Highly developed organisms rely on an intricate genetic program that allows them to differentiate from stem cells into genetically largely uniform but epigenetically highly diverse set of cell types. The latter establish the necessary structures and perform the different functions in the developing or adult organism. This fundamental biological problem is highly relevant to medicine. For example, erroneous changes related or mirrored in the gene program can alter the status of defined cell such that it adopts a pathological state. In the worst case such a change may be irreversible, leading for example to persistent inflammation or cellular transformation.
The department is interested in the fundamental principles of gene control in tumor and stem cells. A focus in the past has been on the mechanisms of gene transcription and the protein networks involved. We study model systems relevant to gene activation, cell differentiation and cell programming by oncogenes. Our goal is to understand the molecular programming of cells. Towards this goal we collaborate with the Max-Planck Institute for Molecular Biomedicine and groups in the Medical School. Together we share the vision that detailed insight into the mechanisms of gene programming as a consequence of signaling will be highly beneficial to designing strategies against diseases such as inflammation and cancer.
Historically, we have taken a biochemical approach to first isolate the protein involved in the control of gene transcription. We subsequently begun to study them on intact genes inside cells and ultimately in mouse models. One well studied result of this line of investigations is the transcription cofactor PC4, a small protein with unique structural and biological properties.
We continue to apply biochemical methods to study the molecular processes in transcription (Schlüsche et al., 2007). However, the applied method spectrum in the lab is broad ranging from standard molecular and cell biology techniques (Mortusewicz et al., 2008) to mouse genetics (Li, Roth et al., unpublished).
Furthermore, being interested in the global role of transcription factors and the general principles of epigenetic gene programming, we study defined processes inside cells using system biology technologies: examples are Chromatin IP of proteins bound to chromosomes (ChIP, Uhlmann et al., 2007), microarrays and genomewide binding of transcription factors (CHIPchip, Albert et al., 2007), ChiPseq (ongoing) as well as proteomics (Blazek et al., 2005).