Abstract

African trypanosomes are parasites of great medical and veterinary importance and useful for the study of the organization of the mitochondrial genome, regulation of mitochondrial gene expression and mutant mitochondrial DNA alteration. I propose to complete the cloning of the remaining 20% of the maxicircle DNA of T. brucei. These sequences and previously cloned maxicircle sequence will be employed to examine the detailed sequence organization of the maxicircle. Many cloned minicircles will be examined to determine minicircle sequence organization and sequence relationships among minicircles. The transcriptional organization of the maxicircle will be established. Bloodstream and culture form trypanosome maxicircle will be compared in order to elucidate the mechanism of regulation of mitochondrial (maxicircle) gene expression. Dyskinetoplastic (Dk) mutants will be examined using cloned kDNA (maxi- and mini-circle) probes. The loss or retention of specific maxicircle sequences and the alteration of specific kDNA sequence will be established in these mutants. Transcription of kDNA sequences in DK mutants will also be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI014102-10
Application #
3125637
Study Section
(SSS)
Project Start
1978-09-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Cestari, Igor; Anupama, Atashi; Stuart, Kenneth (2018) Inositol polyphosphate multikinase regulation of Trypanosoma brucei life stage development. Mol Biol Cell 29:1137-1152
Cestari, Igor; Stuart, Ken (2018) Transcriptional Regulation of Telomeric Expression Sites and Antigenic Variation in Trypanosomes. Curr Genomics 19:119-132
Carnes, Jason; McDermott, Suzanne M; Stuart, Kenneth (2018) RNase III Domain of KREPB9 and KREPB10 Association with Editosomes in Trypanosoma brucei. mSphere 3:
Carnes, Jason; McDermott, Suzanne; Anupama, Atashi et al. (2017) In vivo cleavage specificity of Trypanosoma brucei editosome endonucleases. Nucleic Acids Res 45:4667-4686
McDermott, Suzanne M; Stuart, Kenneth (2017) The essential functions of KREPB4 are developmentally distinct and required for endonuclease association with editosomes. RNA 23:1672-1684
Cestari, Igor; Haas, Paige; Moretti, Nilmar Silvio et al. (2016) Chemogenetic Characterization of Inositol Phosphate Metabolic Pathway Reveals Druggable Enzymes for Targeting Kinetoplastid Parasites. Cell Chem Biol 23:608-617
McDermott, Suzanne M; Luo, Jie; Carnes, Jason et al. (2016) The Architecture of Trypanosoma brucei editosomes. Proc Natl Acad Sci U S A 113:E6476-E6485
McDermott, Suzanne M; Carnes, Jason; Stuart, Kenneth (2015) Identification by Random Mutagenesis of Functional Domains in KREPB5 That Differentially Affect RNA Editing between Life Cycle Stages of Trypanosoma brucei. Mol Cell Biol 35:3945-61
McDermott, Suzanne M; Guo, Xuemin; Carnes, Jason et al. (2015) Differential Editosome Protein Function between Life Cycle Stages of Trypanosoma brucei. J Biol Chem 290:24914-31
Carnes, Jason; Anupama, Atashi; Balmer, Oliver et al. (2015) Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty. PLoS Negl Trop Dis 9:e3404

Showing the most recent 10 out of 109 publications