PhD in the field of NMR supported amyloid and bio-condensate structural biology

08.04.2024, Wissenschaftliches Personal

The Reif group at the Bavarian NMR Center (BNMRZ) at the TU Munich is looking for a PhD student to work on the characterization of amyloid fibrils, protein condensates and liquid liquid phase separation (LLPS) using a combination of solution- and MAS solid-state NMR spectroscopy. The position is available immediately.

General description
Membraneless organelles (such as nucleoli, nuclear speckles, stress granules etc.) are vital for living organisms. These biomolecular condensates are formed by multi-domain proteins that are involved in multi-valent interactions. Condensate formation implies both protein-protein and protein-RNA interactions, involving prion-like low complexity regions and RNA binding domains. The delicate balance between liquid-liquid phase separation (LLPS) and amyloid fibril formation requires tight regulation. This can be achieved by chaperones, posttranslational modifications, small molecules and/or metals that affect this balance and either yield disintegration or rigidification of protein liquid droplets into β-strand rich protein fibrils. It is the aim of the PhD project to better understand the mechanisms that modulate the equilibrium between amyloid fibril and granule formation in the cell on a structural basis. Protein systems under investigation involve stress granule (SG) associated factors, the Alzheimer’s disease Aβ peptide, the diabetes type II related human islet amyloid polypeptide (hIAPP/amylin), 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, 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. Nature Comm. 14: e3755; doi: 10.1038/s41467-023-39280-0.

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, and are used together with the groups of Profs. Michael Sattler, Franz Hagn and Steffen 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 (https://www.sfb.tum.de/en/1035/aktuelles/).

Start: 04/08/2024
End: 05/30/2024

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:
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Kontakt: Interested candidates send an email with a copy of your CV and certificates to Prof. Dr. Bernd Reif, email: [email protected]

https://www.bio.nat.tum.de/ocb/home/