Methylation in Motion: Decoding Cytoskeletal Dynamics in Apicomplexan Parasites

• Applicant: Dr. Elena Jimenez Ruiz
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Cell Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572426065

Apicomplexan parasites are a diverse group of single-celled organisms that include some important disease-causing pathogens, such as Plasmodium, which causes malaria, and Toxoplasma gondii, which causes toxoplasmosis. These parasites possess a unique structure called the apical complex, which aids them in invading, motility and active exit from the host cell. This structure houses many crucial proteins that play a key role in initiating and controlling the parasite's movement. Recently, we discovered a vital protein located at the very tip of the parasite, called CGP (conoid gliding protein), which is essential for initiating movement. Without CGP, the parasites cannot leave the host cell, making this protein a potential target for stopping the parasite from spreading. Over the past two years, I have independently continued this research and identified a new potential lysine methyltransferase that also localises to the pre-conoidal rings (PCRs) and interacts with CGP, named PCKMT (PreConoidal lysine (K) MethylTransferase). In recent times, methylation has been identified as a potential regulator of cytoskeletal dynamics, which could explain the impact on motility initiation in parasites lacking PCKMT. While the function of the methylase domain in PCKMT is still under investigation, PCKMT is important for recruiting the actin nucleator formin 1 (FRM1) to the PCRs, showing at least an indirect effect on actin dynamics. Previously, another methyltransferase, AKMT, was found to be necessary for recruiting the gliding-associated connector (GAC) to the conoid, indicating that methylation plays a critical role in the coordinated recruitment of proteins needed for movement initiation. The main objectives of this work are to understand the importance of this methylation process in regulating the cytoskeleton and motility of the parasite. Additionally, I aim to explore other similar enzymes that might also play a role in these dynamics. By focusing on these enzymes and their functions, we can gain valuable insights into how these parasites move and invade cells, potentially leading to new ways to stop them and treat the diseases they cause.

• DFG Programme: Research Grants