NUTRIENT UPTAKE AND METABOLISM

Project A1 - 2nd Cohort

Conserved and Lineage-specific Functions of Plasmodium Membrane Transport Proteins

KAI MATUSCHEWSKI (HUB) in partnership with Alexander Maier (ANU)

An intracellular life style and population expansion strictly depends on efficient uptake of ions, nutrients, building blocks and membrane lipids. Mammalian Plasmodium parasites have very tight host species barriers and co-evolved with their respective hosts. Work in two Plasmodium parasite models, the murine malaria model P. berghei and P. falciparum blood cultures, combines phenotyping of the entire parasite life cycle and parasite/host cross-talk during infection with in-depth analysis of blood infection by the human human pathogen. These studies are expected to uncover druggable targets and generate virulence attenuated parasite lines for preclinical testing of malaria vaccine strategies.

Frederik Huppertz

Project A2 - 2nd Cohort

Lipids as targets for antimalarial drugs

ALEXANDER MAIER (ANU) in partnership with Kai Matuschewski (HUB), Edda Klipp (HUB), Elena Levashina (MPIIB)

Lipids – together with proteins and nucleid acids – are the major building blocks of cells. We have recently determined the lipid composition of the different life cycle stages of Plasmodium falciparum and Plasmodium berghei. Based on this data we will now determine key molecules that are important for lipid import and metabolism and explore their role and potential as drug targets. A bioinformatic overview obtained in silico will guide us to identify rate limiting steps in the lipid metabolism. These predictions will be verified using transgenic approaches using CRISPR/Cas9 and various tagging strategies. Our approaches will also determine the localization, function and importance of these enzymes and transporters for the survival of the malaria parasites.

TBD

Project A3 - 2nd Cohort

TBA

EDDA KLIPP (HUB) in partnership with Alexander Maier (ANU)

Lipids – together with proteins and nucleid acids – are the major building blocks of cells. We have recently determined the lipid composition of the different life cycle stages of Plasmodium falciparum and Plasmodium berghei. Based on this data we will now determine key molecules that are important for lipid import and metabolism and explore their role and potential as drug targets. A bioinformatic overview obtained in silico will guide us to identify rate limiting steps in the lipid metabolism. These predictions will be verified using transgenic approaches using CRISPR/Cas9 and various tagging strategies. Our approaches will also determine the localization, function and importance of these enzymes and transporters for the survival of the malaria parasites.

Maxim Karnetzki

Project A5 - 2nd Cohort

Role of host lipids in the establishment of the human malaria parasite in the mosquito 

ELENA LEVASHINA (MPI) in partnership with Alexander Maier (ANU) and Martin Blume (RKI)

Establishment of Plasmodium falciparum in the mosquito is essential for malaria transmission. However, the host and mosquito factors that regulate the first steps of this critical process are not well understood. P. falciparum transmission stages represent an interesting evolutionary model of plasticity as they require a rapid parasite adaptation to fundamentally different environments (e.g. temperature, metabolites, immune system). The biological mechanisms that underlie parasite plasticity that deals with changing environment, however, remain unknown.

Alexander Penning