New position2

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The HOLTHUIS LAB invites applications for

1 PhD student (f/m/d)

to work on

"Plasticity and physiological relevance of organellar lipid codes"

Project background

The identity and function of cellular organelles critically rely on information encoded in their lipid bilayers. Deciphering these “lipid codes” is a challenging task as they are based on the collective properties of the bulk lipids and because cells exploit a highly interconnected metabolic network to preserve an optimal lipid composition for each organelle. Sphingomyelin (SM) is a major component of cell membranes and a preferential binding partner of cholesterol. Bulk production of SM in the trans-Golgi is thought to provide a sink for cholesterol to help create a SM/sterol gradient along the secretory pathway. This gradient marks a fundamental transition in physical membrane properties that segregates early from late secretory organelles, allowing an adaptation from biogenic to barrier functions (Holthuis & Menon, 2014). We recently found that mutations in SM synthase SMS2 that block its export from the ER cause osteoporosis (Pekkinen et al., 2019), abolish the subcellular SM gradient and break transbilayer SM asymmetry (Sokoya et al., 2022). The central aim of this DFG-funded project is to unravel the functional implications of, and compensatory cellular responses to disease-induced imbalances in organellar lipids codes, with a main focus on aberrant distributions of the bulk lipid SM. Organellar lipidomics/proteomics will be combined with functional studies, fluorescent biosensors and live cell microscopy to address how a disease-linked accumulation of SM in the ER affects the organelle’s central role in stress signaling, membrane biogenesis and export of bone-critical cargo. Besides addressing fundamental concepts in lipid cell biology, these efforts should yield important insights into the pathobiochemistry of a severe bone disease. Refs: Holthuis & Menon, 2014, Nature 510, 48-57; Pekkinen et al., 2019, JCI Insight 4, e126180; Sokoya et al., 2022, eLife 11, e79278

Required qualifications

  • Completed degree (M.Sc.) in biology, biochemistry or biophysics
  • Solid background in assay development with expertise in live cell imaging, CRISPR/Cas9 technology and/or biomolecular mass spectrometry
  • 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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