Klaus Lingelbach Profile
	Research Focus:

The malaria parasite extensively modifies the cell biology of its host erythrocyte. Some of these modifications are required to support parasite survival within a nutritionally deprived host cell and others, such as cytoadhesive properties, contribute to the severe pathology of malaria. A common principle of all modifications is the appearance of parasite encoded proteins in specific locations within the infected cell or at its plasma membrane. This poses a cell biological enigma, as the differentiated erythrocyte is unable to synthesise lipids and proteins de novo, and it lacks an endogenous machinery to transport proteins to specific destinations. In addition, proteins secreted from the parasite need to be transported across the membrane of the parasitophorous vacuole, which separates the parasite from the host cell cytoplasm.

The research focus of the group includes (i) the identification of parasite proteins within the erythrocyte membrane which mediate uptake of nutrients from the intracellular milieu, (ii) the molecular mechanisms involved in trafficking of secretory parasite proteins within and beyond the confines of the parasite cell, and (iii) the identification and characterisation of the parasitophorous vacuolar proteome.

(i) We have provided experimental evidence that the uptake of nutrients requires parasite proteins which may act in concert with endogenous erythrocyte membrane proteins. (ii) We have established a permeabilised cell system which allows extraction of the erythrocyte cytosol, thus enabling us to study secretion of parasite proteins and their subsequent translocation across the parasitophorous vacuolar membrane in dependence of factors contained within the host cell cytosol. These studies employ both endogenous parasite proteins and reporter gene products. (iii) In our proteomic study we have identified more than 100 vacuolar proteins with a clear over-representation of proteases and chaperones, consistent with the expected functions of this compartment.

Standard tools in the laboratory include fractionation of infected erythrocytes and high throughput protein analyses.

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