Dysregulation of lipid homeostasis is related to multiple major global healthcare problems today, including aging, diabetes and cardiovascular disease. It has already been shown that nutritional modulation of lipid homeostasis via direct supplementation, e.g. n-3 fatty acids, or via indirect mechanisms, e.g. dietary polyphenols, have beneficial effects on human health. There is growing evidence that ether phospholipids such as plasmalogens play a central role in mediating such beneficial effects, but the underlying mechanisms are not understood.

ETHERPATHS aims to develop systems biology tools that will facilitate studies of dietary interventions aiming to modulate lipid homeostasis. Specifically, we will develop (1) metabolic models that enable studies of gut microbial metabolism, (2) dynamic models of systemic lipid metabolism, and (3) pathway reconstruction methods for studies of tissue-specific effects of dietary interventions.

All models will be optimized in context of studies of dietary interventions and will be integrated into a sophisticated software platform. In silico strategies will be complemented by multiple experimental approaches, including (1) dietary interventions involving n-3 fatty acids and polyphenols, combined with tracer studies, in vitro, in vivo, as well as in clinical setting (2) in vitro colon model (3) in vivo germ free and and conventional models of altered lipid metabolism, specifically plasmalogen deficiency.