Understanding the control of cell metabolism and growth in Saccharomyces cerevisiae through manipulation of purine nucleotide concentrations

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All cells require energy to survive and to grow. Green plants get this energy from the sun and convert it into biochemicals. The cells of most other organisms, including ourselves, get their energy from nutrients (biochemicals). However, the energy requirements of a cell vary, as does the supply of the nutrients that provide that energy. For instance, rapidly growing cells consume significantly more energy than cells that have stopped growing, and cells supplied with a high level of nutrients have more energy available for use than those kept on a starvation diet. Therefore, cells need control systems capable of both sensing the quantity and quality of nutrients available, and ensuring that the chemical processes which generate and consume energy are always balanced properly. What we don't understand is what it is that cells monitor to perform this balancing act. We have some clues that they record the amount or ratio of two families of high-energy biochemicals. Thus these biochemicals act not just as sources of energy but also as signals of nutrient status. We aim to investigate their role in the nutrient control systems using cells of the brewing and baking yeast, Saccharomyces cerevisiae. The structure and ways of working of yeast cells are pretty much the same as those of human cells. This means that what we learn about yeast provides important information about how our own cells, and those of our farm animals and crop plants, work. This can help us to understand how cells malfunction to produce disease. One of the primary characteristics of tumour cells, for instance, is that they grow and divide much more rapidly than a normal healthy cell of the same tissue type. Moreover, the energy metabolism of tumour cells is different from that of normal cells; in fact, it is more like that of yeast.This project is not only important for our understanding of disease. Yeast is also increasingly used as a living factory for the sustainable production of renewable/carbon-neutral energy sources, and of biochemicals of pharmaceutical importance. Biotechnologists are introducing new metabolic pathways into yeast for the production of fuels or chemicals. This hijacks yeast metabolism away from its normal processes, and requires it to use its energy resources in a significantly different way. Additional burdens on metabolism may also arise as a result of nutrients being supplied to the yeast, to convert into these useful products, that are very different from its normal diet. This would typically be the case in commercial biotechnology processes where cheap waste materials, from forestry, agriculture, or the food industry are employed. A detailed understanding of the mechanisms which control and balance the supply and use of energy in yeast cells will help us increase the yields and efficiencies of novel biotechnological processes like these, thereby making it more likely that they can be implemented and commercially viable.