African Sleeping Sickness

Parasitic protozoa are a major cause of global infectious diseases and thus, represent one of the most serious threats to public health. Among these are African trypanosomes, the causative agents of African trypanosomiasis or sleeping sickness in humans (HAT) and a wasting and fatal disease (Nagana) in cattle, domestic pigs and other farm animals. Although the encouraging news is that HAT has been declining in recent years, livestock infections remain prevalent and have a profound effect on economic development in afflicted regions. Still, the impact of HAT is high, due to treatment costs, high morbidity and mortality and current drugs suffer from toxicity and emerging resistance. Approximately 5% of patients receiving melarsoprol die from the treatment and eflornithine is less toxic, but challenging to administer in resource-limited settings. Relapse occurs in up to 30 percent of the individuals. Nonetheless, without treatment, trypanosome infections are always fatal. Thus, further understanding of the biology of the parasite is a crucial route towards finding new therapeutic solutions for this and related diseases.

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.


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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

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

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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

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