Our Group Is Looking for 2 Phd Students in The
vor 3 Wochen
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
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
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.
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