Ilaria Fregno, a member of the Protein Folding and Quality Control laboratory headed by Prof. Maurizio Molinari at the IRB in Bellinzona, has been honored with the ETH Medal in recognition of her Outstanding Doctoral Thesis entitled “Anabolic and catabolic control of endoplasmic reticulum homeostasis”.
The prestigious ETH medal is awarded to less than 8% of the ETH students that successfully conclude their thesis. The thesis committee including Prof. ETH Benoît Kornmann, Prof. ETH Matthias Peter, Prof. ETH Anton Wutz and Prof. University of Groningen Fulvio Reggiori rated Ilaria’s experimental work, the written thesis and the oral presentation with the highest marks.
Ilaria’s study highlights the first example of receptor-mediated, lysosomal-regulated protein clearance from the endoplasmic reticulum (the protein factory in our cells). This pathway, which we named ER-to-lysosomes-associated degradation (ERLAD), clears from our cells misfolded proteins that form large aggregates or polymers that cannot be degraded by conventional pathways converging to the ubiquitin/proteasome degradation system. Ilaria’s studies focused on clearance from cells of ATZ polymers, whose intra-hepatic accumulation are the major cause of pediatric liver transplant linked to an hereditary disease.
Ilaria’s work, which was published in the EMBO Journal, paved the way for a collaborative project between our group and the groups of C. Settembre (TIGEM, Pozzuoli) and I. Dikic (University Hospital, Frankfurt am Main) that resulted in a second publication co-authored by Ilaria in the EMBO Journal that elucidated the intervention of ERLAD in clearance of misfolded, disease-causing forms of collagen (Ilaria’s publications).
The study by Ilaria is part of the investigation performed in our lab to elucidate dysfunctional mechanisms and pathways in rare diseases caused by expression of mutant gene products.