Integrating metagenomics, metabolomics and strand-specific metatranscriptomics data of the human gut microbial ecosystem to predict treatment response in newly diagnosed children with inflammatory bowel disease.

• Applicant: Dr. Marie-Madlen Pust
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Medical Informatics and Medical Bioinformatics ; Microbial Ecology and Applied Microbiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530694780

The term inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory conditions that affect the entire or parts of the human gastrointestinal tract, caused by complex interactions among host, microbial, and environmental factors. The prevalence and global burden of IBD continue to rise rapidly, highlighting the importance of developing new knowledge-driven research strategies. In the proposed project, the multi-layered nature of IBD will be studied by integrating longitudinal multi-omics data layers, including metagenomics, strand-specific metatranscriptomics, and metabolomics data obtained from the gut microbial communities of hundreds of healthy children and newly diagnosed children with IBD (n > 400). Thus, in addition to the taxonomic patterns driving disease development and progression - which have been investigated in the past - the biological functionality of microbial gene regulation in terms of sense-antisense transcription and metabolite production during onset and remission of the condition will be explored for the first time. Since a dynamic multi-view graph integration approach aligns with the dynamic multi-layered nature of the condition, a neural network architecture for supervised graph classification and graph interpretation will be implemented to extract intra- and inter-layer global or local substructure features of importance. The overall objective is to identify disease-relevant sense-antisense regulatory mechanisms in complex gut microbial communities and link the relevant patterns with distinct microbial taxa as well as metabolite production and secretion obtained from stool and plasma samples. In addition to advancing the IBD microbiome research field by investigating the gut microbiome from a previously unexplored angle, I will be mentored by experts in the field who have led and published several landmark studies characterizing the human microbiome, immune function, tissue biology, and genetics of IBD patients. I will participate in a variety of training and leadership courses at Harvard University, the MIT, and the Broad Institute of MIT and Harvard, with the aim of further developing the skills required to pursue a career as an independent researcher and group leader in the German academic research environment thereafter. Consequently, the project complies with both DFG's missions to foster fundamental discoveries and knowledge-driven research strategies addressing acute research needs, as well as supporting early career scientists in developing their skill profile and scientific networks to become internationally connected future academic leaders in Germany.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Ramnik Xavier