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  Regulation of protein translocation across the endoplasmic reticulum (ER) membrane


   Center for Human and Molecular Biology (ZHMB)

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  Prof k Römisch  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Proteins are transported through the ER membrane for biosynthetic protein import of secretory and transmembrane proteins and for misfolded protein export for degradation in the cytosol by proteasomes (ER-associated degradation, ERAD). Transport in both directions is mediated by the Sec61 channel, with different accessory proteins for the different directions of transport. Balanced protein import into and export from the ER are essential for cell survival, but so far little is known about regulation of Sec61 channel activity. We are currently investigating the role of phosphorylation on transport through the Sec61 channel, the mechanism of opening the channel from the lumenal side for export, and we are in the process of identifying export substrates whose transport is dependent on the interaction of the 19S regulatory particle of the proteasome with the Sec61 channel. We employ a mixture of protein biochemistry, yeast genetics, and cell-free assays to address these questions.

We are a small international lab working in a competitive area, so candidates need to be highly motivated and working to a high standard. The lab language is English, but acquisition of at least rudimentary German is desirable. The thesis can be written and defended in English. Candidates are expected to participate in teaching 2 practicals a year, and in co-supervising BSc and MSc students alongside their thesis work. PhD students are expected to finish within 3-4 years with at least one first-author publication.

Saarbrücken is the capital of the Saarland with 200,000 inhabitants. It is situated in the west of Germany on the French border, about equi-distant between Frankfurt and Paris (2h by train in either direction). The campus of the Saarland University with 17,000 students lies on the edge of town with good public transport and excellent sports facilities. Students here benefit from the rich cultural life with transnational film, theatre, and music festivals.

PhD students will be paid a standard German public service graduate student salary (TV-L E13, 50%). Applicants should have a BSc in Biochemistry, Biology, or Molecular Biology and should have completed a 2-year MSc programme in a similar area with above average grades. Experience with membrane protein purification, yeast genetics, or cell-free assays are a plus, but not mandatory.

Applications should be accompanied by a motivation letter and a CV detailing education and lab experience, including names and contact details of 2 referees. Potentially suitable candidates should be prepared to conduct a phone interview in English. Selected candidates will be invited to Saarbrücken for a more extensive interview.



Funding Notes

This post is funded by the Saarland University. It requires that the applicant has completed a 2-year MSc programme or equivalent , amounting to a total of at least 5 years of study at a university.

References

Römisch K (2017) A case for Sec61 channel involvement in ERAD. Trends Biochem Sci 42:171-179.
Kaiser ML & Römisch K (2015). Proteasome 19S RP binding to the Sec61 channel plays a key role in ERAD. PLoS ONE 10(2): e0117260.
Soromani C, Zeng N, Hollemeyer K, Heinzle E, Klein MC, Tretter T, Seaman MNJ, Römisch K (2012). N-acetylation and phosphorylation of Sec complex subunits in the ER membrane. BMC Cell Biol. 13:34.
Kalies KU, Alan S, Sergeyenko T, Kröger H, Römisch K (2005). The protein translocation channel binds proteasomes to the endoplasmic reticulum. EMBO J 24, 2284-93.