Chemical biology and metabolomics
Chemical biology is an interdisciplinary research area in which chemical synthesis is used in interaction with molecular biology to solve biological issues that cannot be resolved in a simple manner with traditional molecular biological techniques. Central to the field is the development of new, chemical biological techniques that are able to answer health scientific questions. For a number of years, our priority area has been the human metabolism and its correlation with biological aging and age-related diseases. In order to identify how aging and metabolism are connected, we develop different chemical biological tools, which are subsequently used in cellular, animal or human biological studies. There are two central techniques: re-activity-based protein profiling (RBPP) and ReactELISA. The projects are carried out in collaboration with chemists, molecular biologists, medical doctors and others.
ReactELISA is a new technique in which a biotinylated probe first captures a reactive metabolite in a biological system. Subsequently, the product is purified in a streptavidin well and quantitated with an ELISA applying an adduct specific antibody. The advantage is that the unstable metabolite is captured and stabilized prior to ELISA quantitation. The simplicity makes the technique useful for high-throughput screening for drugs or genes that affect reactive metabolite levels and hence the biological aging process.
Metabolomics is the simultaneous study of all (measurable) metabolites in a biological system. Typically, NMR, GC-MS or LC-qTOF-MS are employed as analytic techniques. Each has its advantages. UPLC-qTOF-MS is probably the most sensitive and universal technique and can in a single run measure several thousand metabolic features. By comparing the level of the individual metabolites in treated cells or blood or tissue samples to matched controls, it is possible in a relatively simple way to gain an insight into how the metabolism is affected. As such, it is a very strong technique for gaining insight and forming hypotheses about how a substance/medication works or about basic disease mechanisms.
MDMA's effect on the human metabolism may in principle be uncovered with a large human intervention study or more simply by the use of retrospective data from the department's public sector consultancy. By correlating the content of MDMA in blood samples with all measurable metabolites, it is possible to achieve a direct link to the MDMA metabolites that are formed in vivo, as well as the endogenous metabolites governed by MDMA intake. Both of these can serve to clarify MDMA's impact on the human metabolism.
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Ischemic preconditioning is a unique way to activate the human body's own defence against damage caused by blood clots. Global insight into which metabolites are regulated by ischemic preconditioning can lead to an understanding of the body's own protection against damage resulting from blood clots. In collaboration with cardiologists, a number of plasma, cell and tissue samples are examined for upward and downward regulated metabolites. Central metabolites are subsequently examined in cell and animal testing to clarify the role they play in their own self-protection. Read more in the following article: