Each cell relies on thousands of internal biochemical reactions, carried out by around ten thousand different types of proteins. These cellular proteins, collectively known as the proteome, must be synthesised in precise quantities, undergo correct folding and be accurately localised within the cell. The process that ensures proper protein homeostasis in cells is referred to as “proteostasis.” It involves a sophisticated network of molecular machineries responsible for producing appropriately folded and assembled proteins and ensuring their timely availability at specific cellular sites.
The constituents of this proteostasis network include the ribosome, which synthesises 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 ageing 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, electron cryomicroscopy (cryo-EM), electron cryotomography (cryo-ET) and computational analysis. Current projects in the group 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.