New positions

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The HOLTHUIS LAB invites applications for

1 PhD student (f/m/d)

to work on

"Lipid-mediated repair of injured organelles and cells"

Project background

Damaged lysosomes threaten cell viability if their contents leak into the cytosol. ESCRT machinery can repair damaged lysosomes, which are particularly vulnerable to injuries. We recently uncovered an ESCRT-independent, sphingomyelin (SM)-based lysosomal repair pathway (Niekamp et al., 2022). Perturbations in lysosomal or plasma membrane integrity trigger a rapid, Ca2+-activated scrambling and cytosolic exposure of SM. Subsequent metabolic turnover of SM by neutral SMases on the cytosolic surface of injured lysosomes promotes their repair, also in ESCRT-compromised cells. Our findings indicate that Ca2+-activated scramblases, SM and neutral SMases are core components of a previously unrecognized membrane restoration pathway used by cells to reverse potentially lethal lysosomal damage. The central aim of this DFG-funded project is to elucidate the mechanistic principles by which SM scrambling and turnover drive membrane repair and whether a similar pathway functions at the plasma membrane to enhance survival of wounded cells. Toward this end, laser-wounding experiments are combined with functional assays, live cell imaging and 3D correlative electron microscopy. The project has significant clinical implications given that cancer cells critically rely on membrane repair mechanisms to resist attack by cytotoxic T cells (Ritter et al., 2022). Refs: Niekamp et al., 2022, Nature Communications 13, 1875; Ritter et al., 2022, Science 376, 377-382; Holthuis & Menon, 2014, Nature 510, 48-57.

Required qualifications

  • Completed degree (M.Sc.) in biology, biochemistry or biophysics
  • Solid background in assay development with expertise in membrane biochemistry, live cell imaging and/or CRISPR/Cas9 technology
  • Perseverance and the aspiration to work in a strongly interdisciplinary research environment
  • Very good commend of written and spoken English

We offer

  • An exciting and cutting-edge research project
  • Collegial cooperation in an interdisciplinary and international research team working on fundamental and disease-relevant aspects of lipid cell biology
  • State-of-the-art instrumental infrastructure in a cooperative working environment (CellNanOS; www.cellnanos.uni-osnabrueck.de)
  • Participation in the Collaborative Research Center SFB 1577 “Functional plasticity encoded in cellular membrane networks” and its structured doctoral training and support programs (irtg.uni-osnabrueck.de/application/sfb-1557.html)
  • UOS is located in the historical town of Osnabrück, the only German city situated in a national park

Conditions of employment

  • The application deadline is 1 March 2023. The position will be filled as soon as possible
  • The initial period of employment is 3 years. A 1-year extension is anticipated
  • Salary is at the E13/65% level according to the German TV-L scale
  • UOS is a family-friendly university and committed to helping working/studying parents balance their family and working lifes
  • UOS seeks to ensure equal opportunities for women and men and strives to correct any gender imbalance in its schools and departments
  • If two candidates are equally qualified, preference will be given to the candidate with disability status

How to apply

Applications including an informative letter of motivation, CV, publication list, certificates (BA/MA incl. Transcripts of Records) as well as the names and contact details of two academic referees should be sent as a single PDF-document by March 1st, 2023 to Prof. Dr. Joost Holthuis (holthuis@uos.de). Further information can be obtained from Prof. Dr. Joost Holthuis (holthuis@uos.de; Phone +49 541 969 7140).

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