ABSTRACT: Metabolite profiling across the 1st and 2nd intraerythrocytic developmental lifecycles of the malaria parasite P. falciparum following induction of delayed death with indolmycin treatment
Project description:The lack of a comprehensive map of transcription start sites (TSS) across P. falciparum genome has hampered advances in decrypting the molecular mechanisms underlying regulation of gene expression in the malaria parasite. In eukaryotic model organisms, development of genome-wide approaches and next-generation sequencing technologies has contributed to a better understanding of the impact of local nucleotide composition on transcriptional regulation. Using such methods, we generated a single nucleotide-resolution map of transcription initiation events during P. falciparum intra-erythrocytic developmental cycle. Examination of transcription start site during the intra-erythorcytic development of the human parasite Plasmodium falciparum
Project description:This experiment characterizes the transcriptome of the human malaria parasite, P. falciparum at 8 different stages of the intraerythrocytic cycle
Project description:This experiment characterizes the transcriptome of the human malaria parasite, P. falciparum at 8 different stages of the intraerythrocytic cycle Examination of polyA selected RNA in Plasmodium falciparum 3D7 strain at 8 different stages using RNA-seq
Project description:The high prevalence of sickle cell disease in some human populations likely results from the protection afforded against severe Plasmodium falciparum malaria and death by heterozygous carriage of HbS. P. falciparum remodels the erythrocyte membrane and skeleton, displaying parasite proteins at the erythrocyte surface that interact with key human proteins in the Ankyrin R and 4.1R complexes. Oxidative stress generated by HbS, as well as by parasite invasion, disrupts the kinase/phosphatase balance, potentially interfering with the molecular interactions between human and parasite proteins. HbS is known to be associated with abnormal membrane display of parasite antigens. Studying the proteome and the phosphoproteome of red cell membrane extracts from P. falciparum infected and non-infected erythrocytes, we show here that HbS heterozygous carriage, combined with infection, modulates the phosphorylation of erythrocyte membrane transporters and skeletal proteins as well as of parasite proteins. Our results highlight modifications of Ser- /Thr- and/or Tyr- phosphorylation in key human proteins, such as ankyrin, β-adducin, β-spectrin and Band 3, and key parasite proteins, such as RESA or MESA. Altered phosphorylation patterns could disturb the interactions within membrane protein complexes, affect nutrient uptake and the infected erythrocyte cytoadherence phenomenon, thus lessening the severity of malaria symptoms.
Project description:In order to further our understanding of the metabolic network of the malaria parasite, Plasmodium falciparum, we carried out a concurrent transcriptomic and metabolomic study of the parasite's intraerythrocytic developmental cycle. These microarray data were generated to compare the expression levels of metabolic enzymes to the concentrations of their associated metabolites over the 48-hour life cycle.
Project description:The lack of a comprehensive map of transcription start sites (TSS) across P. falciparum genome has hampered advances in decrypting the molecular mechanisms underlying regulation of gene expression in the malaria parasite. In eukaryotic model organisms, development of genome-wide approaches and next-generation sequencing technologies has contributed to a better understanding of the impact of local nucleotide composition on transcriptional regulation. Using such methods, we generated a single nucleotide-resolution map of transcription initiation events during P. falciparum intra-erythrocytic developmental cycle.
Project description:This experiment characterizes the localisation of H2A.Z, H3K9ac and H3K4me3 in the epigenome of the human malaria parasite, P. falciparum at 4 different stages of intraerythrocytic development.
Project description:To investigate the accumulation of non coding small RNAs we performed high throughput RNA sequencing on size selcted total RNA from malaria parasite Plasmodium falciparum
Project description:Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain microcirculation is a hallmark of cerebral malaria (CM), leading to endothelial activation, microvascular occlusion, brain swelling, and death. The inflammatory pathogenesis is however poorly understood, partly due to the lack of suitable in vitro platforms to study CM biology. Here, we used 3D perfusable brain microvessels to investigate combinatorial pathogen and host inflammatory stimuli over the in situ parasite maturation and IE rupture. Whereas tumor necros factor (TNF) potently upregulated adhesion molecules and inflammatory pathways, and uniformly recruited leukocytes throughout the microvessels, P. falciparum-IEs upregulated unique stress response pathways, induced minor junctional disturbances and low levels of endothelial apoptosis, and preferentially recruited leukocytes at IE binding regions. Furthermore, parasites delayed recovery from TNF stimulation and enhanced inflammatory responses. Our findings offer insights into CM biology, and suggest that multiple events intersect to promote brain barrier inflammation in CM.