Dynamic Nuclear Polarization for Biology and Chemistry
We develop Dissolution Dynamic Nuclear Polarization (D-DNP) solutions for applications to biological and chemical problems.
Dissolution Dynamic Nuclear Polarization (D-DNP) is a method to dramatically amplify Nuclear Magnetic Resonance (NMR) signals by over 4 orders of magnitude.
Employing D-DNP, we develop solutions for physiological real-time NMR by exploiting the enhanced signals to reduce detection times and required substrate quantities.
We aim at including D-DNP into an integrative framework comprising Nuclear Magnetic Resonance and Electron Paramagnetic Resonance to characterize biochemical systems from various viewpoints on a wide range of length and time scales. We investigate several systems ranging from Transcriptions Factors over biominerals to small molecules.
Nuclear magnetic resonance (NMR) spectroscopy is currently the only high-resolution method for the elucidation of structural dynamic of proteins and nucleic acids in solution. We apply dissolution dynamic nuclear polarization (D-DNP) to improve NMR of proteins — a method coined HYPEX (hyperpolarization exchange spectroscopy) where hyperpolarized aqueous buffer boosts NMR signals by several orders of magnitude. HYPEX NMR enables time-resolved studies of macromolecules under physiologically relevant conditions and allows the determination of interaction kinetics.
Because it follows non-classical crystallization mechanisms, biomineral nucleation –where soluble prenucleation inorganic species evolve into mineral phases under strict protein control– remains intensely debated. This project will
mechanistically determine how mineralizing proteins regulate the structure and dynamics of prenucleation inorganic species throughout early apatite formation, from the solution to the nucleation of the solid phase.
Unveiling these mechanisms will shed light onto the critical early stages of apatite formation with unprecedented spatio-temporal resolution, and may also increase the comprehension of bone pathologies triggered by anomalous mineral nucleation events.
Whilst NMR detects nuclei in biomolecules, electron paramagnetic resonance (EPR) is sensitive to special paramagnetic protein tags. EPR and NMR are complementary magnetic resonance techniques with respect to time and length scales resolving together a wide range of distances from 0.1 Å to 10 nm and motions on picoseconds to seconds scales. We develop applications for integrative EPR and NMR for protein structural biology, which grants deep insights into the structural dynamics of folded as well as intrinsically disordered proteins (IDPs).