Our research topics & methods

Virions are a fascinating class of pathogenic agents behind major infections afflicting humans. Some viruses encode for only a handful of proteins, which combine in multifunctional ways to sustain the life cycle of the virus. To this purpose, they assume polymorphic conformations and form transient interactions. This makes viral proteins challenging targets for investigations of molecular form and function.

We employ solid-state nuclear magnetic resonance (NMR) methods, complemented by solution-state NMR, electron microscopy, and related biophysical methods to investigate these intriguing biological assemblies.

Supramolecular organization of virions

Our goal is to understand the supramolecular organization of virions: the self-assembly of capsid proteins, their attachment to the lipid envelope, and the packaging of nucleic acids inside the capsid.

Schematic model of an enveloped virion. Not all building blocks are structurally well defined yet. Our mission is to fill in the gaps here.

 

A central line of our research is the accurate determination of biomolecular structure at atomic resolution. While many viral capsids are well characterized, structure elucidation of the heterogenous lipid membranes and embedded surface proteins of enveloped viruses is lacking behind. Combining spectroscopic and microscopic methods, we want to fill in these gaps.

The road from spectroscopy towards molecular structure, with illustrations taken from previous work (Chembiochem 11, 2010; Angew. Chem. 54, 2015).

 

Our research is not limited to static structural biology, though. Very little is known about elements of the virion that lack structure but do fulfill biological functions. This includes the motions of flexible protein segments and irregular capsid-envelope interactions. It extends to probing the chemical composition and physical properties of the lipid membrane in the virus envelope by spectroscopic techniques.

Targeting virion assembly with small molecules

A better structural definition of the virion can help identify starting points for the rational design of drug molecules that interfere with life cycle of the virus.

We investigate how small molecules can inhibit capsid assembly and interfere with capsid envelopment. The underlying goal behind this research is to identify new approaches to inhibiting the replication of the virus. To translate potential antiviral strategies into medical research, we maintain close collaborations with medical scientists and virologists, Prof. Ulrike Protzer at Klinikum Rechts der Isar in Munich and Prof. Volker Bruss at Helmholtz Center Munich.

 

Structure-guided drug design (Angew. Chem. 50, 2011; Sci. Transl. Med. 7, 2015; ACS Chem Neurosci., 2017).