Kemri-Wellcome Trust Research Programme: Identifying new intervention and diagnostic targets through characterisation and functional analysis of the P. falciparum extracellular secretome.

I plan to describe the extracellular secretome of P. falciparum clinical isolates; the causative agent of the most severe form of malaria. The secretome is essential for interactions within the pathogen population and with the host. Analysing the secretome of pathogens may provide new targets for vaccines, drugs, diagnostics and biomarkers for understanding mechanisms of virulence of pathogens. The secretome of P. falciparum has not been comprehensively described. Only one study has attempted t o characterise it proteomically using a single laboratory isolate. Furthermore, the secretome of clinical isolates may well be significantly different from laboratory isolates, just as the secretome of primary hepatocytes was shown to be different in quantity and composition from that of hepatocytes derived cell lines. Analysis of the P. falciparum secretome based on a single laboratory line is therefore unlikely to capture the full spectrum of the composition. I therefore, propose to comprehen sively describe the proteomic and genetic composition of both the vesicular-packaged and soluble forms of P. falciparum secretome using short-term cultured clinical isolates with available full genome sequences. I will also investigate whether P. falciparum secreted proteins play a role in immunity taking advantage of the unique resources available at KWTRP, Kilifi.

Programme: International Training Fellowship

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