The MAPK-organizer protein 1 (MORG1), plays a scaffolding function for number of molecules involved in the MAPK cascade. Furthermore, it was found that it binds to prolyl-hydroxylase -3 (PHD3) isoform. Our studies revealed that reduction of MORG1 expression leads to reduced PHD3 activity and increased HIFs transcriptional activation. While MORG1 KO mice are embryonic lethal, the reduction of MORG1 expression in MORG1+/- mice was associated with an increased stabilization of the HIFs in animal models of Type 1 and 2 DM, as well as in ischemia-reperfusion model, compared with equally treated wild type MORG1 animals. This resulted in a decreased apoptosis, reduced inflammation and improved renal function. Furthermore, we observed that a reduced expression of MORG1 has a renoprotective effect in animal models of short-time systemic hypoxia and endotoxemia. Therefore, understanding the molecular mechanisms of the transcriptional regulation of MORG1 expression and the protein complexes in which MORG1 is involved in renal cells could be of therapeutic interest.  

During the summer school experimental week we will study the effects of different factors, as increased glucose levels, TGF-beta, hypoxia or 3,4 DHB (PHDs inhibitor) on the MORG1 expression in HEK 293 cells. Using as a tool CRISPR/CAS9 system, we generated HEK 293 cells, expressing human MORG1-fusion to Luciferase gene in order to monitor the Luciferase activity as a reporter for the MORG1-protein expression. Furthermore, the MORG1 expression will be assayed by real – time PCR. The cellular distribution of MORG1-protein will be visualized by immunofluorescent staining in HEK293 cells and/ or murine renal cells.