AG Systems Biology and Translation in Psychiatry

Advances in high throughput techniques have led to an increasing wealth of biological data, facilitating the description of human biology in health and disease in unprecedented detail. At the same time, the wealth of Omics data challenges our ways to treat, analyse, interpret, and translate data and insights into the clinical setting. The AG Systems Biology and Translation in Psychiatry works on new overarching analysis paradigms integrating deterministic modelling approaches with population statistics for translating insights from Omics data into clinical practice in the realm of neuropsychiatric diseases. Currently, we are working on three levels of systems biological modelling.

Microbiome Modelling

The microbiome contributes crucially to human health and disease through its metabolic activity. We develop theoretical concepts allowing for the population statistics treatment of constraint-based community models and apply them to clinical data, enabling the functional characterisation of the microbiome in detail. Statistical analyses of personalised constraint-based community models additionally allow for novel insights into microbial ecology.

Integrative Whole Body Modelling

Based on the Virtual Metabolic Human database, Thiele et al. (2020) developed comprehensive organ-resolved, sex-specific whole body models, translating over 80000 metabolic reactions, human physiology, and the human microbiome into one mathematical formalism that enables personalised interrogation of metabolic phenotypes. It was successful in predicting known inborn errors of human metabolism and novel gene-metabolite associations discovered by genome wide association studies. We now explore the utility of whole body models for understanding the metabolic component of neurodegenerative diseases such as Alzheimer’s disease or Parkinson’s disease.

Cohort-based metabolic modelling of stress-related disorders and brain-aging

We develop methods to facilitate in silico modelling of large cohort data, aiming to generate virtual twins of the Study of Health in Pomerania and patient cohorts from the GANI_MED project via the utilisation of personalised whole body models. Model parameters can then be utilized for predicting health outcomes and investigation of risk factors and etiological conditions for stress-related disorders and processes of brain-aging.

Ongoing collaborations of the AG Systems Biology and Translation in Psychiatry

• Prof. Ines Thiele | Molecular Systems Physiology Group, National University of Ireland, Galway, Ireland
• Prof. Anna Köttgen | Institute of Genetic Epidemiology, University Medicine Freiburg, Freiburg, Germany
• Prof. Almut Heinken | Université de Lorraine, Nancy, Francy
• Prof. Jesus Simal-Gandara | University of Vigo, Spain
• Prof. Tanya Alderete | John Hopkins University, US
• DZNE | German Center for Neurodegenerative Diseases, Partner Site Greifswald/Rostock, Rostock, Germany

Third party projects

2026-2027        Principal investigator together with Prof. Alderete (John Hopkins University, US): “Host-microbiome ecology in the face of environmental exposures“ (Night Science Programme, Volkswagen Foundation, Germany)  

2023-2027        Principal investigator in the Collaborative Research Center (SFB 1597, 1^st funding period) “Small data”, sub-project together with Prof. Köttgen (University Medicine Freiburg)”Reciprocal transfer of knowledge from population-based genetic screens to whole-body, organ-resolved models of human metabolism (B06)”, (DFG, Germany)  

2022-2025        Principal investigator together with Dr. Frost (University Medicine Greifswald) “Modelling the influence of the gut microbiome on patterns of brain aging in the general population by combining constraint-based modelling approaches with large cohort magnetic resonance imaging data.” (DFG, Germany)

2022-2025        Co-Founder of the project group “Diversity and Resilience in Complex Systems, Academy of the Sciences in Hamburg, Germany; together with Dr. Dienelt, University of Hamburg, and Dr. Gengnagel (University of Flensburg)

2022-2024        Principal investigator together with Prof. Cohen, Columbia University, US; Prof. Gurven, University of California-Santa Barbara, US; Prof. Lemoine, University of Bordeaux, France; Prof. Fülöp, University of Sherbrooke, Canada: Towards a universal characterization of human aging 1: Immunosenescence (IMPETUS foundation, US) 

