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University of Basel

PhD Position on Methods to understand the role of ordered waters and disordered residues in enzyme catalysis using macromolecular crystallography at physiological temperatures (P2104)

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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.
X-ray crystallography at cryogenic temperatures (100 K, Cryo-MX), has played an important role in the structural characterization of proteins, such as enzymes, channels and receptors. Roughly 90% of all crystal structures in the Protein Data Bank (PDB) have been recorded using deep-frozen protein crystals. Although highly successful with regard to solving structures free of radiation damage, it has gradually become clear that the protein conformations observed by Cryo- MX may not necessarily be physiologically relevant. Rapid cooling of the protein crystals can populate non-physiological conformations of proteins because enthalpically stabilized states dominate over high entropy states [1]. The rapid cooling process does not allow full equilibration, with the result that the observed structures may represent artificial conformations – neither biologically relevant nor thermodynamically favored [2]. Because polar interactions are temperature sensitive, the precise arrangements of protein residues, ligands and solvent molecules in the active sites of enzymes, channels and receptors are prone to significant change upon cryo-cooling. These changes can lead to false conclusions.
This project aims to implement room temperature (RT) crystallography methods to determine enzyme structures that are physiologically more relevant that those emerging from standard measurements at cryogenic temperatures.

[1] D. A. Keedy et al., "An expanded allosteric network in PTP1B by multitemperature
crystallography, fragment screening, and covalent tethering," Elife, vol. 7, 2018.
[2] M. Fischer, B. K. Shoichet, and J. S. Fraser, "One Crystal, Two Temperatures: Cryocooling Penalties Alter Ligand Binding to Transient Protein Sites," ChemBioChem, vol. 16, no. 11, pp. 1560–1564, Jul. 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 Methods to understand the role of ordered waters and disordered residues in enzyme catalysis using macromolecular crystallography at physiological temperatures (P2104)
Location
Petersplatz 1 Basel, Switzerland
Published
2021-10-07
Job type
PhD
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Our mission is to accomplish first-class research, teaching, and public service. We rank among the world’s one hundred best universities and boas...

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