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
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.