During invasion, Plasmodium parasites invaginate the host membrane and form a vacuolar niche called the Parasitophorous Vacuole (PV) which becomes the main interphase of host-pathogen interactions. Solute permeation across the PV membrane is mediated by a nutrient-permeable channel formed by a pore-forming protein called EXP2. In malaria parasites, EXP2 has been additionally functionalized for protein export by the AAA+ chaperone HSP101 and flange-like adaptor PTEX150 to form the Plasmodium Translocon of EXported proteins (PTEX). Recent work in our lab suggested that EXP2 traffics to the PV in a soluble state to avoid premature membrane insertion during vesicular trafficking. Therefore, my lab seeks to understand the mechanism used to insert EXP2 into the PV membrane in order to carry out PV transport functions. 

While nutrient exchange and protein export is mediated by EXP2/PTEX, recent work has shown that other proteins in the PV are involved in this process as well. One of these proteins is the rhoptry bulb protein RON3 which is secreted to the PV during invasion. Recent work has shown that interference with RON3 function leads to a block in nutrient exchange and protein export and our lab is interested in investigating the role of RON3 in these processes.

~10% of the genome is estimated to be exported to the RBC for host-cell subversion, however, only a fraction of these exported proteins have been validated to be exported. Moreover, our work has shown the presence of bona fide PEXEL motifs in non-exported proteins, hampering the predictive power of bioinformatic analyses in identifying PEXEL-containing exported proteins. We are interested in using the power of proximity labeling to identify the Plasmodium exportome using quantitative mass spectrometry.