Research

All biological systems are dynamic and complex with diverse developmental and environmental signals constantly being sensed and integrated into regulatory modules that generate precise phenotypic changes. This precision occurs through the integration across multiple molecular levels including transcription factors, RNA, post-transcriptional and posttranslational regulation, and metabolic levels involving metabolites, allosteric enzyme regulation, and intra-/inter-cellular transport.

 

The glucosinolate defense metabolites within Arabidopsis thaliana are a unique model system for studying how complex dynamic signals can be integrated within an organism to create precise outcomes. A. thaliana is a key organism to study systems biology, based upon its extensive ‘omics data and tools, natural variation and mutant collections. The defense-related glucosinolates provide several unique aspects that make them a powerful system to understand how biological systems are organized.

 

First, there is already extensive knowledge of the parts involved including all biosynthetic genes, key transcription factors, RNA- and miRNA-mediated regulation, and there is proof that direct sensing of metabolites controls transcription. Several ligand-specific membrane transporters for intra- and intercellular transport are identified.

 

A key aspect of the glucosinolates is that they are rapidly quantifiable allowing us to measure with high confidence any change in the system. Additionally, using defense related secondary metabolites (compared to primary metabolites) as model metabolites has the additional advantage that their metabolism runs ‘in parallel’ to primary metabolism in the organism, so mutant phenotypes are not usually lethal.

 

Finally, the output has a key ecological role in determining the plants fitness when it is attacked by innumerable diverse biotic organisms suggesting that the system is indispensable in the field and likely under strong selective pressure.

 

Fig. 1: Schematic representation of the core aims of the Center. Objective 1: We will elucidate the dynamic interactions of pathway-specific proteins in metabolons and regulons. Objective 2: We will identify the molecular targets for RNA-mediated regulation and metabolite sensing. Objective 3: We will decipher the entire transporter complement of a given metabolite, i.e. all intra- and intercellular transporters. Objective 4: We will visualize the orchestration of GLS biosynthesis, transport and storage using advanced bioimaging.

 

An exciting research frontier and the ultimate challenge to date with many large-scale datasets available, is to assemble biological 'parts' into their interaction networks to create models of the cellular and organismal processes.

 

Our research strategy is to employ cutting-edge technologies within protein-protein interaction, RNA-proteomics, ligand-based screens, advanced live bioimaging as well as mass spectrometry visualization tools, to go to the next level of RNA/protein/metabolite interconnectivity and gain truly novel, basic knowledge about the dynamics of biological interactions in a multi-cellular organism.