Current Job Openings
We have currently two openings for a PhD student or Master thesis project:
AA amyloidosis and serum amyloid A (SAA)
In collaboration with the group of Prof. Marcus Fändrich, Universität Ulm, we investigate aggregates formed by the protein SAA. AA amyloidosis is a protein misfolding disease that affects humans and animals (Westermark et al., 2015, Obici & Merlini, 2012). The disease accompanies chronic inflammatory conditions, such as rheumatoid arthritis, leprosy or tuberculosis. Its amyloid fibrils consist of AA protein, which represents mostly a 76 amino acid fragment from the N-terminus of SAA1 protein. SAA1 is an extracellular blood apolipoprotein that becomes strongly upregulated during inflammation.
It will be the goal of the study to obtain a structural model of a monomer in the SAA1 fibril based on solid-state NMR and to perform an integrated structural analysis using solid-state and cryo-EM data.
image: Lu et al. (2014) Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis. Proc. Natl Acad. Sci. U.S.A. 111: 5189-5194.
Binding of PET tracer molecules in neurodegenerative diseases
In collaboration with the groups of Prof. Hans-Jürgen Wester and Dr. Behrooz Yousefi at the TUM, we investigate how PET tracer molecules interact with Alzheimer's disease Aβ and Parkinsons's disease α-synuclein aggregates. PET tracer molecules are diagnostic markers that allow to recognize early-on a particular neurodegenerative disease. So far it is not easily possible to differentiate between different neurodegenerative diseases. Wester and Yousefi have now designed bithiazole derived small molecules that have strongly different binding properties to Aβ and α-synuclein, respectively (Yousefi et al., ACS Med. Chem. Lett. 2011; Yousefi et al., ACS Chem. Neuroscience 2015), that are employed for detection of amyloid deposits in vivo.
It will be the aim of the project to determine the atomic level structure of the small molecule - aggregate complex using MAS solid-state NMR, and to suggest small molecule derivatives with improved binding properties.
image: Dr. Behrooz Yousefi, Prof. Hans-Jürgen Wester, TUM
Development of MAS solid-state NMR methods
We aim to characterize dynamic processes in immobilized proteins. In particular, we want to quantify order parameters and relaxation rates, as well as interpret these observables in a model-dependent framework. see e.g.
Asami, S. & Reif, B. (2013). Proton-detected solid-state NMR at aliphatic sites: Applications to Crystalline Systems. Acc. Chem. Res. 46, 2089-2097.
Chevelkov et al. (2009) Analysis of the Dynamics of Backbone Motion in the Solid-State. J. Biomol. NMR 45, 197–206.
image: 800 MHz solid-state NMR spectrometer with DNP unit at the Bayerisches NMR-Zentrum, Helmholtz-Zentrum in Neuherberg.