Publications by authors named "Julian Rayner"

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Successful transmission of Plasmodium falciparum from one person to another relies on the complete intraerythrocytic development of non-pathogenic sexual gametocytes infectious for anopheline mosquitoes. Understanding the genetic factors that regulate gametocyte development is vital for identifying transmission-blocking targets in the malaria parasite life cycle. Toward this end, we conducted a forward genetic study to characterize the development of gametocytes from sexual commitment to mature stage V.

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Malaria pathogenesis and parasite multiplication depend on the ability of Plasmodium merozoites to invade human erythrocytes. Invasion is a complex multi-step process involving multiple parasite proteins which can differ between species and has been most extensively studied in P. falciparum.

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The impact of cerebral malaria on the transcriptional profiles of cerebral tissues is difficult to study using noninvasive approaches. We isolated plasma extracellular vesicles (EVs) from patients with cerebral malaria and community controls and sequenced their mRNA content. Deconvolution analysis revealed that EVs from cerebral malaria are enriched in transcripts of brain origin.

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Challenges in classifying recurrent Plasmodium vivax infections constrain surveillance of antimalarial efficacy and transmission. Recurrent infections may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or reinfection. Molecular inference of familial relatedness (identity-by-descent or IBD) can help resolve the probable origin of recurrences.

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In 2004 the first annual BioMalPar meeting was held at EMBL Heidelberg, bringing together researchers from around the world with the goal of building connections between malaria research groups in Europe. Twenty years on it is time to reflect on what was achieved and to look ahead to the future.

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Background: The Dantu blood group variant protects against P. falciparum infections but its wider consequences have not been previously explored. Here, we investigate the impact of Dantu on susceptibility to bacteraemia.

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The interaction of Plasmodium falciparum-infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is an exported P. falciparum protein involved in iRBC remodelling, which is essential for the formation of protrusions or "knobs" on the iRBC surface.

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parasites have a complex life cycle, but the most clinically relevant stage of the disease is the invasion of erythrocytes and the proliferation of the parasite in the blood. The influence of human genetic traits on malaria has been known for a long time, however understanding the role of the proteins involved is hampered by the anuclear nature of erythrocytes that makes them inaccessible to genetic tools. Here we overcome this limitation using stem cells to generate erythroid cells with an differentiation protocol and assess parasite invasion with an adaptation of flow cytometry to detect parasite hemozoin.

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Ethiopia has the greatest burden of Plasmodium vivax in Africa, but little is known about the epidemiological landscape of parasites across the country. We analysed the genomic diversity of 137 P. vivax isolates collected nine Ethiopian districts from 2012 to 2016.

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Article Synopsis
  • Scientists are studying tiny bubbles (called extracellular vesicles) from the malaria parasite Plasmodium falciparum that carry RNA.
  • They found that the RNA released in these bubbles is different in timing and content compared to the RNA inside the parasite.
  • The RNA in the bubbles may help control how the parasite’s genes work, which could be important for keeping the parasite healthy and alive.
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Round table discussion on challenges and opportunities in malaria research with Elena Levashina, Dominique Soldati-Favre, Andrew Waters, Friedrich Frischknecht, and Julian Rayner.

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Article Synopsis
  • - Tryptophan Rich Antigens (TRAgs) are a group of proteins found in all Plasmodium species, but they're especially abundant in P. vivax and related parasites, and they play a role in the invasion of red blood cells.
  • - Scientists discovered that the TRAg PVP01_0000100 binds to reticulocytes through its C-terminal tryptophan-rich domain, which was structurally analyzed using X-ray crystallography and found to resemble lipid-binding domains.
  • - The study shows that PVP01_0000100 has a preference for binding sulfatide, a lipid found in cell membranes, and that its equivalent in P. knowlesi is crucial for the parasite
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Our overall understanding of the developmental biology of malaria parasites has been greatly enhanced by recent advances in transcriptomic analysis. However, most of these investigations rely on laboratory strains (LS) that were adapted into culture many years ago, and the transcriptomes of clinical isolates (CI) circulating in human populations have not been assessed. In this study, RNA-seq was used to compare the global transcriptome of mid-stage gametocytes derived from three short-term cultured CI, with gametocytes derived from the NF54 reference laboratory strain.

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BACKGROUNDThe biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate of P.

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Introduction: The true nature of the population spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations is often not fully known as most cases, particularly in Africa, are asymptomatic. Finding the true magnitude of SARS-CoV-2 spread is crucial to provide actionable data about the epidemiological progress of the disease for researchers and policymakers. This study developed and optimized an antibody enzyme-linked immunosorbent assay (ELISA) using recombinant nucleocapsid antigen expressed in-house using a simple bacterial expression system.

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Background: The long co-evolution of and has resulted in the selection of numerous human genetic variants that confer an advantage against severe malaria and death. One such variant is the Dantu blood group antigen, which is associated with 74% protection against severe and complicated malaria infections in homozygous individuals, similar to that provided by the sickle haemoglobin allele (HbS). Recent studies suggest that Dantu exerts this protection by increasing the surface tension of red blood cells, thereby impeding the ability of merozoites to invade them and reducing parasite multiplication.

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Transmission of the deadly malaria parasite Plasmodium falciparum from humans to mosquitoes is achieved by specialized intraerythrocytic sexual forms called gametocytes. Though the crucial regulatory mechanisms leading to gametocyte commitment have recently come to light, networks of genes that control sexual development remain to be elucidated. Here, we report a pooled-mutant screen to identify genes associated with gametocyte development in P.

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Introduction: Detailed analyses of genetic diversity, antigenic variability, protein localization and immunological responses are vital for the prioritization of novel malaria vaccine candidates. Comprehensive approaches to determine the most appropriate antigen variants needed to provide broad protection are challenging and consequently rarely undertaken.

Methods: Here, we characterized PF3D7_1136200, which we named Asparagine-Rich Merozoite Antigen (ARMA) based on the analysis of its sequence, localization and immunogenicity.

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The antimalarial activity of the frontline drug artemisinin involves generation of reactive oxygen species (ROS) leading to oxidative damage of parasite proteins. To achieve homeostasis and maintain protein quality control in the overwhelmed parasite, the ubiquitin-proteasome system kicks in. Even though molecular markers for artemisinin resistance like have been identified, the intricate network of mechanisms driving resistance remains to be elucidated.

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Challenges in understanding the origin of recurrent infections constrains the surveillance of antimalarial efficacy and transmission of this neglected parasite. Recurrent infections within an individual may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or new inoculations (reinfection). Molecular inference of familial relatedness (identity-by-descent or IBD) based on whole genome sequence data, together with analysis of the intervals between parasitaemic episodes ("time-to-event" analysis), can help resolve the probable origin of recurrences.

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We describe the MalariaGEN Pf7 data resource, the seventh release of genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.

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Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission.

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Article Synopsis
  • Scientists discovered that some malaria parasites are becoming resistant to a treatment called artemisinin combination therapies (ACTs), making it harder to fight the disease.
  • They focused on a special mutant parasite that reacts differently to the treatment and found a gene called KIC5 that might help the parasite survive the medicine.
  • By studying how this gene works, researchers hope to learn more about why the parasites can resist treatment and how to fight them better.
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Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P.

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