Research Topic

Our focus is to improve our understanding of the underlying molecular mechanisms as well as the physiological changes that occur during cellular aging. Therefore, our group at BOKU-VIBT has established various techniques to screen for differentially expressed genes and proteins in early passage versus senescent human cells. One of the thereby identified novel genes was termed Senescence Evasion factor (SNEV) and selected for further characterization, since we observed that SNEV overexpression significantly delays entry of cells into replicative senescence. In the course of these studies we realized that the essential protein SNEV has multiple talents being involved in pre mRNA splicing, stress resistance, transport by interaction with the Exocyst complex, and finally ubiquitin-dependent protein degradation by directly interacting with the proteasome. Since neither of these pathways apart from stress resistance has been linked to replicative senescence yet, the aim of our ongoing research is to clarify how these pathways are mechanistically linked to each other.

Furthermore, we have identified several miRNAs that are differentially transcribed in young versus senescent cells and are functionally characterizing them in the context of cellular and organismal aging.

Finally, within an internal cooperation with Nicole Borth, who is also group-leader at BOKU-VIBT, we have combined our expertise in the miRNA field with their use as tools for engineering CHO cells, which are widely used as mammalian cell factories

Research Topic Johannes Grillari

Bioprocess-related targets for miRNA-mediated regulation of gene expression in mammalian cell factories. Generation of the pre-miRNA in the nucleus is

followed by pre-miRNA maturation in the cytoplasm. miRNA activation is accomplished after loading of the guide strand into RISC (RNA-induced silencing complex). Posttranscriptional

repression is mediated by cleavage or translational repression of target mRNAs. Thus miRNAs are believed to hold potential for altering cell-specific

characteristics in favor of an improved process performance. Abbreviation: IVC, integral of viable cells.