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University of Basel

PhD Position on the Structure and Assembly Mechanism of the Ninjurin-1 Membrane Perforation Pore in Executing Cell Death (P2102)

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The Swiss Nanoscience Institute (SNI) at the University of Basel invites highly motivated scientists to apply for the SNI PhD program in Nanoscience.
The rupture of the eukaryotic plasma membrane mediated by the membrane protein ninjurin-1 is the defining end point of multiple different types of cell death. We aim at deciphering the mechanisms of ninjurin-1 in assembling membrane rupturing pores by a unique combination of structural biology methods, nanotechnological approaches, and super-resolution light microscopy.

Background: Eukaryotic cells possess remarkable control mechanisms to retain functionality during their life cycle and to ensure their proper removal in the multicellular context [1,2]. Among these mechanisms are multiple forms of cell death, most of which end with the rupture of the plasma cell membrane. So far, rupture of this membrane was generally thought to be a consequence of osmotic pressure, caused by uncontrolled influx of water. It was recently discovered that plasma membrane rupture is an active process, mediated by the protein ninjurin-1 [3]. Ninjurin-1 is a ubiquitously expressed, 16-kDa plasma membrane protein, and conserved from fruit fly to man [4] Understanding this process at atomic level will be crucial for therapeutic intervention.
Goal of this thesis: We want to determine the structure of the ninjurin-1 membrane inserted pore at atomic level and unravel its insertion mechanism in the cellular context. We aim at the atomic resolution structure of the ninjurin-1 pores by single-particle cryo-electron microscopy [5,6]. In addition, we will characterize the ninjurin-1 system by NMR spectroscopy [6]. In parallel, we will monitor ninjurin-1 oligomeric assembly and pore formation by AFM and TEM [7–10]. Time-lapse multiparametric AFM will allow us to image the pore formation process at a resolution of ≈1-2 nm and to simultaneously map how ninjurin-1 insertion and assembly alters the mechanical properties of the target membrane. Along a third line of research, we will also study the pore assembly in living cells by MinFlux microscopy, which allows an isotropic resolution of 1-5 nm of fluorophores in 3D [11,12].

This project follows a long standing and highly fruitful collaboration between the Hiller and Müller labs, combining their complementary expertise in biophysics and structural biology [7,10,13]. With the relocation of the D-BSSE to the Schellenmätteli campus in mid 2022, the two labs will be next neighbors. The student will be embedded in both groups and have full infrastructure access at both departments.

[1] Broz P et al. Nat Rev Immunol 20, 143–157 (2020), [2] Broz P et al. Nat Rev Immunol 16, 407–420 (2016), [3] Kayagaki N et al. Nature 591, 131–136 (2021), [4] Araki T et al. Neuron 17, 353–361 (1996), [5] Kaur H et al. Nature 593, 125–129 (2021), [6] Sborgi L et al. Proc Natl Acad Sci USA 112, 13237–13242 (2015), [7] Sborgi L et al. EMBO J 35, 1766–1778 (2016), [8] Dufrêne Y et al. Nat Methods 10, 847–854 (2013), [9] Dufrêne Y et al. Nat Nanotech 12, 295–307 (2017), [10] Mulvihill E et al. EMBO J 37, e98321 (2018), [11] Gwosch KC et al. Nat Methods 17, 217–224 (2020), [12] Schmidt R et al. Nat Commun 12, 1478 (2021), [13] Thoma J et al. Nat Struct Mol Biol 22, 795–802 (2015)
Candidates are required to have a MS degree in natural sciences, preferably with a solid background in the topics described above, as well as good English language skills. We seek a scientifically ambitious individual who enjoys working in an interdisciplinary and collaborative environment on a highly competitive subject.
  • Excellent scientific and social environment
  • Very competitive employment conditions
  • Membership in a very supportive and recognised community

The successful candidate will join an attractive interdisciplinary programme together with the ~30 currently supported scientists. The SNI covers a wide variety of topics, including cutting edge quantum physics and chemistry, material science, nanotechnology, biochemistry, cell biology, or medical research.
Application / Contact

More information and the online application platform can be found at www.phd.nanoscience.ch. For questions please contact the head of the SNI PhD programme, Dr. Andreas Baumgartner (andreas.baumgartner@unibas.ch), or directly the respective project leaders. The complete application has to be submitted before 31 December 2021. Please note that the decision to fill a given vacancy can be taken at any time from now.

Job details

Title
PhD Position on the Structure and Assembly Mechanism of the Ninjurin-1 Membrane Perforation Pore in Executing Cell Death (P2102)
Location
Petersplatz 1 Basel, Switzerland
Published
2021-10-07
Job type
PhD
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