Current Research Topics

DNA compaction and condensation

genome organizationThe meters of DNA in eukaryotic organisms are tightly packed into a higher-order structure called chromatin in order to fit in the tiny nucleus. The basic compaction unit of this condensed structure is a DNA-protein complex termed nucleosome which consists of a small piece of DNA wrapped around a core of so-called histone proteins. Besides packaging DNA, nucleosomes also play an essential role in the regulation of important nuclear processes such as transcription, replication and repair by controlling DNA accessibility. In this context nucleosomes are both highly ordered and dynamic as a result from the interplay between different processes such as DNA sequence-dependent positioning, thermal motion, remodeling and histone modifications in forms of different variants or posttranslational modifications. Using magnetic tweezers, we are investigating nucleosome structure and dynamics at single-molecule level.

DNA repair

chrom-hetero-DSB
DNA is constantly damaged in our own cells. Single-molecule techniques can help to examine the dynamics of the repair process.

DNA transcription and replication

Torque_dependence_section
DNA forms a double helix which is unwound during processes such as transcription and replication. Analogous to the unwinding of a twisted rope, this leads to the formation of large loops in the DNA, called supercoils. Molecular motors involved in transcription and replication thus help create these supercoils, but there are also enzymes called topoisomerases that remove them.

RNA transcription and replication

dsRNA
RNA is involved in many fundamental biological processes in addition to its well-known role as the messenger molecule between DNA and proteins. For example, RNA forms the genome of viruses and it underlies the process of RNA interference (the discovery of which was awarded the Nobel Prize in Medicine/Physiology in 2006). In both these cases the RNA acts in concert with many RNA processing enzymes, such as RNA-dependent RNA polymerases, ligases, and RNA nucleases.

Bacterial DNA replication

ecoli_replication2
In order for the bacterium Escherichia coli (E.coli) to proliferate it has to bi-directionally replicate its circular chromosome successfully. Multiple individual molecular machines known as replisomes are responsible for DNA synthesis. The exact dynamics of the replisome (and other enzymes) is not well understood. We use in vivo single-molecule fluorescence microscopy to study DNA replication in living E.coli cells.

Bacterial swimming

BFMBacteria are fascinating micro-organisms, capable of sensing their surroundings and propelling themselves towards favorable environmental conditions. In the case of Escherichia coli, this bacterium uses multiple flagellar filaments to propel itself. Each flagellar filament is rotated by a motor, one of the very few rotary motors found in nature. These bacterial flagellar motors (BFMs) are only 45 nm in diameter, yet can rotate at speeds of 100 Hz and generate torques over 1000 pN·nm. In our research, we aim to investigate the dynamics and mechanisms of this molecular motor using tweezers instrumentation.

Funding for this research is made available by:

  • European Research Council (ERC)
  • The Netherlands Organization for Scientific Research (NWO)
  • The Foundation for Fundamental Research on Matter (FOM)
  • European Union FP7
  • NanoNEXT NL

Past Research Topics

Single-molecule studies of topoisomerases