P. falciparum contains a unique organelle known as the apicoplast, a distinctive endosymbiont with its own genetic material.
During the parasite’s intraerythrocytic replication, the apicoplast develops from a little dot-like organelle in the nanometer range into an elongated branched structure of a few micrometers’ length.
We are interested to uncover the molecular machineries driving organelle development, replication and division throughout the life cycle.
Clp mediated Regulation
Most of the apicoplast proteins are encoded and regulated by the cell nucleus and it is unclear how the apicoplast controls its own proteome and biogenesis. In our research we discovered that a Clp (caseinolytic proteases) proteolytic system that resides within the apicoplast functions as a key regulator of organelle biology.
We hypothesize that the plastid is using Clp-mediated degradation as the main mechanism to control protein levels and the derived organellar functions. Using cellular assays such as microscopy, qRT-PCR and imaging-flow cytometry, and novel technologies including regulatable mutants, dominant-negative and new expression systems, we revealed the molecular interactions and the role of the Clp system as a master regulator of plastid proteome.
The apicoplast is an endosymbiont, which means that an ancient bacterium got incorporated into the cell and became an organelle. Throughout evolution, most of its genes got transferred to the cell nucleus, but some remained in a small chromosome inside the apicoplast. In this project, we try to understand why the apicoplast keeps its own genome and whether there are any hidden cellular functions within the apicoplast genes.
Developing Genetic Tool to Study Parasite’s Biology
Despite its clinical significance, P. falciparum remains a difficult-to-study non-model organism with a limited set of molecular tools, a challenge restricting our understanding of fundamental parasitic processes.
The impact of our research group stems from our ability and motivation to develop and apply advanced molecular-genetic and biochemical techniques for the study of unique parasitic phenomena. These include CRISPR/Cas9-mediated gene editing, various conditional-knockdown systems, marker-less genetic modifications, new expression systems and other novel technologies. With these advanced tools in hand, we ask questions that address fascinating biological problems in original ways.