Institute of Physical Biology, Heinrich-Heine-University Duesseldorf
To understand life on a molecular level it is of fundamental importance to study structure and function of life's key players -proteins, nucleic acids and lipids - in their native environment.
Our main focus is to develop and apply tailored methods to overcome current limitations in structural biology and to obtain high-resolution insights into life's key players in an increasingly native setting.
Most biological processes are driven by (inter)actions of proteins. Protein function itself is diverse and in general associated with its three dimensional structure.
We are interested in the structural features of proteins that are embedded in the cell membrane as well as the molecular mechanism involved in protein folding and aggregation.
In particular we are investigating:
Structure and function of membrane systems:
Membrane proteins act as the central interface between environment and cellular response. Due to practical reasons high-resolution insights into membrane protein structure and function is often obtained by replacing the native lipid bilayer environment with detergent molecules.
We are using two approaches to circumvent intrinsic disadvantages of detergent systems:
- Solid-state NMR in a near native environment (i.e. proteoliposomes)
- Solution-state NMR in detergent free environments (e.g. lipid-bilayer nanodiscs)
Pathways of (membrane) protein folding:
- How does an unfolded, useless protein get into the (cell) membrane and does suddenly obtain its important function, such as regulation of blood pressure or appetite?
- And how does a harmless and useful protein end up in a state that causes severe damage to neuronal cells, which is linked to Alzheimer's or Parkinson's disease?
We are developing and applying new approaches to obtain high-resolution insights into structural and kinetic details which underlay and/or determine the pathways of membrane protein folding and amyloid fibril formation.
Methods to improve high-resolution insights into challenging biological systems:
In general NMR equipment is very expensive. Therefore it is important to optimize the use of available resources. We are developing experiments which enable nearly simultaneous detection of different NMR active nuclei, which can be used to significantly reduce expensive measurement time and additionally may offer unique insights into correlated biological processes.
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-
We aim to identify and apply the most suitable technique and (membrane) environment for a given system.
Therefore we are using on the one hand well-established test proteins such as bacteriorhodopsin to explore feasibilities and limitations of promising non-conventional tools such as nanodiscs and amphipathic polymers. On the other hand we make use of the obtained information to advance the characterization of more challenging and pharmacologically relevant membrane proteins. For the latter we are in particular interested in understanding the molecular mechanism involved in hormone-receptor interactions.