RNA mediated regulation of reprogramming
The nematode Caenorhabditis elegans is a powerful experimental model, which yielded many key discoveries like apoptosis or RNAi. In this project, we will use C. elegans and mammalian cells to understand specific events of post-transcriptional gene regulation involved in regulation of reprogramming.
Cellular reprogramming is a process opposite of cellular differentiation, wherein a specialized cell is converted into a pluripotent cell that can give rise to different types of cells. Understanding the roadmaps to pluripotency has immense clinical importance. During animal development, a complete reprogramming into pluripotency is rare, being restricted to the process of oocyte to embryo transition (OET). During OET, a fertilized oocyte develops into a pluripotent embryo, which has the potential to give rise to an entire new individual. Recently several RNA binding proteins like GLD-1 and LIN-41 have been identified as cytoplasmic roadblocks to pluripotency by regulating post-transcriptional gene expression. LIN-41, a TRIM-NHL family protein that directly binds to RNA via its NHL domain. Human LIN41 (TRIM71) has also been implicated in cellular plasticity, facilitating the reprogramming of differentiated cells into pluripotent cells.
In the proposed masters project the student will work towards dissecting the different modes of RNA binding by LIN-41 and uncover the associated mechanisms underlying LIN-41 mediated RNA regulation. From IP-mass spec, we have indentified a number of proteins associated with the LIN-41 complex. Using mRNA reporters with tissue specific expression in the C. elegans, we will determine the function of partner proteins in LIN-41 mediated RNA regulation. Additionally, we will perfrom immunoprecipitation (IP) experiments to disssect the interaction between LIN-41 and partner proteins and identify the domains involved in this interaction. As LIN-41 medaited RNA regualtion is conserved in higher oraganisms, we will also use mammalian cell culture system to dissect the molecular circuitary of LIN-41 medaited RNA regulation by transiently expressing the different compoents in HEK-293 cells.
The laboratory and contact
The Ciosk laboratory <https://www.mn.uio.no/ibv/english/people/aca/rafalc/>, is located at the Department of Biosciences, Section of Molecular Biology and Biochemistry. Interested students please contact Rafal Ciosk as soon as possible.
Office: Kristine Bonnevies hus, Blindernvn. 31, Room. 2110