Protein Structure and Function

Prokaryotic immune systems

Prokaryotes have evolved a diverse arsenal of immune systems that provide protection against the constant threat of invading nucleic acids such as viruses and plasmids. In the last decade, numerous different prokaryotic immune systems (e.g. CRISPR-Cas and prokaryotic Argonaute proteins) have been characterised. 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. Such 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 utilisation as programmable genome editing tools or nucleic acid detection tool has caused a revolution in basic biology research. Furthermore, these tools have a great potential for diagnostic purposes and 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.

Research questions

In the Swarts lab, we 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 recognise invaders?
• What catalytic mechanisms are employed to degrade invader DNA?
• What is the advantage of certain prokaryotic immune systems over other systems?
• Can certain immune systems be repurposed as molecular tools?

Techniques

To address our research questions, we 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 allows us to chart in detail the function and biochemical mechanisms of uncharacterized prokaryotic immune systems.