Development and Disease Group
Introduction and scope of research
The research group Developmental & Disease focuses on fundamental questions regarding the genetic origin of phenotypic variation in the context of disease and evolution. We aim to better understand the basic mechanisms how genes are regulated in a genomic context and how this translates into specific phenotypes and/or traits. Besides our long-standing interest in deciphering the cause of rare genetic diseases, we investigate basic mechanisms of gene regulation regarding 3D genomics, long-range chromatin interaction, and the function of lncRNAs. The limb has many advantages for this sort of study as it is accessible, and the developmental steps and the major genes/molecular mechanisms are known. Using this approach, we directly link gene regulation with basic developmental processes and phenotype. In our evolution studies, genomic comparisons on multiple levels are used to identify regions in the genome that confer specific phenotypic adaptations, such as the ovotestes in female moles and the development of wings in bats. We use advanced genome engineering and synthetic genomics to manipulate genomic landscapes and reconstitute parts of one species' genome in another.
Our questions, our goals
How are genes regulated, and how is this related to the 3D folding of chromatin? How do enhancers work, and how do epigenetic modifications influence their activity? And how are these processes related to phenotypic variation? Ultimately, we want to understand how sequence is translated into phenotype. Currently, this is not possible due to our lack of knowledge of how gene regulatory landscapes work and how the interplay between enhancers, promoters, 3D chromatin folding, and epigenetics functions produces the high precision of gene expression we can observe, e.g., during development. This lack of knowledge makes it almost impossible to predict the outcome of variants in the non-coding genome. The research group works in close collaboration with the Institute for Medical and Human Genetics (IMG) at the Charité – Universitätsmedizin Berlin. The IMG provides a direct clinical connection to our work and the possibility of translating the knowledge gained into clinical practice.