The Hajduk laboratory is mainly interested in the molecular biology and biochemistry of trypanosomes, the causative agent of an human African sleeping sickness. Our studies address several basic molecular processes in these important pathogens to gain a better insight into the basic biology of these organisms and to explore new approaches for intervention of disease.
RNA Editing. Many trypanosome mitochondrial mRNAs are edited by the insertion or deletion of uridines at specific sites to create open reading frames for essential mitochondrial proteins. We are investigating the mechanism of RNA editing and the assembly of proteins and RNAs required for editing. In addition, we are studying the function of proteins produced by alternative mRNA editing which generates extensive protein diversity in these organisms.
tRNA Trafficking. All trypanosome mitochondrial tRNAs are encoded by nuclear genes and to carry out mitochondrial protein synthesis at least 20 tRNAs are imported from the cytoplasm. We have developed in vitro and in vivo assays to study the biochemical requirements and the RNA sequences or structures required for RNA import into mitochondria. In addition, we have begun the purification and proteomic analysis of the mitochondrial tRNA translocon.
Innate Immunity to Trypanosomes. Innate immunity can play an important role in preventing or limiting the effects of a parasitic infection. We are particularly interested in the biochemical and molecular basis for the non-immune killing of African trypanosomes. Trypanosoma brucei is the causative agent of a bovine disease Nagana, and is killed by a toxic subspecies of human serum high-density lipoproteins (HDL) while the human sleeping sickness parasites, T. gambiense and T . rhodesiense are not.
- Widener, J., Nielsen, M., Shiflett, A. Moestrup, S. and Hajduk S. (2007) Hemoglobin is a co-factor for trypanosome lytic factor. PLoS Pathogens
- Ochsenreiter, T. Cipriano, M. and Hajduk, S.L. (2007) KISS: The Kinetoplastid Editing Sequence Search Tool. RNA 13, 1-4.
- Hans, J., Marchewka, M., Hajduk, S.L. and S. Madison-Antenucci (2007) Role of RNA-Editing Associate Protein-1: Null mutants reveal link to mitochondrial RNA stability. RNA 13, 881-889.
- Ochsenreiter, T. and Hajduk, S.L. (2006) Alternative editing of mRNA generates protein diversity. EMBO Reports 7, 1128-1133.
- Oli MW, Cotlin LF, Shiflett AM, Hajduk, SL. (2006) Serum resistance-associated protein blocks lysosomal targeting of trypanosome lytic factor in Trypanosoma brucei. Eukaryot Cell. 5,132-9.
- Golden D.E. and Hajduk, S.L. (2006) The importance of RNA structure in RNA editing and a potential proofreading mechanism for correct guide RNA:pre-mRNA binary complex formation. J. Molec. Biol. 359, 585-596.
- Faulkner, S.D., Oli, M.W., Kieft, R., Cotlin, L., Widener, J., Shiflett, A., Cipriano, M.J., Pacocha, S.E., Birkeland, S.R., Hajduk, S.L., and McArthur, A.G. (2006) In vitro generation of human HDL resistant Trypanosoma brucei brucei. Eukaryot. Cell 5, 1276-1286.
- Golden, D.E. and Hajduk, S.L. (2005) The 3¢ untranslated region of cytochrome oxidase II mRNA functions in RNA editing of African trypanosomes exclusively as a cis guide RNA. RNA 11, 29-37.
- Shiflett, A.M., Bishop, J.R., Pahwa, A. and Hajduk, S.L. (2005) Human HDLs are multi-component innate immune complexes. J Biol Chem. 280, 32578-85.