Background and Goals
Germ cells - sperm and egg - are the products of a reproductive cell lineage, the germline. Since germ cells are the only cells producing a whole new individual in the next generation, the germline is often considered as the sole "immortal" cell lineage [1].
Using a simple genetic model, the nematode Caenorhabditis elegans (used to uncover important biological pathways such as apoptosis and RNAi), we and others demonstrated that conserved RNA-binding proteins (RBPs) play a critical role in maintaining germline identity [2]. One of these RBPs is LIN-41/TRIM71, a well-studied member of the TRMI-NHL protein family. Members of this family are critical regulators of the self-renewal versus differentiation decision, and are implicated in a range of disorders, from neurodegeneration to cancer [3]. In the absence of LIN-41-mediated mRNA regulation, germ cells abnormally differentiate into somatic cells forming the invertebrate equivalent of a human teratoma – a germ cell tumour in which some cells undergo haphazard differentiation into somatic cells [4]. How exactly LIN-41 represses mRNA targets remains unclear. In a functional proteomics screen, we identified candidate co-factors of LIN-41 and the goal of this project to examine their molecular functions in repressing specific mRNAs.
Methods
You will learn basic genetics, light and fluorescence microscopy, genome engineering, and a range of molecular biology methods.
Contact Person
- Rafal Ciosk; Ciosk Lab, Department of Biosciences, University of Oslo
References
- Cinalli, R.M., P. Rangan, and R. Lehmann, Germ cells are forever. Cell, 2008. 132(4): p. 559-62.
- Wright, J.E. and R. Ciosk, RNA-based regulation of pluripotency. Trends Genet, 2013. 29(2): p. 99-107.
- Tocchini, C. and R. Ciosk, TRIM-NHL proteins in development and disease. Semin Cell Dev Biol, 2015. 47-48: p. 52-9.
- Tocchini, C., et al., The TRIM-NHL protein LIN-41 controls the onset of developmental plasticity in Caenorhabditis elegans. PLoS Genet, 2014. 10(8): p. e1004533.