PhD position in Electron Microscopy/Membrane Enzymology

Updated: about 2 months ago
Deadline: 03 Jul 2019

We are looking for a talented and enthusiastic biologist, chemist, biochemist or physicist who is interested in studying the structure-function relationship of membrane transporters. Membrane proteins compromise more than 60% of today’s pharmaceutical drug targets. In our group, we employ mostly single-particle cryo-EM, which we complement with the biochemical characterization of the target protein to unravel its mechanism of action. Many of our targets have a direct pharmacological relevance and our results might guide structure-based drug design.

You will be working at the Electron Microscopy group led by Dr Cristina Paulino, which is part the GBB Departments of Structural Biology and Biochemistry. We are equipped with an in-house Talos Arctica (auto-loader, K2, energy filter and phase plate), which allows us to obtain high-resolution data of small membrane proteins (115-250 kDa, low or none symmetry). You will have an exceptionally high access to the microscope and will be thoroughly trained. If required there is also access to two Titan Krios microscopes at NeCEN (the Dutch EM facility in Leiden).

Recent papers include:
1. Alvadia, C. et al. Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F. Elife 8, 213 (2019).
2. Kalienkova, V. et al. Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM. Elife 8, 213 (2019).
3. Stock, C. et al. Cryo-EM structures of KdpFABC suggest a K+ transport mechanism via two inter-subunit half-channels. Nat Comms 9, 4971 (2018).
4. Garaeva, A. A. et al. Cryo-EM structure of the human neutral amino acid transporter ASCT2. Nat Struct Mol Biol 25, 515–521 (2018).
5. Paulino, C., Kalienkova, V., Lam, A. K. M., Neldner, Y. & Dutzler, R. Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM. Nature 552, 421–425 (2017).

You will receive excellent training through cutting-edge research projects, advanced courses and training opportunities, complemented by workshops on generic research, transferable skills and teaching. As a PhD candidate, you are committed to conduct independent and original scientific research, to report on this research in international publications and presentations, and to present the results of the research in a PhD dissertation, to be completed within 4 years. You are expected to contribute 10% of their overall workload to teaching.


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