PROJECT SUMMARY
Biomolecular condensates are dynamic, membrane-less organelles formed within cells, and both host
cells and viruses encode proteins that can assemble into these structures, facilitating essential cellular processes
and viral replication. My laboratory uses model plant viruses like Pea enation mosaic virus 2 (PEMV2) and Turnip
crinkle virus (TCV) to understand better virus-host interactions that take place in biomolecular condensates. Over
the next five years, our objectives encompass several key aspects. Initially, we will investigate the specific
mechanisms through which viral condensates, particularly focusing on p26 from PEMV2, disrupt cellular
translation. Additionally, we will utilize nanopore sequencing to explore their potential role in interfering with
fibrillarin-mediated 2'-O-methylation of ribosomal RNAs. We will use transcriptome-wide methodologies (e.g.,
TRAP-seq) to comprehensively investigate the impact of viral condensates on the translatome during infection
and test the hypothesis that viral condensates promote translational repression of antiviral transcripts while
enhancing translation of pro-viral transcripts. Using a similar approach, we will investigate whether viral
condensates function as a molecular switch, repressing the translation of viral transcripts to favor late stages of
the virus replication cycle, such as packaging and release.
Next, we will shift our efforts to understanding how nuclear condensates formed by the coat protein (CP)
of TCV inhibit RNA interference (RNAi), potentially via the sequestration of siRNA precursors. We will also
investigate whether CP condensates interfere with the epigenetic regulation of siRNAs to alter their stability and
host gene expression. Our research program's overarching vision is to employ model systems to understand
better how viral biomolecular condensates disrupt cellular homeostasis, ultimately promoting virus fitness. This
research addresses a critical knowledge gap by investigating the impact of viral condensates on host cell
function, an area that has received limited attention compared to the extensive research on their effects on virus
replication. Our research will also yield novel virus-host interactions with potential applicability across diverse
RNA virus families, potentially serving as a foundation for developing innovative therapeutics. Finally, my
research program will develop undergraduate and Ph.D. students from diverse backgrounds. These students
can assume lead authorship roles in future manuscripts and engage in career development initiatives, including
international conferences.