1. Developing methods to study dynamics of chromatin regulation
The structure of chromatin is organized over many length scales and highly dynamical. Its function is modulated by the combinatorial effect of histone post-translational modifications (PTMs). Specialized reader proteins interpret combinations of PTMs and result in structural transition in chromatin, recruitment of cellular machinery and gene regulation.
We develop chemical methods to site specifically introduce PTMs and fluorescent labels into reconstituted synthetic chromatin fibers to study conformational dynamics in chromatin as a function of histone marks (e.g. ubiquitylation) and structural reader proteins on the single molecule scale.
We are interested in how proteins readers find their site of action in the highly complex environment of the cell. Thus, we characterize the binding thermodynamics and binding kinetics of protein readers with modified chromatin in vitro and study their diffusional properties and localization in cells.
Multivalency governs HP1α association dynamics with the silent chromatin state, 18 Jun 2015 | doi:10.1038/ncomms8313
2. Deciphering the molecular basis of gene activation
How doe transcription factors, chromatin remodelers and the RNA polymerase collaborate to activate genes? Here, we use a combination between chemical biology, single-molecule biophysics and cell imaging to unravel dynamic processes in gene control with molecular details.
3. Chemical biology of chromatin and the cytoskeleton
The study of the function of post-translational modifications requires access to chemically defined samples. Thus, we develop and apply novel chemical methods to site-specifically modify chromatin proteins, e.g. controlling the ubiquitylation state, and cytoskeletal proteins such as tubulin.