Proteostasis in the early secretory compartment as a pathogenetic mechanism and therapeutic target

Like big cities, our cells are divided in specialized districts. Proteins must hence reach the proper district to perform their jobs. Recently, molecular and cell biologists have unravelled some of the mechanisms regulating intracellular traffic, learning how proteins normally reach their destination. This had an enormous impact on genetic diseases, many of which arise because the gene product, a protein, cannot reach the district where it is needed. In several genetic diseases (e.g. Endoplasmic Reticulum Storage Disorders), the mutated proteins accumulate in cells owing to altered transport and cause gain of a toxic function.Our project aims at understanding how cells manage to produce, sort and release impressive quantities of proteins of the highest quality, discarding the bad ones. Only if we comprehend in detail the underlying mechanisms, we'll be able to fully understand the molecular pathogenesis of different genetic diseases, to design strategies to restore proper protein delivery, and to relieve the toxicity due to abnormal protein accumulation in -traffic- diseases. By defining key regulatory mechanisms governing quality and efficiency of secretion, our studies may contribute to improve production of recombinant proteins for cell and replacement therapy, which are used in diverse genetic disorders.