Laboratory of Biochemistry - Protein structure and function

From January 2019, a new research group will start at the Laboratory of Biochemistry. The research focus of this group will be the functional, structural, and mechanistic characterization of protein complexes that control prokaryotic immunity.

Prokaryotes have evolved a diverse arsenal of immune systems that provide protection against the constant threat of viruses and plasmids. In the last decade, various prokaryotic immune systems (e.g. CRISPR-Cas and prokaryotic Argonaute proteins) have been characterized. An important aspect of the functionality of both CRISPR-Cas and Argonaute systems is that the effector proteins of these systems can be (re)programmed with small nucleic-acid guides. These guides allow for sequence-specific recognition of invading DNA. These prokaryotic immune systems are not only interesting from fundamental biology and evolutionary biology perspectives, but their utilization as programmable genome editing tools has additionally caused a revolution in basic biology research and holds great potential to treat genetic diseases in the future.

Although certain prokaryotic immune systems are well studied, there is tremendous diversity, and most systems remain poorly characterized. We are interested in the diversity of these systems from a fundamental perspective.

The group will focus on research questions such as:

  • How do prokaryotic immune systems protect their host?
  • How are the macromolecular architecture and functionality of these systems connected?
  • How do proteins specifically recognize nucleic acids?
  • What catalytic mechanisms are employed to degrade invader DNA?
  • What is the advantage of certain prokaryotic immune systems over other systems?

    To address these questions, we will employ research techniques from various fields including bacterial genetics and biochemistry. In addition, X-ray crystallography is used to determine the macromolecular structures of proteins in complex with the nucleic acids that they interact with. Combined, this will allow us to chart in detail the function and biochemical mechanisms of uncharacterized prokaryotic immune systems.

    Cytosine recognition by Thermus thermophilus Argonaute   (Swarts, Szczepaniak, Sheng et al. (2017) Molecular Cell; PDB: 5GQ6)
    Cytosine recognition by Thermus thermophilus Argonaute (Swarts, Szczepaniak, Sheng et al. (2017) Molecular Cell; PDB: 5GQ6)
    Francisella novicida CRISPR-Cas12a in complex with crRNA and double stranded DNA target (Swarts et al. (2017) Molecular Cell; PDB: 5NFV)
    Francisella novicida CRISPR-Cas12a in complex with crRNA and double stranded DNA target (Swarts et al. (2017) Molecular Cell; PDB: 5NFV)