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O'Carroll Group

Non-coding RNA function and RNA modification in germ/stem cell biology

 

The O’Carroll group studies mouse blood cell formation, embryology and germ cell development using state-of-the-art genetic strategies and high-throughput sequencing approaches.

Previous and current research

The goal of my laboratory is to explore the contribution of non-coding RNA as well as RNA modification pathways to tissue development and homeostasis. We have garnered much experimental expertise in both haematopoiesis and the germline. Within the laboratory, an emphasis (non-exclusive) is now placed on studying the immortal lineage. The integrity of the genome transmitted to the next generation intrinsically relies on cells of the germline. Processes that ensure germ cell development, genomic stability, and reproductive lifespan are essential for the long-term success of a species. We tackle fundamental questions regarding the mammalian male germline and heredity from an RNA perspective. Specifically, our research explores the contribution of non-coding RNA (miRNA, piRNA and lncRNA) as well as RNA modification pathways within germ cell development as well as testicular homeostasis and regeneration.

The precise identity of the spermatogonial stem cell (SSC) in vivo that supports spermatogenesis throughout life remains unknown. Capitalising on the fact that SSC maintenance is dependent upon several RNA-binding proteins, we hope that investigation into these pathways may reveal the identity of this stem cell in vivo. The maturation of RNA sequencing techniques, in combination with refined genetic approaches, now renders the identification and functional evaluation of noncoding RNAs and RNA modifications in vivo within the realm of experimental feasibility. 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 the germ cells manage this formidable threat to gametes, and thus transgenerational genome stability. Specifically, transposon silencing in the germline by the Piwi-interacting RNA (piRNA) pathway as well as epigenetic mechanisms will be extended upon from our previous findings.

Future projects and goals

  • The identification and characterisation of the spermatogonial stem cell populations.
  • Dissection of the pathways required for spermatogonial stem cell selfrenewal and testicular regeneration.
  • Post-transcriptional RNA modification in germ cell and hematopoietic development.
  • Long non-coding RNA function in spermatogenesis.
  • Establishment and maintenance of epigenetic transposon silencing in the male germ line.