Specialized iNANO Lecture: Systems Approaches to Define and Maintain Health
Martin Kussmann1,2,3 1 Molecular Biomarkers Core, Nestlé Institute of Health Sciences (NIHS), Lausanne, Switzerland. 2Faculty of Life Sciences, Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland. 3Faculty of Science, Interdisciplinary NanoScience Center (iNANO), Aarhus University (AU), Aarhus, Denmark
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The iNANO auditorium (1593-012), Gustav Wieds Vej 14, 8000 Aarhus C

Martin Kussmann1 2 31 Molecular Biomarkers Core, Nestlé Institute of Health Sciences (NIHS), Lausanne, Switzerland.2 Faculty of Life Sciences, Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland.3 Faculty of Science, Interdisciplinary NanoScience Center (iNANO), Aarhus University (AU), Aarhus, DenmarkSystems Approaches to Define and Maintain Health
Natural human cell models (iPSCs) help guide us to key metabolic phenotypes and nutritional interventions tested in human clinical studies, which are not only performed in the classical case/control- but also in the longitudinal design incorporating challenges to homeostasis. Mainly deep sequencing-based functional genomics and nuclear magnetic resonance- (NMR-) plus mass spectrometry-based proteomics/lipidomics/metabonomics as well as micronutrient analysis [4,5] are giving us the necessary holistic mechanistic insights into the host and gut microbial metabolism across life span [6-9]. Ultimately, we translate this basic science into personalized solutions at the interface between food, pharma and diagnostics [10]. In this research and operational context, we have built from scratch the Molecular Biomarkers Core with currently 21 staff operating 5 platforms that cover all omics downstream of genomics, plus micronutrients and diagnostics. Our team establishes an integrated platform combining highly versatile and flexible biomarker/mechanism discovery/validation tools like mass spectrometry [11-14] with highly sensitive, targeted diagnostics based on cooperative ELISAs. We complement this by partnering with external expertise in DNA aptamer-based screening, metabolic flux analysis, and non-invasive nanotechnology-based diagnostics. We term this “molecular phenotyping” as an in-depth complement to classical phenotyping such as body composition and blood chemistry [10]. Together with the Functional Genomics Unit, our Molecular Biomarkers Core generates the necessary systems view on metabolic trajectories of natural human cell lines, animal models and, most importantly, human subjects [10]. The emphasis lies on “trajectory” as we monitor these biological systems over time, with every entity functioning as its own case/control pair, rather than comparing a case to a control group by taking omics snapshots at a given moment in time [1]. A further, innovative angle of our research into metabolic, cognitive and intestinal health is to assess metabolic elasticity and flexibility rather than comparing systems at homeostasis: challenging biological systems repeatedly over time and monitoring their (failure of) restoration of homeostasis is giving us early insights into deviations from healthy metabolic trajectories and opens windows of preventive opportunity [1].
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