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The CIGR comprises research groups from the Institute of Biology Leiden (IBL), the Leiden Institute of Chemistry (LIC), the Leiden Academic Centre for Drug Research (LACDR) and the Leiden Institue of Physics (LION).

Dame Lab: Chromosome structure and function in bacteria and archaea

The Dame lab investigates the mechanisms by which the genomes of bacteria and archaea are structurally and functionally organized. The lab explores at the structural level how individual chromatin proteins act upon genomic DNA, how this translates into global organization of the genome inside life cells and how genome organization affects DNA transactions and vice versa. Of specific interest is how these processes are influenced by the cellular environment. The approach used combines molecular and cellular biochemistry with life cell imaging.

The Mashaghi Lab: Single molecule and circuit topology analysis of folded biomolecules

The Mashaghi Lab is interested in molecular folding processes at various scales ranging from single protein to the whole genome. We combine experimental and computational approaches to find folding mechanisms involved in neuromuscular diseases and cancer. The team uses optical tweezers to follow folding of single molecules in real time. The lab has also developed circuit topology, a technology that is uniquely suited for topological analysis of folded linear chains. Among others, the team is studying androgen receptor (AR) signaling in Spinal Bulbar Muscular Atrophy (SBMA) and prostate cancer. One important research question is how molecular chaperones mediates folding and assembly of proteins that regulate transcription (e.g., AR). The team collaborates with AstraZeneca for developing new therapeutic approaches using single molecule and topology methods.

The Schaaf Lab: The action of the Glucocorticoid Receptor

The Schaaf Lab studies the action of the Glucocorticoid Receptor (GR), which is an intracellular receptor, that can be activated by the stress hormone cortisol or by synthetic glucocorticoids such as dexamethasone and prednisolone that are clinically used as anti-inflammatory drugs. Upon activation by a ligand, this receptor acts as a transcription factor, binding to DNA, interacting with other proteins and modulating the transcription rate of target genes. The GR is studied in cultured cells and in living zebrafish. Using advanced fluorescence microscopy techniques, the mobility pattern of GRs inside the cell nucleus is analyzed, in order to reveal how GRs reach their DNA target sites and regulate transcription.

Van Noort Lab: Chromatin dynamics

In our lab we study the physics of chromatin organization. Chromatin plays an important role in maintaining our genome and in the regulation of activity of the genes that it contains. Its 3-dimensional organization of strings of nucleosomes into higher order structures is highly dynamic and has been challenging to grasp experimentally, obscuring a mechanistic picture of processes involving DNA. Using reconstituted chromatin fragments that are designed to include functionality such as specific sequencies, post-translational modifications, ligand binding sites and fluorescent probes, we aim to uncover the physics that directs chromatin folding. We also build custom microscopes tailored to resolve DNA-related processes at the single-molecule level with nanometer and milli-second accuracy. In addition, we use and develop statistical mechanics to advance the interpretation of the measured data, such as models that capture forced rupture of chromatin fibers, models that explain sequence preferences for nucleosome positioning and structural models using rigid base pair Monte Carlo simulations of chromatin.

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