Research in my lab is focussed on structural and/or biological questions that can be solved by Nuclear Magnetic Resonance.  In parallel, we additionally employ a diverse range of biochemical, biomolecular and bioinformatics techniques to develop a comprehensive understanding of the studied systems.

Structural Biology

To understand cellular processes on a molecular level the 3D structures of the respective proteins have to be known. NMR spectroscopy is a versatile technique both for elaborate structure determination and for fast interaction studies e.g. for ligand screening. It is also possible to determine dynamical aspects of the studied systems at atomic resolution. We have studied a diverse range of proteins with the aim to understand how protein function is related to structure and dynamics. Current main activities of my lab center on the interplay between structure and dynamics of γ-secretase substrates, topic of the DFG funded research group FOR2290 “Understanding intramembrane proteolysis”. The intramembrane protease γ-secretase is a key player in Aβ plaque generation that occurs during Alzheimer’s disease. Studies of my lab suggest that substrate recognition is linked to the pliability of the transmembrane helices (Silber et al. 2020).

Fig 1: Docking of the structural bundle of APP-TM into a model of presenilin, the catalytic unit of γ-secretase.  

Metabolomics

Metabolites are products of cellular processes that are found in organisms and body fluids. The composition of the metabolome, the sum of all metabolites, varies with many factors like the developmental state of the organism, malnutrition or disease.

We employ NMR spectroscopy paired with statistical analyses to investigate body fluids like urine or blood or extracts of cells or whole organs. In this way, we determine the chemical fingerprint of the studied systems. Our aim is to develop diagnostic tools for disease recognition or for studying the effect of chemicals or drugs on the organism. As a non-targeted approach, all sufficiently concentrated metabolites with hydrogen atoms contribute to the data.

In this way, we explored markers for acute kidney disease in children (Muhle-Goll et al. 2020) or how well blood metabolites are removed by hemodialysis (Kromke et al. 2016).

We collaborate with biologists and clinicians at KIT and the university of Heidelberg (https://www.3dmattermadetoorder.kit.edu/), who  provide us with the biological and medical samples . E.g. we currently work on the identification of specific metabolites that may govern derivation of retinal organoids (https://www.3dmattermadetoorder.kit.edu/phds_771.php)