Dissecting the molecular mechanisms of miRNA-binding Argonautes in spermatogenesis: shedding light on unexplored regulators of paternal fertility

• Applicant: Dr. Volker Nitschko
• Subject Area: Developmental Biology ; Biochemistry ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 521962024

The life of an organism is dependent on tight regulation of many inter-connected processes; from the whole organism down to the level of individual molecules within cells. If one or more of these regulatory processes malfunctions, this can severely affect the health and development of the organism. One important type of regulatory pathway is RNA interference (RNAi). RNAi pathways are composed of two core parts, a short RNA and a protein called Argonaute (AGO). The RNA acts as an “postal code” that guides the AGO protein to the specific target molecules (larger RNAs that ultimately make proteins). There are multiple RNAi pathways, including the microRNA (miRNA) pathway, which gets its name from the small RNA component. The miRNA pathway was first discovered in the tiny roundworm Caenorhabditis elegans, which is our model organism of choice for this study. The miRNA pathway is present in organisms ranging from sponges to plants and humans, playing important roles in cellular and organismal development, inheritance, and fertility. Our lab recently discovered that only two out of the 19 AGOs present in C. elegans are associated with miRNAs and expressed during spermatogenesis. Most studies on miRNA regulation have explored their functions in embryogenesis and oogenesis, thus the functions of miRNAs in spermatogenesis and their effects on paternal fertility are poorly understood. C. elegans shares over half the proteins found in human spermatogenesis, and a large portion of the miRNAs. We will use it as a model because it is easy to culture in the lab, and we have a multitude of scientific tools at our disposal. The combination of these features makes it the optimal organism for our study. Our study will inform further foundational studies on the regulation of spermatogenesis via RNAi, and in particular the miRNA pathway, in more complex organisms like humans. This has the potential to uncover novel fertility treatments along with non-hormonal contraception options.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professorin Dr. Julie M. Claycomb