folded and assembled proteins and ensuring their timely availability at specific cellular sites.
The constituents of this proteostasis network include the ribosome, which synthesizes new proteins, chaperones that guide nascent proteins to fold and degradation factors that remove misfolded or damaged proteins. Perturbations in these processes can result in the accumulation of misfolded proteins that are detrimental to cellular function. Proteostasis dysregulation notably occurs during aging and is prevalent in a wide range of diseases including neurodegeneration, cancer and metabolic diseases.
The goal of our research is to understand how the proteostasis network is organised in different types of cells, how it changes during different physiologic conditions, and how it goes awry during stress and other pathologic states. We employ an advanced combination of biochemistry, cell biology, light microscopy, cryo-electron microscopy (cryo-EM), cryo-electron tomography (cryo-ET) and computational analysis. Current projects in the lab include the investigation of translational regulation in specific cellular conditions, analysis of proteostasis re-wiring during stress, as well as related method development aspects. We have a few project options available for a PhD student and the specific project will be refined to meet the student's interests, goals, and skills.
References
Fedry J, Silva J, Vanevic M, Fronik S, Mechulam Y, Schmitt E, des Georges A, Faller W, Förster F. Visualization of translation reorganization upon persistent collision stress in mammalian cells. Molecular Cell 2024, Mar 21;84(6):1078-1089.e4;
Gemmer M, Chaillet ML, van Loenhout J, Cuevas Arena R, Vismpas D, Gröllers-Mulderij M, Koh FA, Albanese P, Scheltema R, Howes SC, Kotecha A, Fedry J, Förster F. Molecular Snapshots of translation and protein translocation at the ER membrane. Nature 2023, 614 (7946), 160-167
Kucinska MK, Fedry J, Galli C, Morone D, Raimondi A, Solda T, Förster F, Molinari M. SEC62 and TMX4 control asymmetric autophagy of the nuclear envelope upon LINC complex disassembly. Nature Communications 2023, 14 (1), 3497
