Investigating the Mechanisms of Epigenetic Memory at the Example of the Responsiveness of Human Immune Cells to Vitamin D

Exposure to dietary molecules during adulthood creates an epigenetic memory in immune cells affecting disease risk in later years of life. Many nutritional molecules have a direct effect on the human genome and/or epigenome, since they (or their metabolites) activate transcription factors or chromatin modifiers. This process is the mechanistic basis of the discipline nutrigenomics. Thus, the daily diet of humans leads to changes in the transcriptome and epigenome of many tissues and cell types. In this way, many physiological functions of the human body, such as a well-responding immune system, are influenced by diet. Some of these effects are not only transient but may lead to persistent changes of the epigenome in many different tissues. However, the mechanistic details of this dietary programming of the epigenome are not well understood. Therefore, in this study, the investigators will study this process at the example of epigenetic programming of primary human immune cells with the micronutrient vitamin D3. They will use the approach to follow a small but sufficient number of healthy adult volunteers (based on power calculation of self-controlled longitudinal studies) individually over time while measuring per individual a large number of molecular and dynamic parameters that will be used for mechanistic modeling, instead of investigating only few parameters from a large number of participants for statistical modeling. The main hypothesis of the investigators is that nutritional components, such as vitamin D3, have a direct effect on the epigenome of the different cell types of the immune system. Using complementary in vivo, in vitro and in silico approaches, they will investigate the mechanistic basis of this dietary epigenetic programming process and how it creates memory.