear complex in the maturation of Trypanosoma brucei initiator methionyl-tRNA. Eukaryotic Cell, 3, 893-899.
  • Ruan, J., Arhin, G.K., Ullu, E. and Tschudi, C. (2004). Functional characterization of a Trypanosoma brucei TATA-binding protein-like factor points to a universal regulator of transcription in trypanosomes. Mol. Cell. Biol., 24, 9610-9618.
  • Shi, H., Chamond, N., Tschudi, C. and Ullu, E. (2004) Selection and characterization of RNAi-deficient trypanosomes impaired in target mRNA degradation. Eukaryotic Cell,6, 1445-53.
  • Shi, H., Ullu, E. and Tschudi, C. (2004). Function of the trypanosome Argonaute 1 protein in RNA interference requires the N-terminal RGG domain and arginine 735 in the Piwi domain. J. Biol. Chem., 279, 49889-93.
  • Elisabetta Ullu, Hugo, D., Lujan, and Christian Tschudi (2005)
  • Small sense and antisense RNAs derived from a telomeric retroposon family in Giardia intestinalis. Eukaryotic Cell (in press)

Contact

Campus Address
BCMM 136D

E-mail
elisabetta.ullu@yale.edu

Office Phone
(203) 785-3563

Fax
(203) 785-7329