Andrzej Stasiak
DNA and Chromosome Modelling Group
University of Lausanne
Group Webpage

What do we do?

At the DNA and Chromosome Modelling Group we apply Metropolis Monte-Carlo and Brownian dynamics simulations to elucidate how DNA molecules and chromatin fibres behave in living cells. Our group is especially interested in understanding chromosome structure and organization during interphase. We investigate effects of high crowding such as those known to occur in cell nuclei. We study consequences of transcription-induced supercoiling and topological consequences of DNA replication. We build relatively simple models of interphase chromosomes that recapitulate the results of Chromosome Conformation Capture (3C) experiments.

Highlights 2016

  1. Using the Metropolis Monte-Carlo approach, we simulated supercoiled DNA molecules that were also knotted or catenated. The analysis of the obtained configurations suggested a geometric selection mechanism permitting bacterial DNA topoisomerases to efficiently decatenate freshly replicated DNA. Our study may help in the design of antibiotics which target bacterial topoisomerases.
  2. In a collaboration with researchers in Poland, we used bioinformatics tools to analyze proteins that form deep, tight knots. We observed that knotted cores in these proteins have somewhat unusual properties. These regions show an increased number of inter-residue contacts, have high thermal stability and low solvent accessibility.
  3. Due to our numerous publications in which we simulated DNA molecules, chromatin fibers and topoisomerases, we were invited by Methods in Molecular Biology to formally present various simulation methods used by our group in the form of protocols.

Main publications 2016

  • Rawdon E J, Dorier J, Racko D, Millett K C, Stasiak A. How topoisomerase IV can efficiently unknot and decatenate negatively supercoiled DNA molecules without causing their torsional relaxation. Nucleic Acids Res 2016; 44(10): 4528-38.
  • Dabrowski-Tumanski P, Stasiak A, Sulkowska J I. In search of functional advantages of knots in proteins. PLoS ONE 2016; 11, e0165986.
  • Racko D, Benedetti F, Dorier J, Burnier Y, Stasiak A. Molecular dynamics simulations of supercoiled, knotted and catenated DNA molecules including modeling of action of DNA gyrase. Methods in Molecular Biology (volume on Bacterial Nucleoid) Springer Science + Business Media, New York, in press, 2016.

Our research topics: