Project description:Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites; information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries.
Project description:Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites; information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries. Two-condition experiment, Untreated vs.Treated B. divergens parasites, cultured in human erythrocytes. Treatment with a piperidinyl-benzimidizalone analogue. Biological replicates: 3 untreated (control) replicates, 3 treated replicates. The 6-sample dataset represents untreated(control) vs pooled_reference samples at various timepoints.
Project description:The study comprehends two consecutive LC-QqQ/MS analyses of Babesia divergens merozoite extracts isolated from B. divergens infected red blood cell cultures performed under identical chromatographic conditions and targeting distinct transitions corresponding to metabolites from specific pathways including the glycolysis, the TCA cycle, the pentose phosphate pathway, purine and pyrimidine biosynthesis and amino acid metabolism.
2020-12-16 | ST001878 | MetabolomicsWorkbench
Project description:Babesia divergens strain:Bd Rouen 1987 | cultivar:Babesia divergens human red blood cells culture
Project description:Babesia parasites transition between a mammalian host, where they cause babesiosis, and the tick vector that transmits them. This transition provides an environmental signal resulting in altered gene expression allowing the completion of the parasite’s life cycle. A comparison of the different life stages that occur within mammalian and tick hosts can provide insight into the adaptation of Babesia to these different environments. In this study, we used RNA-Seq to compare gene expression between Babesia bovis blood stages and tick derived kinetes.
Project description:Malarial rhythmic fevers are the consequence of the synchronous bursting of red blood cells (RBCs) upon completion of the malaria parasite asexual cell-cycle. Here we hypothesized that an intrinsic clock in the parasite underlies the modulo-24h rhythms of RBC bursting. We show that parasite rhythms are plastic and slow down to match rhythms of hosts with long circadian period. We also demonstrate that malaria rhythms persist even when host food intake is evenly spread across 24h, suggesting that host feeding cues are not required for synchrony. Moreover, we find that the parasite population remains synchronous and rhythmic even in an arrhythmic clock mutant host. Thus, we propose that parasite rhythms are generated by the parasite, possibly to anticipate its rhythmic changing environment.
Project description:In order to compare sponge and eumetazoan (higher animal) body plans, we identified and studied expression of a broad range of eumetazoan developmental regulatory genes in Sycon ciliatum (Calcispongiae). In this species, embryonic development is semi-synchronous within a population, synchronous within individuals, and oocytes and embryos occupy a significant fraction of the volume of the sponges during the reproductive period. RNASeq libraries representing non-reproductive (somatic) tissue slices along the body axis, as well as oocytes, embryos and free swimming larvae were generated from material obtained by sampling throughout the life cycle.
Project description:In order to compare sponge and eumetazoan (higher animal) body plans, we identified and studied expression of a broad range of eumetazoan developmental regulatory genes in Sycon ciliatum (Calcispongiae). In this species, embryonic development is semi-synchronous within a population, synchronous within individuals, and oocytes and embryos occupy a significant fraction of the volume of the sponges during the reproductive period. RNASeq libraries representing non-reproductive (somatic) tissue slices along the body axis, as well as oocytes, embryos and free swimming larvae were generated from material obtained by sampling throughout the life cycle.