Research Area: Parasite Genetics and Adaptations
Leading PI: Frank Seeber
Dissecting the distinct metabolic roles of the ferredoxin redox system
The apicoplast is an essential plastid-like organelle of Plasmodium spp. and Toxoplasma gondii parasites. Its ferredoxin (Fd) redox system plays a central metabolic role as electron donor to enzymes via protein-protein interactions (PPI). The aims of the project is to study Fd’s PPIs to dissect its metabolic roles in the apicoplast and to elucidate in Plasmodium the role of reported Fd mutations in artemisinin resistance. These will be approached by genetic screens in E. coli for PPI inhibitors (i.e. cyclic peptide ‘dissociators’) and their subsequent biophysical and in situ validation in the parasite on Fd’s function. These studies will be complemented with Fd gene knock-out in Plasmodium and assessment of artemisinin resistance with complemented mutants.
We are looking for:
Potential candidates should ideally have a profound theoretical as well as experimental background in molecular techniques like DNA cloning, library constructions, cell transfections, protein analysis techniques and/or fluorescent microscopy. A substantial interest in biochemical questions paired with a strong ambition for innovative ideas are a perfect match to make this interesting project a success.
Research Area: Nutrient Uptake and Metabolism
Leading PI: Alexander Maier
Plasmodium falciparum lipid metabolism as a target for malaria intervention strategies
The project will combine state-of-the-art lipidomics analyses of synchronized and selected parasite stages with mathematical modelling of lipid fluxes in order to select key enzymes and transporters that can be validated experimentally. An integrated mathematical model for ion and cell volume homeostasis in the malaria parasite-infected human erythrocyte remains elusive.
Research Area: Parasite Genetics and Adaptations
Leading PI: Melanie Rug
Characterisation of the virulence complex of the malaria parasite
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.
Research Area: Immune Responses
Leading PI: Brendan McMorran
Identification and analysis of platelet polymorphisms associated with malaria susceptibility
In the project the seminal finding that platelets are instrumental in killing of Plasmodium-infected erythrocytes permits the functional testing of whether candidate polymorphisms in platelet-associated genes cause malaria susceptibility. This study encompasses genotyping in patient cohorts and cell culture assays as proxy for platelet functions in infected patients. Sporozoite-based immunization strategies are presently one of the most promising roads towards an efficacious malaria vaccine.
Leading PI: Ian Cockburn
Novel adjuvants for pre-erythrocytic stage vaccines
The project will combine self-devised immunoglobulin transgenic mice and lentiviral knockdown libraries for the evidence-based development of adjuvants that permit superior B cell responses against inactivated sporozoites, which are notoriously weak in eliciting lasting immunity. Hence, this project could remove a major roadblock in development of whole sporozoite vaccines for use in endemic countries.
Research Area: Host Genetics and Responses
Leading PI: Gaétan Burgio
Unravelling the host response to malaria infection
The project will validate novel host resistance candidates by reverse genetics and analyse the effects of host genotypes on the response to artemisinin treatment and on parasite development and disease progression in a murine infection model.
Leading PI: Kevin Saliba
Familial flavin deficient erythrocytes and malaria susceptibility
The project originates from the identification of a local focus of familial flavin deficiency that is likely linked to previous malaria endemicity. Employing biochemical assays, the prevalence of flavin-deficient erythrocytes in SubSaharan Africa will be explored to identify genetic markers and correlate flavin deficiency with malaria incidence and disease progression.
Leading PI: Simon Foote
Screening for inhibitors of parasite growth using circular peptides and previously identified host targets
The concept of host directed therapy of Plasmodium blood infection will be experimentally tested for the first time in the project. Employing a circular peptide library, inhibitors of interactions between erythrocyte cytoskeletal proteins will be selected and further characterized in P. falciparum cell culture assays. A range of additional targets that were identified from in silico and forward genetics screens will be included in the screening pipeline.
The Australian National University
Research School of Biology
134 Linnaeus Way
Canberra - Acton ACT 2601
Humboldt-Universität zu Berlin
Unter den Linden 6