Establishment, Integration and maintenance of new research units
We propose to establish two new W3 tenure track research groups as first strategic recruitments required to link the core expertise in stem cell research with research on epigenetic mechanisms in cell fate specification during development and in nuclear reprogramming. One of these groups, homed at the Biocenter, will focus on epigenetic regulation during development. The second group will be located at the BioMedical Center and will be concerned with mechanisms of programming and reprogramming during cell differentiation. The W3 salary will allow recruiting excellent researchers in a highly competitive environment. The tenure track scheme will permit to identify young talent and thus to actively contribute to their career development. The sustained existence of the positions beyond the time frame of the current CIPSM initiative is guaranteed through allocations from the innovation pool of the State of Bavaria through the LMUinnovativ programme (Munich Network of Cell Differentiation and Regeneration).
Tenure-track W3 Group for Epigenetics and Development at the Biocenter
Emphasis should be placed on the epigenetic mechanisms of gene regulation in animal development and cell fate specification. This includes the analysis of cell type-specific gene expression patterns in a well-defined model system of cell differentiation in the context of tissue and organ development. The goal of this research is to understand the mechanisms that mediate DNA methylation and connected chromatin modifications essentially involved in this development and to explore how these mechanisms act in the context of the cell type specific nuclear architecture – the epigenome - at large. Of particular interest in this context are the mechanisms involved in reprogramming of somatic nuclei in animal cloning experiments, as well as the mechanisms responsible for gene expression patterns during normal and pathological development.
Tenure–track W3 Group for ‘Cell Differentiation’ in the BioMedical Center
The tenure track professorship (W2) for epigenetic reprogramming of differentiated cells will explore novel strategies for changing cell fate for therapeutic purposes, thereby providing the essential link between epigenetic reprogramming and regenerative medicine. Tissue-specific, temporal, and spatial gene expression patterns are controlled by genetic and epigenetic mechanisms. Successful cloning of mammals by transfer of nuclei from differentiated tissues into enucleated oocytes demonstrates that these genetic and epigenetic programs are largely reversible and that cellular pluripotency can be restored. Although these experiments show enormous plasticity in nuclei from differentiated tissues, somatic cloning is a rather inefficient and unpredictable process, and a plethora of anomalies have been described in cloned embryos, fetuses, and offspring. Accumulating evidence indicates that incomplete or inappropriate epigenetic reprogramming of donor nuclei is likely to be the primary cause of failures in nuclear transfer. Various epigenetic mechanisms, including DNA methylation, imprinting, X chromosome inactivation, histone modifications, chromatin remodeling and changes in nuclear architecture may be involved in these phenomena. Nuclear transfer represents an invaluable tool to experimentally address fundamental questions related to epigenetic reprogramming. Understanding the dynamics and mechanisms underlying epigenetic control will help to solve problems inherent in nuclear transfer technology and enable many applications, including the modulation of cellular plasticity for human cell therapies.