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Technical University of Munich

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PhD position (TVöD E13, 66 %)

18.06.2019, Wissenschaftliches Personal

Within the DFG Research Unit 2969 "Mechanisms of antibody light chain misfolding in systemic AL amyloidosis", we are looking for a motivated biochemist/biophysicist interested in NMR

Light chain or AL amyloidosis is one of the most abundant types of systemic amyloidosis. Advanced kidney or heart involvement can lead to rapid dialysis or death. The disease is caused by the misfolding and aggregation of antibody light chains, which are produced in the course of a monoclonal B-cell disorder. A particular remarkable feature of AL amyloidosis is the variability of its clinical manifestations. This heterogeneity is probably caused by the natural diversity of light chains and of the polymorphic aggregate structure. However, the exact relationships are so far not understood.

The PhD project involves solution-state and MAS solid-state NMR to characterize (i) the structure and misfolding of full-length light chains, (ii) the misfolding kinetics of the AL proteins and (iii) the structure of AL protein aggregate fibrils. Furthermore, the structural properties of proteins derived from AL patients with proteins derived from multiple myeloma without AL amyloidosis shall be compared. Analysis of the interactions between the variable light and the constant light domain will give insights whether or not these interactions interfere with the further processing of the light chains. Comparison of structures obtained from differing sequences shall enable the derivation of more general principles for AL amyloid fibril formation.

The Bayerische NMR-Zentrum is a joint infrastructure of the TU München and the Helmholtz-Zentrum München. The center is well equipped with state-of-the-art solution-state and MAS solid-state NMR spectrometers at magnetic field strengths ranging from 250 MHz to 950 MHz. A biochemical laboratory is available for molecular biology, biochemistry and biophysical work. New office and lab space provides excellent working conditions (move into a new building in 2017).

To apply, you should hold a Master degree in chemistry, biochemistry or physics. Experience in Nuclear Magnetic Resonance is beneficial. Interest in NMR supported biomolecular structural biology is essential. The PhD position is guaranteed for two years, and can be extended up to 4 years upon mutual agreement.

In order to apply, please send your documents (CV, copy of certificates) via email to
Prof. Dr. Bernd Reif
Technische Universität München (TUM)
Department Chemie, Festkörper-NMR Spektroskopie
Lichtenbergstr. 4, 85747 Garching, Germany
Tel.: +49 89 289 52615
Email: reif@tum.de
web: http://www.ocb.ch.tum.de
http://www.bnmrz.org

Literature
1) Hora M, Sarkar R, Morris V, Xue K, Prade E, Harding E, Buchner J, Reif B (2017) Antibody light chain fibrils are similar to oligomeric precursors. PloS one 12: e0181799.
2) Hora M, Carballo-Pacheco M, Weber B, Morris VK, Wittkopf A, Buchner J, Strodel B, Reif B (2017) Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains. Sci. Rep. 7: e41515
3) Close W, Neumann M, Schmidt A, Hora M, Annamalai K, Schmidt M, Reif B, Schmidt V, Grigorieff N, Fändrich M (2018) Physical basis of amyloid fibril polymorphism. Nature Commun. 9: 699.
4) Weber B, Hora M, Kazman P, Göbl C, Camilloni C, Reif B, Buchner J (2018) The antibody light chain linker is an important regulator for the orientation and stability of the two constituent domains. J. Mol. Biol. 430: 4925–4940.

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: Prof. Dr. Bernd Reif, email: reif@tum.de

More Information

http://www.ocb.ch.tum.de