Regulating the supply (catabolism) and demand (anabolism) of energy in eukaryotic systems is one of the most important and conserved processes in biology. While a vast amount of information is available about the individual components, global structure and local regulation of energetics, relatively few detailed studies exist on the global dynamic influence of energetic state on cellular physiology. Therefore, we are investigating how growth rate, glucose feed and [ATP], [ATP]:[ADP] and energy charge influences the physiology of continuously grown bakers' yeast, using physiological, chemical and genetic approaches. In this study we used an accellerostat, where the dilution rate (growth rate) is changed continuously and oscillatory growth conditions (cells autosynchronise metabolic activity resulting in an large amplitude oscillation in [ATP]:[ADP]). We also examined the optimal amount of doxycycline for each strain. Additionally, we plan to use chemical perturbation, dynamically changing glucose feed (dstat) and a synthetic doxycycline-inducible ATP-burning circuit. It is envisaged that these studies will help unravel the complex metabolic involved in the cells response to energy availability and lead to a deeper understanding of cellular energetics eukaryotes. Thus providing invaluable insights into consequences of energetic dysregulation involved in conditions such as cancer (Warburg effect), metabolic syndrome and ageing.

研究業績
国際学会における発表
Baba C, Hesketh A, Tomita M and Murray DB., Modulation for the energetic state of continuously grown yeast by chemical and genetic approaches, Japan Q-Bio Week Tokyo Symposium, Jan 2015.