In prior work, we showed that RNAi has a major role in regulating spermatogenesis, via a special class of rapidly evolving siRNA substrates termed hpRNAs. In ongoing unpublished work, we characterized the genomics of hpRNAs across the Drosophilids, which we believe unlock a map of genomic conflicts controlled by RNAi pathway. We also knocked out the RNAi pathway in a non-model fruitfly and revealed surprising male-specific phenotypes much more overt than in D. melanogaster, reflecting derepression of emergent meiotic drive systems that do not exist in the flagship fruitfly.
We know little of the profound activities of recently-emerged selfish genes that are controlled by hpRNAs and how they affect gametogenesis, and how such factors come to be recognized and extinguished by small RNA pathways. These topics are central to understanding the biology of RNAi and mechanisms of speciation. To elucidate these questions, the ideal postdoctoral candidate will have familiarity with gonadal biology, Drosophila genetics and genome engineering, and be interested to integrate these techniques with molecular and genomewide approaches in a multidisciplinary lab environment. As well, this project is relevant to other ongoing interests in the group that examine the testis with respect to rapidly-evolving miRNAs and protein-coding genes, and post-transcriptional regulatory pathways, that all seem to reflect the unique gene expression environment of this tissue.
■ References on hpRNA pathway
Okamura, K., W.-J. Chung, J. G. Ruby, H. Guo, D. P. Bartel and E. C. Lai (2008). The Drosophila hairpin RNA pathway generates endogenous siRNAs. Nature 453: 803-806.
Wen, J., H. Duan, F. Bejarano, K. Okamura, L. Fabian, J. A. Brill, D. Bortolamiol-Becet, R. Martin, J. G. Ruby and E. C. Lai (2015). Adaptive regulation of testis gene expression and control of male fertility by the Drosophila hairpin RNA pathway. Molecular Cell 57: 165-78.
Lin, C.-J., F. Hu, R. Dubruille, J. Wen, P. Smibert, B. Loppin and E. C. Lai (2017). The hpRNA/RNAi pathway resolves intragenomic conflict to preserve balanced sex ratio. In preparation.
■ Related literature on testis gene regulation
Mohammed, J., D. Bortolamiol-Becet, A. S. Flynt, I. Gronau, A. Siepel and E. C. Lai (2014). Adaptive evolution of testis-specific, recently-evolved, clustered miRNAs in Drosophila. RNA 20: 1195-1209.
Lin, C.-J., J. Wen, F. Bejarano, F. Hu, D. Bortolamiol-Becet, L. Kan, P. Sanfilippo, S. Kondo and E. C. Lai (2017). Characterization of a TUTase/RNase complex required for Drosophila gametogenesis. RNA 23: 284-296.
Kondo S., J. Vedanayagam, J. Mohammed, S. Eizadshenass, N. Pang, L. Kan, R. Aradhya, A. Siepel, J. Steinhauer and E. C. Lai (2017). Young genes are rarely essential but have preferential impacts on spermatogenesis. Genes and Development, in revision.
Sanfilippo, P., J. Wen, S. Shenker and E. C. Lai (2017). Landscape and evolution of tissue-specific alternative polyadenylation across Drosophila species. Under review.