Mapping (epi)genome variation as a mode of disease etiology
The first comprehensive attempts to provide an epigenetic framework on a genome wide scale are now being realized en masse (e.g. NIH Roadmap). These efforts, many of which were initially performed on in vitro, have provided the seminal cataloguing system from which to organize and compare information of transcription, chromatin state and phenotypes (for example disease states). A significant body of evidence supports the existence of a robust layer of epigenetic control in the establishment of robust metabolic homeostasis mechanisms as well as in complex metabolic diseases such as obesity and diabetes. Our experimental goals intersect genetically and epigenetically founded human, mouse and fly models systems with next generation sequencing approaches to characterize the plasticity dysregulation of chromatin-based transcriptional circuitry for health and disease. Ultimately, we intersect the model organism findings with molecular analyses of clinical biopsies from highly characterized human patients, placing the findings directly into human context.
Current studies of this nature include generating reference Epigenomes for mouse and human white adipocytes from lean and obese individuals, from polycomb mutant (de-differentiating) pancreatic beta-cells, and in the fruit fly, where we are mechanistically dissecting how physiological changes in a parent can have life-long impacts on the health and rigor of offspring. These projects are funded by the Max Planck Society, the ERC, as well as individual and consortia grants from the DFG (Neuromac/eCLASH); and BMBF (DEEP/EpiTriO) funded Epigenome contributions to the International Human Epigenome Consortium (IHEC). The long-term goals thus include building up an international resource for understanding the interplay between genetics, epigenetics, gene expression, and phenotypic variation as an underpinning of disease.