During coevolution with the invertebrate and vertebrate hosts Plasmodium parasites adopted a wide range of tailored variations of a typical eukaryotic cell inventory, ranging from unique proteins and expression regulation, to specialized organelles and remodelling of the infected host cell. A better molecular understanding of these adaptations can aid in interpretations of malaria-related pathology and expose novel Achilles’ heels for malaria therapy. A prominent example of how distinct adaptations can be exploited includes Plasmodium susceptibility to a range of antibiotics that inhibit the essential function of the non-photosynthetic plastid organelle, termed apicoplast. In this research area six projects study the composition, function, and regulation of key features, including organelles, membrane structures and protein complexes, in Plasmodium parasites and in their host cells.
CHRISTIAN SCHMITZ-LINNEWEBER (HUB) in partnership with Giel van Dooren (ANU)
The project combines RNA biochemistry and experimental genetics towards a systematic analysis of Plasmodium organellar RNA metabolism. By organelle enrichment combined with proteomics and genome-wide profiling of signature binding sites the study will focus on a novel family of apicomplexan organellar RNA binding proteins and their functions in ribosome biogenesis and mRNA turnover.
SIMONE REBER (HUB) in partnership with Kevin Saliba (ANU)
The highly dynamic microtubule
cytoskeleton plays an essential role in the structural integrity of malarial
parasites. Consistent with its important role, microtubule-disruptive drugs
have great potential as anti-malarial agents. The current therapeutic options
of microtubule-disruptive drugs, however, are limited by their high toxicity to
mammalian cells. The aim of this PhD project is to characterize Plasmodium
tubulin biochemically and biophysically in order to improve its druggability
and to advance the potential of Plasmdium tubulin as anti-malarial.
MELANIE RUG (ANU) in partnership with Kai Matuschewski (HUB) and Alyssa Ingmundson (HUB)
Inside erythrocytes, Plasmodium refurbishes its host cell by inducing novel organelles, such as Maurer’s clefts, which are trafficking hubs for the export of virulence factors.In this project previously unrecognized proteins of the exported virulence complex will be analysed by state-of-the-art imaging tools, including correlative light and electron microscopy, in the human and murine model pathogens.
BENEDIKT BECKMANN (HUB) in partnership with Melanie Rug (ANU) and Brendan McMorran (ANU)
The first description of an RNA atlas of exosomes from P. falciparum -infected erythrocytes will be the focus of the project, which combines expertise in genome-wide pathogen RNA profiling, high-end imaging, and genetic characterization of selected targets.
ALYSSA INGMUNDSON (HUB) in partnership with Melanie Rug (ANU)
Host cell remodelling also occurs in Plasmodium-infected liver cells, and in the complementary project novel P. berghei proteins at the parasite-host interface that are shared between liver and blood stages will be studied by experimental genetic and biochemical techniques to characterize the molecular repertoire of parasite-induced host cell structures.
FRANK SEEBER (RKI) in partnership with Christina Spry (ANU), Kevin Saliba (ANU), and Alexander Maier (ANU)
The project will investigate a nexus between central metabolic pathways within the apicoplast and functionally dissect the vital roles of the redox regulator ferredoxin for distinct metabolic pathways that have already been validated as therapeutic targets.
Humboldt-Universität zu Berlin
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