A new mass spectral library for high-coverage and reproducible analysis of the Plasmodium falciparum-infected red blood cell proteome.

Background: Plasmodium falciparum causes the majority of malaria mortality worldwide, and the disease occurs during the asexual red blood cell (RBC) stage of infection. In the absence of an effective and available vaccine, and with increasing drug resistance, asexual RBC stage parasites are an important research focus. In recent years, mass spectrometry-based proteomics using data-dependent acquisition has been extensively used to understand the biochemical processes within the parasite.

Post-Genomic Approaches to Understanding Malaria Parasite Biology: Linking Genes to Biological Functions.

are evolutionarily distant from model eukaryotes, and as a consequence they exhibit many non-canonical cellular processes. In the post-genomic era, functional "omics" disciplines (transcriptomics, proteomics, and metabolomics) have accelerated our understanding of unique aspects of the biology of malaria parasites. Functional "omics" tools, in combination with genetic manipulations, have offered new opportunities to investigate the function of previously uncharacterized genes.

Mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues.

The malaria-causing blood stage of Plasmodium falciparum requires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the parasite by targeting CoA biosynthesis/utilisation.

A high parasite density environment induces transcriptional changes and cell death in Plasmodium falciparum blood stages.

Unlabelled: Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans. This species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria population size as a mechanism to possibly explain these in vivo observations.

Metabolomics-Based Elucidation of Active Metabolic Pathways in Erythrocytes and HSC-Derived Reticulocytes.

A detailed analysis of the metabolic state of human-stem-cell-derived erythrocytes allowed us to characterize the existence of active metabolic pathways in younger reticulocytes and compare them to mature erythrocytes. Using high-resolution LC-MS-based untargeted metabolomics, we found that reticulocytes had a comparatively much richer repertoire of metabolites, which spanned a range of metabolite classes. An untargeted metabolomics analysis using stable-isotope-labeled glucose showed that only glycolysis and the pentose phosphate pathway actively contributed to the biosynthesis of metabolites in erythrocytes, and these pathways were upregulated in reticulocytes.