Daniëlle Gramsbergen

d.s.gramsbergen@vu.nl

How do differences in the environment translate to changes in cell metabolism? What does this do to cell physiology both instantaneously and on an evolutionary scale? Answering these questions by combining mathematical models and wet lab experiments has been of great interest to me the past few years.
My previous projects have been about modelling growth coupled production in cyanobacteria and explaining overflow metabolism in yeast combining course grained metabolic models and physiology experiments. The focus of my phD project is bringing more of this systems biology approach to mammalian cells.

For this phD project we are investigating the link between oxidative stress and NAD metabolism in human hepatic cell lines, combining kinetic metabolic models with metabolomics and cell physiology wet lab experiments. NAD is most famous for its role as redox factor, playing an important part in central carbon metabolism. However, it also serves as a substrate for enzymes involved in DNA repair and immune regulation, like sirtuins and PARPs (poly ADP-ribose polymerases). Imbalance of NAD, especially deficiency, had been linked to several pathogenic outcomes, many of them with underlying oxidative stress on cells. Administration of NAD precursors had been proposed to remedy the negative effects associated with NAD depletion, with varying success. The aim of this project is to gain a more fundamental understanding of the metabolic changes cells undergo in response to oxidative stress and investigate novel intervention strategies.