Key Publications

Klier, K., Mehrjerd, A., Fässler, D., Franck, M., Weihs, A., Budde, K., Bahls, M., Frost, F., Henning, A.-K., Heinken, A., Völzke, H., Dörr, M., Nauck, M., Grabe, H.J., Friedrich, N., Hertel, J., 2025. Integrating population-based metabolomics with computational microbiome modelling identifies methanol as a urinary biomarker for protective diet–microbiome–host interactions. Food Funct. 16, 7067–7081. https://doi.org/10.1039/D5FO00761E

Franck, M., Tanner, K.T., Tennyson, R.L., Daunizeau, C., Ferrucci, L., Bandinelli, S., Trumble, B.C., Kaplan, H.S., Aronoff, J.E., Stieglitz, J., Kraft, T.S., Lea, A.J., Venkataraman, V.V., Wallace, I.J., Lim, Y.A.L., Ng, K.S., Yeong, J.P.S., Ho, R., Lim, X., Mehrjerd, A., Charalambous, E.G., Aiello, A.E., Pawelec, G., Franceschi, C., Hertel, J., Fülöp, T., Lemoine, M., Gurven, M., Cohen, A.A., 2025. Nonuniversality of inflammaging across human populations. Nat Aging. https://doi.org/10.1038/s43587-025-00888-0

Fässler, D., Heinken, A., Hertel, J., 2025. Characterising functional redundancy in microbiome communities via relative entropy. Computational and Structural Biotechnology Journal 27, 1482–1497. https://doi.org/10.1016/j.csbj.2025.03.012

Scherer, N., Fässler, D., Borisov, O., Cheng, Y., Schlosser, P., Wuttke, M., Haug, S., Li, Y., Telkämper, F., Patil, S., Meiselbach, H., Wong, C., Berger, U., Sekula, P., Hoppmann, A., Schultheiss, U.T., Mozaffari, S., Xi, Y., Graham, R., Schmidts, M., Köttgen, M., Oefner, P.J., Knauf, F., Eckardt, K.-U., Grünert, S.C., Estrada, K., Thiele, I., Hertel, J.*, Köttgen, A.*, 2025. Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits. Nat Genet 57, 193–205. https://doi.org/10.1038/s41588-024-01965-7

Basile, A., Heinken, A., Hertel, J., Smarr, L., Li, W., Treu, L., Valle, G., Campanaro, S., Thiele, I., 2023. Longitudinal flux balance analyses of a patient with episodic colonic inflammation reveals microbiome metabolic dynamics. Gut Microbes 15, 2226921. https://doi.org/10.1080/19490976.2023.2226921

Hertel, J., Heinken, A., Fässler, D., Thiele, I., 2023. Causal inference on microbiome-metabolome relations in observational host-microbiome data via in silico in vivo association pattern analyses. Cell Reports Methods 3, 100615. https://doi.org/10.1016/j.crmeth.2023.100615

Heinken, A., Hertel, J., Acharya, G., Ravcheev, D.A., Nyga, M., Okpala, O.E., Hogan, M., Magnúsdóttir, S., Martinelli, F., Nap, B., Preciat, G., Edirisinghe, J.N., Henry, C.S., Fleming, R.M.T., Thiele, I., 2023. Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine. Nat Biotechnol 41, 1320–1331. https://doi.org/10.1038/s41587-022-01628-0

Hertel, J., Heinken, A., Martinelli, F., Thiele, I., 2021. Integration of constraint-based modeling with fecal metabolomics reveals large deleterious effects of Fusobacterium spp. on community butyrate production. Gut Microbes 13, 1915673. https://doi.org/10.1080/19490976.2021.1915673

*Authors contributed equally

Full publication list: Google scholar

Prof. Dr. Johannes Hertel

johannes.hertel@med.uni-greifswald.de

Tel.: +49 (0) 3834 86 6907

Professor (W1) in Systems Biology and Translation in Psychiatry

Department of Psychiatry and Psychotherapy

University Medicine Greifswald

Ellernholzstr. 1-2

17489 Greifswald, Germany