2 openings for PhD positions

The Reif group at the Technical University Munich (TUM) in Garching, Germany, has 2 openings for PhD positions that are available immediately

1) Characterization of protein aggregation using a combination of solution- and MAS solid-state NMR

We aim to better understand the structural mechanism that underlies protein aggregation and amyloid formation. In particular, we investigate small molecules, chaperones, and cellular components such as glycosaminoglycans that influence the aggregation behaviour and effect amyloid fibril structure and cellular toxicity. Protein systems under investigation involve the Alzheimer’s disease Aβ peptide, the diabetes type II related human islet amyloid polypeptide (hIAPP), light chain antibody domains involved in AL-amyloidosis and serum amyloid A (SAA) in AA-amyloidosis. We employ solution- and MAS solid-state NMR to characterize these systems. In addition, we use low resolution biophysical methods such as fluorescence microscopy, ThT aggregation assays, CD spectroscopy, negative-stain electron microscopy and dynamic light scattering (DLS). Interested candidates should have a strong background in biochemistry and biophysical methods to characterize protein misfolding.

References

Sundaria A, Liberta F, Savran D, Sarkar R, Rodina N, Peters C, Schwierz N, Haupt C, Schmidt M, Reif B (2022) SAA fibrils involved in AA amyloidosis are similar in bulk and by single particle reconstitution: A MAS solid-state NMR study. J. Struct. Biol. X 6: e100069; doi: 10.1016/j.yjsbx.2022.100069.

Pradhan T, Sarkar R, Meighen-Berger KM, Feige MJ, Zacharias M, Reif B (2023) Mechanistic insights into the aggregation pathway of the patient-derived immunoglobulin light chain protein FOR005. Nat. Commun. 14: e3755; doi: 10.1038/s41467-023-39280-0.

2) MAS solid-state NMR methods

Solid-state NMR experiments are intrinsically insensitive, since magnetization is transferred via orientation dependent anisotropic interactions. In addition, the applied rf fields are time dependent due to sample rotation. It is thus impossible to find analytical solutions. In particular, high dimensional experiments involving many magnetization transfer steps suffer from low sensitivity. Optimum control derived strategies allow to overcome this problem and increase the sensitivity of each magnetization transfer step significantly, with gains on the order of x2-3 per transfer. It will be aim of the PhD project to experimentally measure the rf field distribution in fast-spinning MAS probes using pulsed field gradients. In addition, the concept of sensitivity improvement by exploiting coherence order selection shall be implemented in homo- and heteronuclear triple resonance rf pulse schemes to yield a suite of high-sensitivity sequential backbone assignment experiments. The PhD thesis project will be carried out in collaboration with the group of Zdenek Tošner, Charles University, Prague. Interested candidates should have a strong background in physical chemistry, including quantum mechanics. Theoretical and practical experience with NMR will be an advantage.

References

Tošner Z, Brandl MJ, Blahut J, Glaser SJ, Reif B (2021) Maximizing efficiency of dipolar recoupling in solid-state NMR using optimal control sequences. Sci. Adv. 7: eabj5913; doi: 10.1126/sciadv.abj5913.

Blahut J, Brandl MJ, Pradhan T, Reif B, Tosner Z (2022) Sensitivity-Enhanced Multi-dimensional Solid-State NMR Spectroscopy by Optimal-Control-Based Transverse Mixing Sequences. J. Am. Chem. Soc. 144: 17336-17340; doi: 10.1021/jacs.2c06568.

General Information 

Our group is integrated into the Bavarian NMR Center (www.bnmrz.org) of the Technical University Munich (TUM), and is associated with the Helmholtz-Zentrum München (HMGU), Institute of Structural Biology (www.helmholtz-munich.de/en/stb). Labs are located in the Bavarian NMR Center at the TUM campus in Garching, and shared with the groups of Michael Sattler, Franz Hagn and Steffen Glaser. In addition to a high-end NMR facility, our group has direct access on campus to X-ray crystallography, as well as to a cryo-EM platform equipped with a Selectrix X imaging filter and a modern Falcon 4i direct electron detector enabling cutting-edge single-particle analysis and in situ cryo-electron tomography. While working at BNMRZ, you participate in the scientific seminars organized by the BNMRZ, the STB and the cooperate research center SFB1035.

If you are interested, please send an email with a copy of your CV and certificates to reif@tum.de.