(ERAD), which monitors the quality of membrane and secreted proteins.
ERAD is an evolutionarily conserved pathway that regulates the turnover of thousands of proteins in mammalian cells, influencing diverse cellular processes including lipid metabolism, stress responses, cell signaling, and intercellular communication. Defects in ERAD have been linked to a wide range of human diseases, highlighting its central role in cellular homeostasis.
We study ERAD using multidisciplinary approaches in both human and yeast model systems. By combining CRISPR-based genome-wide genetic screens, advanced fluorescence microscopy, biochemistry, and structural biology, we seek to uncover the molecular mechanisms that control the recognition and degradation of disease-relevant proteins. Our work has revealed previously unrecognized roles for ERAD in maintaining endoplasmic reticulum homeostasis, organizing the nuclear envelope, and regulating lipid metabolism.
Our research is driven by fundamental biological questions while maintaining strong relevance to human health. Students joining the lab will have the opportunity to work at the interface of cell biology, genetics, biochemistry, and structural biology, contributing to discoveries that may ultimately inform new therapeutic strategies for protein-misfolding diseases.
Funding Notes
4 Year DPhil Prize Studentships cover full University fees, a tax free enhanced stipend of ~£24,305 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.
References
Bryant OJ, Sergejevs N, Giacomo F, Robson-Tull J, Deme JC, Forrest LR, Carvalho P, Lea SM. (2026) Dimeric architecture and membrane thinning govern substrate recognition by human signal peptide peptidase. Res Sq [Preprint] doi: 10.21203/rs.3.rs-9372626/v1.
- Sergejevs N, Carvalho P. (2025) Mechanisms of transmembrane domain recognition during ER quality control. Curr. Opin. Cell Biol.
- Ji Z, Siu WS, Duenas ME, Müller L, Trost M, Carvalho P. (2025) Suppression of TGF-β/SMAD signaling by an inner nuclear membrane phosphatase complex. Nat Commun. Apr 11;16(1):3474
- Krshnan L, Siu WS, Van de Weijer M, Hayward D, Guerrero EN, Gruneberg U, Carvalho P. (2022) Regulated degradation of the inner nuclear membrane protein SUN2 maintains nuclear envelope architecture and function. eLife 10.7554/eLife.81573
- Klug Y, Deme J, Corey R, Renne M, Stansfeld P, Lea S, Carvalho P. (2021) Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex. Nat Commun.
- van de Weijer M, Krshnan L, Liberatori S, Guerrero EN, Robson-Tull J, Hahn L, Lebbink RJ, Wiertz E, Fischer R, Ebner D, Carvalho P (2020). Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex. Mol Cell.
- Natarajan N, Foresti O, Wendrich K, Stein A, Carvalho P. (2020) Quality Control of Protein Complex Assembly by a Transmembrane Recognition Factor. Mol Cell.
- Ruggiano A, Mora G, Buxó L, Carvalho P. (2016) Spatial control of lipid droplet proteins by the ERAD ubiquitin ligase Doa10. EMBO J.
- Foresti O, Rodriguez-Vaello V, Funaya C, Carvalho P. (2014) Quality control of inner nuclear membrane proteins by the Asi complex. Science.
