The new biology of Trypanosoma brucei: from transcriptomics to development
Trypanosoma brucei, the causative agent of sleeping sickness, undergoes a complex life cycle between the mammalian host and the blood-feeding tsetse fly vector (Diptera: Glossinidae), which among others involves changes in cell morphology, metabolism, signaling pathways and gene expression. Consequently, these parasites have evolved adaptations to allow for their survival in both the gut and salivary glands of the tsetse fly, as well as in the bloodstream of their mammalian host. One of the fundamental steps in the life of a pathogen is the acquisition of infectivity. In the case of African trypanosomes, this occurs in the tsetse fly. Although the intricate nature of trypanosome development in the fly has been recognized for more than a century, the molecular mechanisms are still mysterious, due to experimental challenges of studying parasites in the fly. By analyzing the transcriptome of trypanosomes derived from infected tsetse flies, we have recently succeeded in reproducing in the laboratory the developmental stages found in the insect vector, including the generation of infective metacyclics expressing the variant surface glycoprotein (VSG) coat. This experimental system has the potential to contribute towards developing new intervention strategies, including transmission blocking vaccines, which are currently being sought in other arthoropod-transmitted diseases as alternatives to conventional vaccines against pathogens.
Mining genomic information to expose new strategies to combat the diseases caused by African trypanosomes and related parasites
Identifying genes essential for survival in the host is fundamental toward unraveling the biology of human pathogens and understanding mechanisms of pathogenesis. Recent advances in genomics research are providing new avenues to a more holistic understanding of pathogens. We are using next-generation sequencing technologies and high-throughput proteomics to determine the coding capacity of the T. brucei and Leishmania braziliensis genomes and to expose gene expression landscapes that parasites use to adapt to different environments in their life cycle.
Chikne V, Gupta SK, Doniger T, K SR, Cohen-Chalamish S, Ben-Asher HW, Kolet L, Yahia NH, Unger R, Ullu E, Kolev NG, Tschudi C, Michaeli S: The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei. J Mol Biol. 2017 Apr 26; 2017 Apr 26. PMID: 28456523
Savage AF, Kolev NG, Franklin JB, Vigneron A, Aksoy S, Tschudi C: Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans. PLoS One. 2016; 2016 Dec 21. PMID: 28002435
Chikne V, Doniger T, Rajan KS, Bartok O, Eliaz D, Cohen-Chalamish S, Tschudi C, Unger R, Hashem Y, Kadener S, Michaeli S: A pseudouridylation switch in rRNA is implicated in ribosome function during the life cycle of Trypanosoma brucei. Sci Rep. 2016 May 4; 2016 May 4. PMID: 27142987
Ramey-Butler K, Ullu E, Kolev NG, Tschudi C: Synchronous expression of individual metacyclic variant surface glycoprotein genes in Trypanosoma brucei. Mol Biochem Parasitol. 2015 Mar-Apr; 2015 Apr 18. PMID: 25896436
Kolev NG, Ullu E, Tschudi C: Construction of Trypanosoma brucei Illumina RNA-Seq libraries enriched for transcript ends. Methods Mol Biol. 2015. PMID: 25388113
Eliaz D, Doniger T, Tkacz ID, Biswas VK, Gupta SK, Kolev NG, Unger R, Ullu E, Tschudi C, Michaeli S: Genome-wide analysis of small nucleolar RNAs of Leishmania major reveals a rich repertoire of RNAs involved in modification and processing of rRNA. RNA Biol. 2015; 2015 May 13. PMID: 25970223
Kolev NG, Ullu E, Tschudi C: The emerging role of RNA-binding proteins in the life cycle of Trypanosoma brucei. Cell Microbiol. 2014 Apr; 2014 Feb 16. PMID: 24438230
Ericson M, Janes MA, Butter F, Mann M, Ullu E, Tschudi C: On the extent and role of the small proteome in the parasitic eukaryote Trypanosoma brucei. BMC Biol. 2014 Feb 19; 2014 Feb 19. PMID: 24552149
Shi H, Barnes RL, Carriero N, Atayde VD, Tschudi C, Ullu E: Role of the Trypanosoma brucei HEN1 family methyltransferase in small interfering RNA modification. Eukaryot Cell. 2014 Jan; 2013 Nov 1. PMID: 24186950
Atayde VD, Shi H, Franklin JB, Carriero N, Notton T, Lye LF, Owens K, Beverley SM, Tschudi C, Ullu E: The structure and repertoire of small interfering RNAs in Leishmania (Viannia) braziliensis reveal diversification in the trypanosomatid RNAi pathway. Mol Microbiol. 2013 Feb; 2012 Dec 26. PMID: 23217017
Kolev NG, Ramey-Butler K, Cross GA, Ullu E, Tschudi C: Developmental progression to infectivity in Trypanosoma brucei triggered by an RNA-binding protein. Science. 2012 Dec 7. PMID: 23224556
Tschudi C, Shi H, Franklin JB, Ullu E: Small interfering RNA-producing loci in the ancient parasitic eukaryote Trypanosoma brucei. BMC Genomics. 2012 Aug 27; 2012 Aug 27. PMID: 22925482