DNA contained in the cell is wrapped around histones to form nucleosomes, which are compacted into higher order chromatin structures. The DNA within chromatin must be made accessible for many DNA-based transactions to occur including transcription, replication and DNA repair. An important property of DNA, which is often overlooked, is that it is not static. Rather, it moves within the cell. The origin and function of this movement remain mysterious and cannot be explained solely by Brownian motion. The problem is further complicated by forces that act on the nucleus, generated by microtubules and actin fibers. However, we do know that molecular machines called chromatin remodelers can change the shape and organization of DNA and influence its dynamics
The Seeber laboratory focuses on understanding how changes in chromatin structure modulate its dynamics and impact its function. We develop new microscopy techniques and analysis methods to study chromatin in living human cells and apply these techniques to biological questions. In particular, we study how chromatin dynamics affect DNA repair. This ultimately allows us to better understand the processes that lead to DNA mis-repair, mutations and translocations.
Figure 1 - A) DNA contained in the cell is wrapped around histones to form nucleosomes, which are compacted into higher order chromatin structures – image courtesy of Mol. Bio. of the Cell, 2002. B) A yeast nucleus where the nuclear pores have been labeled with Ruby2 and a chromatin locus has been visualized with GFP-LacI. C) The Seeber laboratory collaborates with polymer physicists to model chromatin based on biological experiments. Displayed is the β-polymer model which predicted chromatin expansion at the site of a DNA double-strand break (see Amitai, Seeber et al, 2017). D) Day to day analysis of microscopy data is done using Fiji (ImageJ), MATLAB, R and KNIME. E) We study how chromatin can be modulated to either facilitate or inhibit DNA double-strand break repair (reviewed in Seeber et al, 2018 Annual Review in Genetics).