Deletion of genes related to the proteins secretion pathway in Aspergillus nidulans

Abstract

In eukaryotes, the unfolded protein response (UPR) up-regulates genes responsible for restoring homeostasis in the endoplasmic reticulum (ER) during the accumulation of unfolded or misfolded proteins. Conditions that overload the ER with these proteins include environmental stresses, changes in the ER redox status, and expression of heterologous proteins by biological systems such as filamentous fungi. The UPR genes were previously explored as a tool to increase protein secretion in heterologous expression systems, but the number of results is limited. Due to the complex regulatory network that governs the UPR response it may be difficult to choose target genes suitable for the improvement of the secretory pathway. In the fungi cells, the UPR regulates many genes that are involved in different processes, such as secretion pathway, glycosylation, ERAD (Endoplasmic-Reticulum-Associated Protein Degradation) and proteins folding. Therefore, the main goal of this project is to delete genes related to UPR, carefully selected from RNA seq data, in Aspergillus nidulans and observe the effect of these deletions on the secretion levels of heterologous proteins. The RNA seq data have been obtained from the growth of A. nidulans in the presence of chemicals that induce ER stress such as tunicamycin (Tm) and dithiothreitol (DTT). (AU)