Nordenskiöld, Lars


Nordenskiold, Lars

Nordenskiöld, Lars

Office: 01n-17 / 04s-31
Telephone: 6592 7506 / 6316 2856



  • B.Sc. - Stockholm University (1976)
  • Ph.D. - Stockholm University (1981)

Professional Experience

  • Post doctoral stay at University of Wisconsin-Madison, USA, 1982-1983.
  • Faculty appointment at Stockholm University, Division of physical chemistry, 1983-2002.
  • Full professor in physical chemistry at Stockholm University, from 2000.
  • Professor at School of Biological sciences, NTU, Singapore from 2002.

Research Interest

Chromatin Biochemistry and Biophysics: Mechanisms and Regulation of Chromatin Compaction

Eukaryotic genomic DNA is condensed into chromatin: 146bp DNA wraps around the histone octamer (HO) comprising two copies each of the core histones H2A, H2B, H3 and H4 forming the nucleosome core particle (NCP). A string of nucleosomes folds into the so-called called “30nm” chromatin fibre, which compacts into metaphase chromosomes (Fig. 1).
Human telomeres constitute the protective structure at the end of the chromosomes with repetitive TTAGGG sequences that are about 10kbp. Little is known about the consequences of this unique sequence for chromatin structural and dynamic properties. Although it is established that telomeric DNA is packaged in chromatin with an unusually short (157 bp) nucleosome repeat length (NRL) and can form nucleosomes and chromatin, almost nothing is known about the telomeric nucleosome core and telomeric chromatin structure at the detailed molecular level.
A general aim of our research is the unravelling of the principles and control of the packaging of DNA in the cell nucleus within the context of chromatin with emphasis to the unique telomeric chromatin. We are interested in understanding the molecular interactions and the (electrostatic) mechanisms that induce, stabilize and regulate chromatin folding and what are the implications of this for gene regulation.
Some specific aims are:
  • To experimentally and theoretically investigate the folding of recombinant in vitro prepared nucleosome core particles (NCP) and well-defined chromatin in the form of nucleosome arrays and how this is affected by changes of the histone tail modifications and transcription factor binding with applications to telomeric chromatin.
  • To identify the difference in structure and dynamics between telomeric and “normal” canonical nucleosomes and chromatin, using biophysical and structural methods like X-ray crystallography, EM and solid-state NMR (Fig. 2).
  • To characterise the binding and structural and dynamic properties of HP1 interaaction with telomeric chromatin and compare it with canonical chromatin
  • To establish the physical basis in terms of electrostatic/molecular interactions for DNA interactions, structure and dynamics within the context of chromatin using modelling tools.
These aims are realized by using a combination of molecular biology, biochemical and chemical synthesis techniques in combination with biophysical approaches such as single molecule measurements (magnetic tweezers), solid-state NMR, synchrotron x-ray diffraction (SAXS), analytical ultracentrifugation, as well as well as Electron (EM) methods. Experimental work is often performed in combination with our computer modelling studies.
  1. Telomeric chromatin: Unravelling the structural properties of the telomeric nucleosome and chromatin and how it differs from non-telomeric chromatin. We are part of the interdisciplinary international Telomere Dynamics Group (TDG) research programme (here).
  2. Understanding the structural and dynamic properties of condensed heterochromatin within the context of telomeres. Specifically, the role of heterochromatin protein 1 (HP1) by solid-state NMR study of heterochromatin maintenance by HP1 protein at telomeres
  3. Multi-scale computer modeling of electrostatic interactions in DNA, the nucleosome core particle (NCP), chromatin up to mesoscale megabase size chromosomal chromatin for an understanding of nuclear 3D architecture.

Figure 1. (A). The structure of the nucleosome core particle (NCP). (B) NCPs connected by linker DNA forming a “bead-on-a-string”, 10-nm chromatin fibre. (C) Schematic illustration of chromatin folding into the 30-nm fibre. (D). Chromatin folding to higher-order structures.

Figure 2. Crystal packing in the 2.1 Å 145 bp human telomeric NCP crystal in comparison with 2CV5 structure (human histone octamer and 146 bp palindromic α-Sattelite DNA). Telo-NCP is shown in blue and 2CV5 is shown in red.