Project description:Trypanosoma brucei gambiense is the causative agent of the fatal human disease African sleeping sickness. Using Digital Gene Expression we have compared the transcriptome of two T.b.brucei (STIB 247)xT.b.gambiense (STIB386) hybrids.
Project description:Trypanosoma brucei gambiense is the causative agent of the fatal human disease African sleeping sickness. Using Digital Gene Expression we have compared the transcriptome of a group 1 T.b.gambiense (Eliane) and a T.b.brucei (STIB 247).
Project description:Trypanosoma brucei gambiense is the causative agent of the fatal human disease African sleeping sickness. Using Digital Gene Expression we have compared the transcriptome of two isogenic T.b.gambiense lines that are either sensitive or resistant to human serum.
Project description:Trypanosoma brucei gambiense is the causative agent of the fatal human disease African sleeping sickness. Here we have compared the transcriptome of two different life cycle stages, the potentially human-infective bloodstream form and the non-human-infective procyclic stage, using digital gene expression (DGE) analysis.
Project description:Trypanosoma brucei gambiense is the causative agent of the fatal human disease African sleeping sickness. Here we have compared the transcriptome of two different life cycle stages, the potentially human-infective bloodstream form and the non-human-infective procyclic stage, using digital gene expression (DGE) analysis. Digital gene expression analysis was performed on RNA from 3 biological replicates of bloodstream cultured T.b. gambiense strain STIB 386 and compared to that from 3 biological replicates of procyclic cultured T.b. gambiense strain STIB 386.
Project description:G-quadruplexes (G4s) are non-canonical DNA structures formed in guanine-rich sequences that are proposed to act as regulatory elements in trypanosomatid parasites, including Trypanosoma brucei, the causative agent of African sleeping sickness. However, their functional roles remain poorly understood, largely due to limited knowledge of their genomic distribution. Herein, we performed in silico analyses across 64 trypanosomatid species uncovering high degree of variability in G4 prevalence and species-specific patterns. We generated the first chromatin-based, genome-wide G4 map in T. brucei using G4 chromatin immunoprecipitation followed by sequencing (G4 ChIP-Seq), revealing enrichment within gene-associated regions, including coding DNA sequences (CDSs), and transcription boundaries such as transcription start sites (TSSs) and transcription termination sites (TTSs). This pattern diverges markedly from previous genome-wide G4 maps in humans, suggesting that G4s may play roles unique to trypanosome biology. To investigate their functional relevance, we profiled the transcriptome of T. brucei upon treatment with the G4-stabilizing ligand PhenDC3. PhenDC3 induced targeted transcriptional perturbation of genes bearing G4s, particularly those located within CDSs and TSSs. Altogether, our findings highlight a distinctive role for G4s in regulating gene expression in T. brucei and support their potential as therapeutic targets in the treatment of African sleeping sickness.
Project description:G-quadruplexes (G4s) are non-canonical DNA structures formed in guanine-rich sequences that are proposed to act as regulatory elements in trypanosomatid parasites, including Trypanosoma brucei, the causative agent of African sleeping sickness. However, their functional roles remain poorly understood, largely due to limited knowledge of their genomic distribution. Herein, we performed in silico analyses across 64 trypanosomatid species uncovering high degree of variability in G4 prevalence and species-specific patterns. We generated the first chromatin-based, genome-wide G4 map in T. brucei using G4 chromatin immunoprecipitation followed by sequencing (G4 ChIP-Seq), revealing enrichment within gene-associated regions, including coding DNA sequences (CDSs), and transcription boundaries such as transcription start sites (TSSs) and transcription termination sites (TTSs). This pattern diverges markedly from previous genome-wide G4 maps in humans, suggesting that G4s may play roles unique to trypanosome biology. To investigate their functional relevance, we profiled the transcriptome of T. brucei upon treatment with the G4-stabilizing ligand PhenDC3. PhenDC3 induced targeted transcriptional perturbation of genes bearing G4s, particularly those located within CDSs and TSSs. Altogether, our findings highlight a distinctive role for G4s in regulating gene expression in T. brucei and support their potential as therapeutic targets in the treatment of African sleeping sickness.
Project description:African trypanosomes, the causative agents of Human and Animal African trypanosomiasis or sleeping sickness, reside in tissue niches proposed to be important for disease outcome and transmission. Here, we demonstrate that parasites in the inguinal white adipose tissue (iWAT) niche induce sexually dimorphic physiological and immunological responses. Following chronic Trypanosoma brucei infection, male mice experience weight loss, reduced adipose tissue mass and altered tissue function, as well as changes in feeding behaviour, whereas females do not. We identified that interleukin-17 (IL-17), a cytokine that we show is elevated in sleeping sickness patients, orchestrates a sex-specific response to T. brucei infection in experimental infections. Deletion of murine IL-17a/f abolishes infection-associated weight loss, alters feeding behaviour, and limits adipose tissue wasting in male mice only. We propose that these effects might be triggered locally in adipocytes via engagement of IL-17 with its cognate receptor leading to lipolysis and tissue wasting, and/or systemically, via IL-17 signalling in the hypothalamus, potentially suggesting that IL-17 signalling coordinates brain-adipose tissue communication during sleeping sickness. Our findings also suggest a key sex-dependent role for the IL-17 isoforms IL-17A and IL-17F in regulating adipose tissue and energy balance during infection. Altogether, the results presented here open new directions to understand energy balance and brain-adipose tissue communication during chronic infection.