Coordinators: H. Busch (UzL), C. Kaleta (CAU), A. Traulsen (MPI)
The aim of RTF VIII is the use of computer models to elucidate which molecular processes are involved in the pathology and treatment response in inflammatory diseases. To this end, RTF VIII employs Systems Medicine approaches that build upon high-throughput multi-scale data sets covering the microbiome, genetics, transcriptomics, proteomics and metabolomics. These data sets are integrated to build comprehensive computer models of relevant tissues that can pinpoint molecular processes involved in the pathogenesis of inflammatory diseases, monitor disease progression and inform treatment decisions.
Currently, there is both a lack of methods that are able to integrate diverse high-throughput experimental data sets and only little systemic knowledge of the involvement of different organ systems in the pathogenesis of inflammatory diseases. Moreover, due to its immense complexity, the role of the microbiome as a potential driver or mere bystander in the pathology of inflammatory diseases is only poorly understood.
The aim of RTF VIII is the reconstruction of multi-scale models that combine metabolic and immunological processes involved in the pathogenesis of inflammatory diseases. We will use these models to gain a better understanding of the molecular cross-talk involved in inflammation both within the immune system as well as between the microbiome and its host. This will allow us to disentangle the complex web of interactions between the immune system, the microbiome and the host to pinpoint key molecular processes involved in the pathogenesis of inflammatory diseases. This knowledge will allow us to develop markers that enable us to monitor the course of inflammatory diseases, also during treatment, and make more informed treatment decisions.
RTF VIII will develop a unique modeling platform that combines metabolic and immunological models of host and microbiota that, for the first time, can derive mechanistic hypotheses on the involvement of the microbiome in the pathology of inflammatory diseases. Moreover, this modeling platform will integrate diverse experimental data sets covering different aspects of inflammation (transcriptome, genome, proteome, metabolome) into a coherent model, thereby facilitating the identification of the processes involved beyond these scales.
The approaches developed in RTF VIII will include patient-specific data, thereby facilitating the reconstruction of patient-specific models. These models will therefore enable the identification of patient-specific molecular processes that are deregulated in inflammation and a patient-specific monitoring of treatment response.
- RTF I: Analysis of disease-associated shifts in microbial community metabolisms
- RTF I, RTF V, RTF VI: Determination of disease-associated genetic loci through integrative models for genomic, transcriptomic and metabolomic data
- TI-1: Development of integrated computer models of microbiome and host in inflammatory diseases for the identification of potential microbiome intervention targets
- RTF II: Experimental characterization of identified key microbial species
- RTF IV, TI-2, TI-4, CD-5: Models for the identification of functional pathways from high-throughput data obtained from patients, animal models or immune cells will be iteratively experimentally validated and improved.