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Mechanisms controlling organelle dynamics and quality control

  • Full or part time
    Prof P Carvalho
  • Application Deadline
    Friday, January 10, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Our lab is interested in membrane-bound organelles- how they form and acquire their distinctive proteome essential to carry their specialized functions. In particular, we focus on how organelle function is maintained through quality control processes. Our lab has been particular interested in a quality control process termed ERAD, which targets misfolded membrane proteins in the endoplasmic reticulum (ER). While some of the components of this process have been identified, the mechanisms by which diverse range of misfolded proteins are selected, ubiquitinated, extracted from the ER membrane and targeted for degradation by the proteasome remain elusive. To gain insight on the mechanisms of protein quality control our lab is taking multidisciplinary approaches. We are using CRISPR-based genome-wide genetic screens to delineate the molecular pathways involved in the degradation of disease-relevant misfolded proteins. In parallel, we use biochemical, proteomics and structural approaches to dissect mechanistically the multiple steps of ERAD. These studies will reveal the molecular basis of quality control processes by which misfolded and aggregation-prone proteins are handled by the cell both under normal and pathological situations. We are also interested in inter-organelle communications- which and how molecules are exchanged between organelles, which signals regulate those exchanges, etc. Although we do mostly basic research, we are interested how these processes are disrupted in human disease.

Funding Notes

4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£17,009 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

Olzmann JA, Carvalho P. (2018) Dynamics and functions of lipid droplets. Nat Rev Mol Cell Bio doi: 10.1038/s41580-018-0085-z
Wu H, Carvalho P, Voeltz GK (2018) Here, there, and everywhere: The importance of ER membrane contact sites. Science 361(6401)
Wang S, Idrissi FZ, Hermansson M, Grippa A, Ejsing CS, Carvalho P (2018). Seipin and the membrane-shaping protein Pex30 cooperate in organelle budding from the endoplasmic reticulum. Nat Commun.Jul 27;9(1):2939.
Ruggiano A, Mora G, Buxó L, Carvalho P. (2016) Spatial control of lipid droplet proteins by the ERAD ubiquitin ligase Doa10. EMBO J. Aug 1;35(15):1644-55.
Foresti O, Rodriguez-Vaello V, Funaya C, Carvalho P. (2014) Quality control of inner nuclear membrane proteins by the Asi complex. Science. 346(6210):751-5.
Ruggiano A*, Foresti O*, Carvalho P. (2014) ER-associated degradation: protein quality control and beyond. J Cell Biol 204(6):869-79.
Foresti O, Ruggiano A, Hannibal-Bach HK, Ejsing CS, Carvalho P. (2013) Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4. eLife Jul 23;2:e00953

How good is research at University of Oxford in Biological Sciences?

FTE Category A staff submitted: 223.80

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