Genetics/Genomics
Systems Biology and Systems Medicine of Metabolism
Johannes Hartl
We are fascinated by the molecular processes of life and study how genetic and particularly environmental factors shape health and disease. Using mass spectrometry, we capture molecular and biochemical signatures from microbial cells to clinical samples to tackle key questions in infection biology: how host-pathogen interactions influence disease progression, microbial pathogenicity, and drug responsiveness.
Our group is associated with the Department of Biochemistry at Charité - Universitätsmedizin Berlin.
Research Focus
Background
Why do individuals vary in disease susceptibility, progression, and treatment response? Why do only a few microbes cause severe infections or develop antibiotic resistance? While genetics plays a crucial role, environmental and metabolic factors can be equally important. Our lab investigates this interplay through experimental microbiology, using clinical samples, and systems biology. We collaborate closely with clinicians and leverage advanced analytics through our association with the Ralser Lab. Specifically, we use mass spectrometry to quantify small molecules and proteins—key mediators of gene-environment interactions—at scale.
Host-Pathogen Metabolism
Fundamentally, a microbial infection is a metabolic challenge. Host and pathogen compete for nutrients to fuel growth and defense. We study microbial metabolism in the context of infections, integrating biochemical data with genetic and phenotypic diversity. By identifying the biochemical drivers of infection, we explore their impact on antibiotic efficacy and resistance evolution.
Biomarker Discovery, Pathomechanisms & Translation
Infections leave molecular signatures in blood that can inform disease diagnosis and prognosis. Using mass spectrometry, we systematically profile these biochemical fingerprints, with a particular focus on bloodstream infections. Beyond biomarker discovery, we develop computational and analytical solutions to bridge the gap between -omics research and clinical application.
Publications
C. M. Jakobson#, J. Hartl#, P. Trébulle, M. Mülleder, D. F. Jarosz, M. Ralser, A genome-to-proteome atlas charts natural variants controlling proteome diversity and forecasts their fitness effects, bioRxiv (2024). DOI: 10.1101/2024.10.18.619054 (#joint first authors)
J. Hartl, F. Kurth, K. Kappert, D. Horst, M. Mülleder, G. Hartmann, M. Ralser, Quantitative protein biomarker panels: a path to improved clinical practice through proteomics. EMBO Mol. Med. 15, e16061 (2023). DOI: 10.15252/emmm.202216061
Z. Wang, A. Cryar, O. Lemke, P. Tober-Lau, D. Ludwig, E. T. Helbig, S. Hippenstiel, L.-E. Sander, D. Blake, C. S. Lane, R. L. Sayers, C. Mueller, J. Zeiser, S. Townsend, V. Demichev, M. Mülleder, F. Kurth, E. Sirka#, J. Hartl#, M. Ralser#, A multiplex protein panel assay for severity prediction and outcome prognosis in patients with COVID-19: An observational multi-cohort study. EClinicalMedicine 49, 101495 (2022). DOI: 10.1016/j.eclinm.2022.101495 (#joint senior authors)
J. Vowinckel#, J. Hartl#, H. Marx, M. Kerick, K. Runggatscher, M. A. Keller, M. Mülleder, J. Day, M. Weber, M. Rinnerthaler, J. S. L. Yu, S. K. Aulakh, A. Lehmann, D. Mattanovich, B. Timmermann, N. Zhang, C. D. Dunn, J. I. MacRae, M. Breitenbach, M. Ralser, The metabolic growth limitations of petite cells lacking the mitochondrial genome. Nat Metab 3, 1521–1535 (2021). DOI: 10.1038/s42255-021-00477-6 (#joint first authors)
J. Hartl, P. Kiefer, A. Kaczmarczyk, M. Mittelviefhaus, F. Meyer, T. Vonderach, B. Hattendorf, U. Jenal, J. A. Vorholt, Untargeted metabolomics links glutathione to bacterial cell cycle progression. Nat Metab 2, 153–166 (2020). DOI: 10.1038/s42255-019-0166-0
