PhD positions in the field of NMR supported structural biology

22.01.2024, Wissenschaftliches Personal

The Reif group at the Bavarian NMR Center (BNMRZ) has 2 PhD student positions available to start immediately: 1) Characterization of the protein aggregation using a combination of solution- and MAS solid-state NMR 2) Development of MAS solid-state NMR methods

1) Characterization of the 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) involved 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
For further information, please see our web page: https://www.bio.nat.tum.de/ocb/home/.
Our group is integrated into the Bavarian NMR Center (www.bnmrz.org) at the Technical University Munich, and is associated with the Institute of Structural Biology (www.helmholtz-munich.de/en/stb) at the Helmholtz-Zentrum München (HMGU). Labs are located in the Bavarian NMR Center at Campus Garching, together with the Groups of Prof. Sattler, Prof. Hagn and Prof. Glaser. In addition to a high-end NMR facility, our group has direct access on campus to a X-ray crystallography facility, 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.

The position is suitable for disabled persons. Disabled applicants will be given preference in case of generally equivalent suitability, aptitude and professional performance.

Data Protection Information:
When you apply for a position with the Technical University of Munich (TUM), you are submitting personal information. With regard to personal information, please take note of the Datenschutzhinweise gemäß Art. 13 Datenschutz-Grundverordnung (DSGVO) zur Erhebung und Verarbeitung von personenbezogenen Daten im Rahmen Ihrer Bewerbung. (data protection information on collecting and processing personal data contained in your application in accordance with Art. 13 of the General Data Protection Regulation (GDPR)). By submitting your application, you confirm that you have acknowledged the above data protection information of TUM.

Kontakt: If you are interested, please send an email with a copy of your CV and certificates to Prof. Dr. Bernd Reif, email: [email protected]