Gene regulation during cellular stress and its role in disease and resistance to therapy
Cells are exposed to various environmental stresses and have evolved dedicated genetic programs to survive and proliferate despite the challenges. Cellular stress response pathways have emerged as drivers of human diseases including cancer, diabetes and neurodegeneration. We are using multi-omics analyses to gain insight into post-transcriptional gene regulation during stress.
The Unfolded Protein Response (UPR)
The endoplasmic reticulum (ER) is the main cellular compartment in protein folding and maturation with about one third of the proteome being synthesized at the ER. Perturbation of ER proteostasis and accumulation of unfolded proteins trigger an adaptive signal transduction pathway, the Unfolded Protein Response (UPR), that adjusts gene expression to restore cellular homeostasis.
To gain a better understanding of the UPR we have generated comprehensive datasets of the UPR in cellular models using a multi-omics approach. This endeavor was pursued in a collaborative effort with the labs of R. Ahrends (ISAS Dortmund), B. Tews (DKFZ Heidelberg), G. Tödt (EMBL Heidelberg), and C. Knobbe-Thomsen (Heinrich-Heine University Düsseldorf) in the framework of the SUPR-G consortium (Systems biology of the Unfolded Protein Response in Glioma) which was funded by the German Federal Ministry of Education and Research (BMBF) in the framework of the e:Med initiative.