The area of protein-nucleic acid interactions is wide and it thus appears wise to concentrate the limited resources to support research lines that are grounded on established areas of excellence in Munich, but develop into the most challenging areas of general interest. We see two areas where these conditions would be met: (a) the regulatory potential of protein-RNA interactions; and (b) the regulation of genome function (transcription, replication, repair in collaboration with the groups working in the research areas C and E, particularly Cramer and Carell) during cell differentiation and organismic development through epigenetic principles. Since regulatory RNA emerges as an important determinant of gene regulation in chromatin both research avenues can be profitably combined by developing the area of epigenetic regulation of cell identity. This requires the analysis of cell-type specific variation of epigenome organization at the levels of chromatin structure and nuclear architecture during embryonic development, with the aim of employing them for directed differentiation of adult stem cells. These studies must be integrated from the beginning with research on the differentiation potential of adult pluripotent progenitor cells, the most plastic type of adult stem cells with great therapeutic potential.
This requires the strengthening of four key research areas:
A comprehensive analysis of the epigenetic mechanisms of gene regulation in animal development and cell fate specification. Emphasis is laid on the interconnectedness of these mechanisms at all levels from DNA methylation to chromatin modifications to cell type specific features of the nuclear architecture.
Identifying cis- and trans-regulatory key molecules (both proteinaceous transcription factors and small RNA factors) involved in regulatory networks of gene expression and silencing.
Directed regeneration of cell types required for cell replacement therapy from ‘multipotent adult precursor cells’ (MAPCs).
Novel strategies for the transdifferentiation of cell types for therapeutic purposes.