Dresden International Graduate School for Biomedicine and Bioengineering

The interest in metabolism has been revived in recent years due in part to our evolving understanding of its role in the regulation of cellular homeostasis in a variety of different models and scientific questions. This metabolically driven maintenance of cellular homeostasis is not consistent with the often assumed rigid and linear view of chemical reactions. Rather, it is a highly flexible, interconnected and responsive network that relies on extensive and highly nuanced mechanisms of regulation to direct the flow of metabolites throughout the cell.

Therefore, the general aim of our group is to understand the mechanisms of metabolic regulation in live cells in order to modulate cellular function with targeted metabolic manipulations.

Current projects

1. Metabolic Fluxes
   We use stable isotopes to the capture the dynamic nature of metabolism. The transfer of mass isotopes, such as 13C, across metabolites is highly specific, well characterized and provides a critical glimpse into the magnitude and direction of individual reactions. Our approach is built upon the previously developed MIMOSA (Mass-Isotopomer Multi-Ordinate Spectral Analysis) method, and is in continuous development as we can expand it to include other pathways or highlight specific reactions depending on the needs of each project. This approach is also used in combination with techniques of computational analysis and molecular biology to extract the most detail possible from each project.
2. Link between glucose metabolism and insulin secretion/synthesis in beta-cells
   Pancreatic beta-cells are responsible for the secretion of insulin in response to glucose stimulation and represent a major factor in managing and delaying the offset of both Type 1 and Type 2 Diabetes. Our focus here is on understanding the role of metabolism in the regulation of pancreatic beta-cell physiology. We use a combination of metabolic flux screening, computational analysis and genetic manipulation to identify metabolic targets capable of modulating insulin secretion and synthesis.
3. Role of metabolism in the regulation of stem-cell differentiation
   The transplantation of stem cell generated islets is an approach with great therapeutic potential against the progression of Diabetes. One of the Aldehyde Dehydrogenase isoforms regulates the timing of differentiation and functionality of mature islets. In this project, we aim to understand how this enzyme regulates the interaction between metabolism and the transcriptional and epigenetic machinery responsible for the differentiation program.