Teodora Stojkovska
"I applied for this position because I am very interested in plant-pathogen interactions, and I find viroids especially fascinating since there is still so much to discover about them. I am also very happy to be a part of a doctoral network which gives me the chance to grow as a researcher, connect with others and build friendships along the way."
Teodora is ViroiDoc MSCA fellow in Spain (DC6) at the Valencia Polytechnic University (UPV) under supervision of Prof. Purificación Lisón.
Individual Research Projects (IRP):
Development of novel antiviroidal strategies: towards drug discovery
Viroids are small, non-coding plant pathogens that cause severe diseases in important crops, yet no effective control strategies are available. This project develops a cell-based system for assessing novel antiviroidal drugs, aiming to identify compounds that could form the basis of viroid-control solutions. Tobacco BY2 cells will be engineered to constitutively express Potato spindle tuber viroid (PSTVd) or Citrus exocortis viroid (CEVd), generating a robust model (BY2-Vd) to screen and characterize potential antiviroidal compounds. Using this platform, candidate molecules will be selected for efficacy testing from previous findings in our research group and related studies. Among them, salicylic acid plays a pivotal role in tomato basal resistance to CEVd, as demonstrated by NahG transgenic plants, which are unable to accumulate this hormone and consequently display extreme hypersusceptibility (López-Gresa et al., 2016). In addition, γ-aminobutyric acid (GABA), induced by benzothiadiazole (BTH) in tomato plants, enhances resistance to CEVd by reversing hypersusceptibility and activating defense genes (López Gresa et al., 2019). The TOR inhibitor AZD8055 mitigates PSTVd infection by restoring autophagy and strengthening tomato defenses (Silva-Valencia et al., 2024). Ethylene signaling has also been implicated, since reducing it can delay disease progression and alleviate ribosomal stress (Vázquez-Prol et al., 2020). Viroids also localize to translating polysomes and disrupt ribosome biogenesis, so agents that interfere with this interaction may relieve viroid-induced ribosome stress (Cottilli et al., 2019). To study the potential antiviroidal capacity of the compounds, their effects on BY2-Vd will be evaluated through viroid quantification by RT-qPCR and northern blotting, subcellular localization using fluorescence microscopy, profiling of small RNA populations by sRNA-seq, and expression of host marker genes (PR1, NAC82). Promising compounds will be subsequently tested in planta, using tomato plants infected with PSTVd or CEVd and Nicotiana benthamiana infected with PSTVd. These studies will further be extended to Chrysanthemum chlorotic mottle viroid (CChMVd), a member of the Avsunviroidae family. Overall, our work provides a framework for identifying antiviroidal drugs and lays the groundwork for practical solutions against viroid diseases.
T. Stojkovska, F. Di Serio (CNR), K. Kalantidis (UoC), P. Lisón (UPV)
The text above was submitted as poster abstract for the Viroids2025 conference in Bari, Italy.
Project presentation