Martin Kussmann^1 2 3

¹ 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, Denmark

Systems Approaches to Define and Maintain Health

At the Nestlé Institute of Health Sciences (NIHS, 2011 to present), we take a systems biology approach to better understand the interplay between genes, diet and lifestyle [1] so that we can act upon healthy ageing and disease prevention with a focus on metabolic [2], cognitive and intestinal [3] 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].

References

1. Kussmann M, Hager J, Morine MJ, Sonderegger B, Kaput J; Frontiers Genetics 2013 (4) 205: “A systems approach to diabetes research”.
2. Rubio-Aliaga I, Silva Zolezzi I, Kussmann M; “Proteomics in the systems-level study of the metabolic syndrome”; in “A systems biology approach to study metabolic syndrome”; Springer 2013; Ed.: Oresic M, Vidal-Puig A.
3. Lopes LV, Kussmann M; Exp. Rev. Proteomics 2011 (8) 605-614: “Proteomics at the interface of psychology, gut physiology and dysfunction – an underexploited approach that deserves expansion”.
4. Nagy K, Ramos L, Courtet-Compondu MC, Braga-Lagache S, Redeuil K, Lobo B, Azpiroz F, Malagelada JR, Beaumont M, Moulin J, Acquistapache S, Sagalowicz L, Kussmann M, Santos J, Holst B, Williamson G; Eur. J. Clin. Nutr. 2012 (67) 202-206: “Double-balloon jejunal perfusion to compare absorption of vitamin E and vitamin E acetate in healthy volunteers under maldigestion conditions”.
5. Nagy N, Lobo B, Courtet-Compondu MC, Braga-Lagache S, Ramos L, Puig-Divi V, Azpiroz F, Ramón Malagelada J, Beaumont M, Moulin J, Acquistapace S, Sagalowicz L, Kussmann M, Santos J, Holst B, Williamson G; Chimia 2014 (68) 129-134: “Vitamin E and vitamin E acetate are absorbed equally from self-assembly systems under pancreas insufficiency conditions”.
6. Kussmann M, van Bladeren PJ; Frontiers Genetics 2011 (2) 21, 1-12: “The extended nutrigenomics - understanding the interplay between the genomes of food, gut microbes and human host“.
7. Martin FPJ, Moco S, Montoliu I, Collino S, Da Silva L, Rezzi S, Prieto R, Kussmann M, Inostroza J, Steenhout P; Pediatr. Res. 2013: “Impact of breast-feeding, high and low protein formula on host-gut microbial metabolism during growth of infants from overweight and obese mothers”.
8. Collino S, Martin FPJ, Karagounis L, Horcajada MN, Moco S, Franceschi C, Kussmann M, Offord E; Mech. Ageing Dev’t 2013: “Musculoskeletal system in the old age and the demand for healthy ageing biomarkers”.
9. Montoliu I, Scherer M, Beguelin FC, DaSilva L, Mari D, Salvioli S, Martin FPJ, Capri M, Bucci L, Ostan R, Garagnani P, Monti D, Biagi E, Brigidi P, Kussmann M, Rezzi S, Franceschi C, Collino S; Aging 2014 (6) 1-19: “Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity”.
10. Kussmann M, Kaput J; Appl. Transl. Genomics (ATG) 2014: „Translational Genomics“.
11. Kussmann M, Panchaud A, Affolter M; J. Proteomics 2012 (76) 3381-3559; “Understanding genome regulation and genetic diversity by mass spectrometry”.
12. Dayon L, Sonderegger B, Kussmann M; J. Proteome Res. 2012 (10) 5081-5089: “Combination of gas-phase fractionation and MS3 acquisition modes for relative protein quantification with isobaric tagging”.
13. Dayon L, Kussmann M. EuPA Open Proteomics 2013: “Proteomics of human plasma: a critical comparison of analytical workflows in terms of effort, throughput and outcome”.
14. Dayon L, Nuñez Galindo A, Corthésy J, Kussmann M; J. Proteome Res. 2014: “A comprehensive and scalable highly automated MS-based proteomic workflow for clinical biomarker discovery in human plasma.”