Project Details
Projekt
Z: Metabolomics, microbial community modelling and data integration
Applicants
Dr. Silke Heinzmann; Professor Dr. Christoph Kaleta
Subject Area
Gastroenterology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426660215
In this Z project, we will provide support for metabolomics, metabolic modelling and data integration for the research unit. In terms of metabolomics, we will generate metabolomics data for the project partners applying our different non-targeted and targeted LC-MS/MS and NMR workflows. Such datasets will then be leveraged by generating spectral similarity networks of metabolomics data and corresponding metadata to visualize hidden patterns and complex interactions on subject, group and metabolite level, thus revealing novel disease features from the metabolomics data. In addition, we will pursue the crucial question of metabolic origin of detected metabolites, by implementing a data-driven and database-driven approach for classification into endogenous, dietary and microbial metabolites. Thus adding deeper knowledge to potential targets of disease-driven metabolic changes. In the context of metabolic modelling, we will provide support in terms of metabolic network reconstruction, constraint-based modelling and data integration to identify specific metabolic pathways through which the microbiome influences inflammatory processes in the host. To this end, we will in-depth characterize individual metabolic pathways through which the microbiome influences disease processes in the host that we have pinpointed in the first funding phase to identify the specific metabolites through which the interaction is mediated. We will integrate different types of OMICs data generated by partners in the research unit and recently established knowledge about novel pathways through which the microbiome influences the host. Moreover, we will specifically investigate whether these pathways are universal features of inflammatory processes across all patients or whether there is patient-specific heterogeneity, especially also in pre-disease phases. We will subsequently leverage this knowledge to identify specific interventions that counteract disease-driving changes in the microbiota through nutrient supplementation which will be experimentally tested in bioreactor culture. In parallel, we will provide support in the identification of suitable candidate species for minimal synthetic communities as therapeutic agents against inflammatory bowel disease. Thus, this Z project will provide essential support for this research unit by allowing to add knowledge on biochemical and physiological processes in IBD and retrace the origin of metabolic processes to endogenous changes, dietary influences, or direct microbial involvement. Moreover, it will leverage metabolic modelling to pinpoint specific metabolic pathways through which the microbiota modulates inflammation in the host and how they can be manipulated.
DFG Programme
Research Units
