Unravelling the anti-apoptotic tolerance pathway induced by OSIP108.

The recently identified plant peptide OSIP108 is reported to protect plants, yeast and mammalian cells against apoptosis-inducing stressors. In this project, I will unravel the signalling cascade that is induced by OSIP108 in yeast, in the presence and/or absence of copper as apoptosis-inducer. Subsequently, I will translate the obtained findings to the model plant, Arabidopsis thaliana. To this end, I will profoundly analyse our in-house generated RNA-sequencing data to find differentially expressed genes and regulatory RNAs to generate a transcriptional network. Additionally, I will perform cell penetration and protein interaction studies with OSIP108 in yeast to find its direct target(s). Alternatively, I will screen a yeast mutant library for altered sensitivity to the action of OSIP108, to find potential non-protein targets. Furthermore, I will examine the activity of a collection of OSIP108-derived peptides to (i) get insight into which amino acids are crucial for the anti-apoptotic activity of OSIP108 and (ii) find OSIP108-derived peptides with an improved activity. The identified OSIP108 targets will be validated with the best OSIP108- derivative in both yeast and A. thaliana (OSIP108’s original source). This project will shed light onto the fundamental cellular processes and anti-apoptotic tolerance pathways used by yeast and plant cells, thereby allowing drawing strong conclusions on the evolutionary conservation of such pathways between lower and higher eukaryotes.