Hybridization between plants with different ploidy often encounter post-zygotic reproductive barriers in the seed, which are mediated by transposon-derived small RNAs that disrupt genomic imprinting. Strikingly, this is highly reminiscent of hybrid dysgenesis in Drosophila, suggesting that plants and animals utilize similar small RNA guides to control transposon activity and dosage in hybrid genomes. EpiHYBRIDS aims to provide mechanistic insight into the origins and function of small RNAs responsible for hybrid seed collapse in Arabidopsis, by performing 1) large-scale small RNA depletion and 2) targeted epimutagenesis at imprinted loci with single-cell resolution. The overall goal of this project is to elucidate the epigenetic basis of genome dosage responses in interploidy crosses, but the results may provide valuable insight on additional small RNA-related phenotypes that are highly relevant for modern agriculture and food production, such as heterosis and apomixis.