Seminars

Cells, both eukaryotic and prokaryotic ones display "metabolic behaviours". In particular, they are able to alter their metabolic fluxes in response to environmental - or internal - clues. One of the most well-studied metabolic behaviours is the switch from respiration to respire-fermentation, with increasing growth rate. How do cells achieve this switch? What regulates it and how can it be modulated? Existing modelling approaches currently are not able to fully answer such questions.
Here, I will share our ongoing modelling and experimental work towards answering these questions. I will introduce our modelling approach, which focusses on metabolic branch points and the involvement of reactions with co-substrates (such as ATP, NADH, etc.) around them.
Using such models, we found that co-substrate dynamics can cause a flux switch at the branch point, with increasing incoming flux. We call this a "built-in regulation through co-substrate dynamics". Applying this theory to yeast pruvate branch point, we found that the resulting models show NADH dynamics "driving" the metabolic overflow switch, i.e. onset of respiro-fermentation. Furthermore, the models predict alterations of NADH dynamics causing shifts in the glycolysis rate required for respiro-fermentation onset.
I will finish the talk by explaining our ongoing experimental studies on baker's yeast, where we combine culture and single-cell measurements. With these measurements, we are aiming to quantify NADH dynamics during onset of respire-fermentation, and provide experimental support for our theories.