The integrity of the genome transmitted to the next generation intrinsically relies on cells of the germ line. Processes that ensure germ cell development, genomic stability, and reproductive lifespan are essential for the long-term success of a species. We are interested in characterizing spermatogonial stem cell (SSC) populations that support fertility as well the regenerative capacity of the testis throughout adult life. In addition, we tackle fundamental questions regarding the mammalian male germ line and heredity from an RNA perspective. Specifically, our research explores the contribution of non-coding RNA (miRNA, piRNA and lncRNA) and RNA modification pathways within germ cell development as well as testicular homeostasis/regeneration. Our research objectives focus on the contribution of these emerging pathways on the underlying circuitry of self-renewal that underpins the SSC, as well as the coordination of the various cellular/differentiation processes of spermatogenesis.
The acquisition of both pluripotency and totipotency is associated with the deregulation of transposable elements – our goal is understand the mechanisms by which germ cells manage this formidable threat to the gametes, and thus transgenerational genome stability. Specifically, we explore transposon silencing in the germ line by the Piwi-interacting RNA (piRNA) pathway as well as epigenetic mechanisms.
- Comazzetto S, Di Giacomo M, Rasmussen KD, Much C, Azzi C, Perlas E, Morgan M, O'Carroll D. 2014. Oligoasthenoteratozoospermia and Infertility in Mice Deficient for miR-34b/c and miR-449 Loci. PLoS Genet. 10(10) doi:10.1371/journal.pgen.1004597.
- Di Giacomo M, Comazzetto S, Saini H, De Fazio S, Carrieri C, Morgan M, Vasiliauskaite L, Benes V, Enright AJ, O'Carroll D. 2013. Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis. Mol. Cell 50(4):601-08. doi:10.1016/j.molcel.2013.04.026.
- De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, Antony C, Moreira PN, Enright AJ, O'Carroll D. 2011. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 480(7376):259-63. doi:10.1038/nature10547.
- Yang JS, Maurin T, Robine N, Rasmussen KD, Jeffrey KL, Chandwani R, Papapetrou EP, Sadelain M, O'Carroll D, Lai EC. (2010) Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis. PNAS 107(34):15163-68. doi:10.1073/pnas.1006432107.
- Rasmussen KD, Simmini S, Abreu-Goodger C, Bartonicek N, Di Giacomo M, Bilbao-Cortes D, Horos R, Von Lindern M, Enright AJ, O'Carroll D. 2010. The miR-144/451 locus is required for erythroid homeostasis. J. Exp. Med. 207(7):1351-58. doi:10.1084/jem.20100458.
- Dr Anton Enright, EMBL European Bioinformatics Institute, Cambridge
- Dr Matthew Poy, Max Delbrueck Center for Molecular Medicine, Germany
- Dr Anne Schaefer, Mount Sinai School of Medicine, US
- Prof Alexander Tarakhovsky, The Rockefeller University, US
- Dr Philipp Selenko, Leibniz Institute of Molecular Pharmacology, Germany
- Dr Michaela Frye, WT / MRC Stem Cell Institute, UK