Nutrient Uptake and Metabolism

During the pathogenic blood phase of the complex life cycle Plasmodium spends >99.9% of its life cycle inside host cells. This obligate intracellular niche in an extreme environment (i.e. terminally differentiated erythrocytes) requires metabolic adaptations, which until to date form the basis for antimalarial chemotherapy. This is exemplified by the drug chloroquine that inhibits non-toxic (hostderived) hemoglobin degradation in the parasite food vacuole. In this research area four projects examine the strict dependence of the parasite on external nutrient supply, ranging from ions to complex lipids.


Projects


Conserved and Lineage-specific Functions of Plasmodium Membrane Transport Proteins

KAI MATUSCHEWSKI (HUB) in partnership with Alexander Maier (ANU), Kiaran Kirk (ANU), and Giel van Dooren (ANU)

In this project a systematic experimental genetics analysis of candidate membrane transport proteins that are shared amongst apicomplexan parasites or unique to distinct Plasmodium species will identify and prioritize candidate drug targets. Lipids are often overlooked as some of the most important and versatile principal cellular components.


An integrated thermodynamic model of ion homeostasis in the malaria parasite

EDDA KLIPP (HUB) in partnership with KIARAN KIRK (ANU) and Adele Lehane (ANU)

The project entails obtaining quantitative biochemical and physiological data and incorporating these into a quantitative description of ion homeostasis in the intracellular malaria parasit.  The model will contribute to an understanding of the mechanism-of-action of ‘ion-disrupting’ antimalarials that are emerging as priority drug candidates in the malaria-medicine pipeline

Plasmodium falciparum lipid metabolism as a target for malaria intervention strategies

ALEXANDER MAIER (ANU) in partnership with Edda Klipp (HUB)

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.

 


Cyclic nucleotide-mediated ion homeostasis in the malaria parasite

NISHITH GUPTA (HUB) in partnership with Kiaran Kirk (ANU) and Alexander Maier (ANU)

The project will employ ultra-fast optogenetic regulation of ion channels to monitor the immediate cellular responses upon external stimuli and identify potential novel regulatory cascades that are unique to parasite stage conversion.