PhD project

PhD project

Mechanisms of protein quality control in health and disease

Supervisor: Pedro Carvalho

Accumulation of misfolded proteins and aberrant protein aggregates are hallmarks of a wide range of pathologies such as neurodegenerative diseases and cancer. Under normal conditions, these potentially toxic protein species are kept at low levels due to a variety of quality control mechanisms that detect and selectively promote their degradation. Our lab investigates these protein quality control processes with a particular focus on ER-associated degradation (ERAD), that looks after membrane and secreted proteins. The ERAD pathway is evolutionarily conserved and in mammals, targets thousands of proteins influencing a wide range of cellular processes, from lipid homeostasis and stress responses to cell signaling and communication.

We investigate the mechanisms of ERAD using multidisciplinary approaches both in human and yeast cells. We are using CRISPR-based genome-wide genetic screens and light microscopy experiments to identify and characterize molecular components involved in the degradation of disease-relevant toxic proteins. In parallel, we use biochemical and structural approaches to dissect mechanistically the various steps of the ERAD pathways. These strategies helped us in discovering ERAD mechanisms contributing to the homeostasis of the endoplasmic reticulum, the organization of the nuclear envelope and regulation of lipid metabolism. Although we focus primarily on fundamental aspects of protein quality control, our work will shed light on how these processes are disrupted in human disease and may ultimately contribute to better therapeutics.



Carvalho lab

Investigating the role the ER plays in protein degradation and organelle biogenesis.

Available PhD Projects

Over 30 groups work at the Dunn School to uncover the molecular and cellular mechanisms underlying disease. Discover which research groups are accepting students for our next round of applications.

About our PhD course

Doing a DPhil in Molecular Cell Biology in Health and Disease at the Dunn School is the best way to start your career.