Elucidating mechanisms of extracellular vesicle-mediated cellular communication and stage conversion in malaria parasites. (360G-Wellcome-110166_Z_15_Z)

Malaria parasites cycle between an asexual proliferative and a sexual transmission stage during human infection. To enable efficient transmission to the mosquito vector parasites need to finely tune the balance between asexual reproduction and sexual development. We have shown that extracellular vesicles (EVs) can be transferred between parasite-infected red blood cells (iRBCs) and impact the rate of sexual stage activation, or sexual conversion rate [1]. At the same time these vesicles are inte rnalized by host endothelial cells and able to alter gene expression using host RNAi machinery [2]. These findings demonstrate that malaria parasites possess the capability to transfer such vesicles between iRBCs and other host cells, with various functional outcomes. Here we propose to define the mechanistic basis of vesicle-mediated cellular communication between iRBCs and its link to the regulation of sexual stage formation. Our specific questions are: i) how are EVs transferred between iRBCs ?; ii) What is the transcriptional signature in recipient iRBCs upon EV uptake?; iii) What are the active factors in EVs that alter recipient iRBC function, including activation of transmission stage formation?