Project description:Plasmodium falciparum secretes extracellular vesicles that contain RNA. The biological benefit of this secretion to the secreting parasite is not known. Here, we sequenced the RNA content of extracellular vesicles and compared with that of the secreting whole parasites. The data suggests that extracellular vesicles might be part of a post-transcriptional regulatory mechanism that shapes intracellular RNA levels in the parasite.
Project description:The role of extracellular vesicles in developing artemisinin resistance in Plasmodium falciparum is not known. We have posited a role for EVs in the development of ARTr (EVs export hypothesis) (Tandoh et al.,2022).The objective of this study was to test a prediction of the EVs export hypothesis to gain insight into a putative role for EVs in the expression of the artemisinin resistant phenotype. We compared the gene expression profile of two artemisinin resistant parasites (C580R and R539T) generated by CRISPR based editing of an artemisinin susceptible parasite (Dd2) for enrichment with an EVs module of interest using gene set enrichment analysis.
Project description:We sequenced the RNA content of circulating extracellular vesicles obtained from retinopathy- positive (CM-R⁺) and negative cerebral malaria (CM-R⁻) patients and community controls (CC) without Plasmodium falciparum infection. We found that some of the transcripts enriched in circulating extracellular vesicles are highly expressed in the brain compared to other tissues and could have a diagnostic potential in the cerebral malaria context.
Project description:Transcriptome-module phenotype association study implicates extracellular vesicles biogenesis in Plasmodium falciparum artemisinin resistance
Project description:Recent studies indicate that the human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by Plasmodium vivax. Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the P. vivax spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into P. falciparum 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named P. vivax Spleen-Dependent Protein 1 (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from P. vivax-infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in P. vivax, a major challenge for malaria elimination.
Project description:RNAseq data profiling the artemisinin-sensitive P. falciparum piggyBac mutant of the PF3D7_1136600 gene (conserved Plasmodium gene, unknown function)
Project description:Background: There is some evidence demonstrating the effect of psychological interventions in improvements in health biological parameters. To best of our knowledge, no study had addressed the impact of any psychological intervention on extracellular vesicles. In addition, Mindfulness-Based Cognitive Therapy (MBCT) and Emotion Focused Therapy for Cancer Recovery (EFT-CR) in the group have never been explored regarding extracellular vesicles and the effectiveness of these was not compared yet.
Objectives:
1. To explore and compare the effect of MBCT and EFT-CR on biological parameters and psychological variables in distressed people who have had breast, prostate and colorectal cancer;
2. In addition, we will explore the acceptability through recruitment and retention rates of MBCT and EFT-CR in group and evaluate whether these interventions are appropriate for a larger clinical trial.
Methods: The design of this study is a parallel randomized controlled trial. Participants will be randomized into MBCT, EFT-CR or usual care. Outcome measures will be assessed before, at the end of the intervention (8 weeks) and follow-ups (24 and 52 weeks from the baseline moment).
Hypotheses: The researchers expected that both interventions will have an effect on extracellular vesicles and other study biomarkers as well as improvements in psychological outcomes, compared to treatment as usual (TAU) group. Regarding the comparative effectiveness, we did not have evidence to hypothesize which one of the interventions will be superior in both biological (extracellular vesicles) and psychological outcomes.
Contribution for practice: The results of this preliminary study would permit to know if there are benefits of these psychological interventions on changes in extracellular vesicles and on psychological outcomes related to health. In addition, this study will permit to determine the acceptability of conducting a larger randomized controlled trial.
Project description:Transcriptomic Analysis of Cultured Sporozoites of P. falciparum RNA-seq reads from each of three developmental stages (2 replicates per sample) were mapped to the reference Plasmodium falciparum genome, and gene expression levels were calculated for each sample.