Molecular sensors for nutrients metabolites and messengers: tools for understanding the regulation of the metabolome
All organisms depend on the supply with nutrients. However the supply may change, thus the cells have to acclimate to changes in supply. To prevent damage by excess or due to starvation, homeostatic mechanisms have evolved. Regulatory networks coupled to primary sensors/receptors play a crucial role in homeostatic control.
In order to understand these networks, the first task is to identify the crucial components that are regulated. While cellular uptake, biosynthesis and release from internal stores (either from polymers such as strach or from internal compartments) can lead to increased levels, export, metabolism, and compartmentation act as negative components on the steady state level. Each of these steps may be regulated to control homeostasis in a changing environment. Many of the players have been identified, such as plasma membrane glucose, sucrose and amino acid transporters mediating uptake into the cytosol, as well as many of the enzymes that modify/synthesize/degrade the nutrient. In contrast, still little is known about cellular export and compartmentation. New tools seem necessary to identify the respective genes/proteins since export and compartmentation are technically difficult to measure in a living organism. Moreover, little is known regarding the mechanisms that keep nutrients in check, since it has been difficult to measure steady state levels with subcellular and high temporal resolution. Genetic approaches have provided some insights, and systems approaches promise to help us understand large parts of the metabolic and regulatory networks. To address these important gaps, new tools are required as well: tools for high throughput genetic manipulation, such as the yeast knock-out collection or systematic siRNA combined with the tools that allow quantitative and dynamic monitoring of steady state nutrient levels with subcellular resolution. A better understanding of these networks may provide promising new ways to improve metabolism in fungi and plants and to cure metabolic defects.
Major goals of the team are:
to clone the missing components such as exporters, transporters for compartmentation and regulators, and
to identify the signaling networks controlling homeostasis.
Our projects focus on carbon and nitrogen signaling and we use a comparative approach by using three model systems: yeast, Arabidopsis and mammalian cells. We developed new tools to study homeostasis, namely genetically encoded FRET sensors for sugars and amino acids. Complementary to the analysis of the signaling networks is an approach to systematically map membrane protein interactions to identify the underlying physical networks.