Jetzt als 2 PhD student positions open bei Technische Universität München starten

We are looking for 2 PhD students:

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 affect 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 microsocopy and dynamic light scattering (DLS).

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.

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 Multidimensional Solid-State NMR Spectroscopy by Optimal-Control-Based Transverse Mixing Sequences. J. Am. Chem. Soc. 144: 17336-17340; doi: 10.1021/jacs.2c06568.

Our group is integrated into the Bavarian NMR Center (www.bnmrz.org) and is associated with the Institute of Structural Biology (www.helmholtz-munich.de/en/stb) at the Helmholtz-Zentrum München. We offer flexible working hours and friendly atmosphere. Labs are located in the Bavarian NMR Center at Campus Garching (behind the chemistry building) together with the Groups of Prof. Sattler, Prof. Hagn and Prof. Glaser. While working at BNMRZ, you participate in the scientific seminars organized by the BNMRZ, STB and SFB and become a part of the Structural biology and NMR world.

Kontakt: reif@tum.de

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