Membrane systems in neuronal signalling:
Membranes act as the central interface between environment and cellular response. As such membrane proteins are the most frequent targets of modern drugs. In addition, also the lipids themselves can directly modulate biological processes.
We investigate the molecular mechanisms underlaying central neuronal communication pathways. The key players in this interaction network are (i) membrane protein receptors (GPCRs), (ii) neuropeptides, and (iii) lipid-membranes. We are in particular interested in deciphering:
- - How do neuropeptides and hormones talk to their receptors?
- - How are these signaling events modulated by the lipid membrane?
- - What role does the membrane play in neurodegenerative diseases?
For high-resolution insights we predominantly make use of the power of NMR spectroscopy including its wide range of useful sub techniques. However, to reliably answer the above questions, integrative approaches that combine most suitable biophysical and biochemical techniques are required.
Using a combination of solution- and solid-state NMR, fluorescence- and surface-based techniques, as well as molecular dynamic simulations, we recently could e.g. connect membrane binding modes with aggregation of the protein alpha synuclein, a process linked to Parkinson's disease. - see e.g. Viennet et al. Commun Biol. 2018, and Falke et al. Chem Phys Lip 2019, for more details.
NMR method development:
While NMR has the potential to obtain atomic-resolution insights into native biological systems, most NMR methods face increasing limitations when sample complexity is approaching native conditions. Our NMR method development therefore aims to provide improvements that are in particular useful for challenging biological systems.
Our recently developed UTOPIA NMR setup allows e.g. the acquisition of relaxation favorable 13
C and 15
N spectra during the acquisition of the conventional 1
H detected spectra. The additional spectra can be obtained for free and contain otherwise not accessible information.
- see e.g. Viegas et al. JbNMR 2016, for more details.
UTOPIA NMR support:
The current UTOPIA version is v0.9. Please contact us via email to receive current beta-versions of sequences and support. -Send Mail-
In general, NMR is also applicable directly in cellular environments. However, cellular NMR's limitations comprise mainly signal sensitivity as well as selectively of the protein of interest. Combining the sensitivity boost of dynamic nuclear polarization (DNP) with the selectivity of protein interactions, both limitations can be reduced enabling the investigation of a target protein in a cellular context.
- see e.g. Viennet et al. Angew Chem 2016, for more details.