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

了解通过操纵嘌呤核苷酸浓度对酿酒酵母细胞代谢和生长的控制

基本信息

批准号：
BB/J01821X/1
负责人：
Stephen Oliver
金额：
$ 72.59万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ01821X%2F1
关键词：
Understanding control cell metabolism growth

项目摘要

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.

所有细胞都需要能量来生存和生长。绿色植物从太阳中获取能量并将其转化为生化物质。大多数其他生物的细胞，包括我们自己，从营养物质（生化物质）中获得能量。然而，细胞的能量需求是变化的，提供能量的营养物质的供应也是变化的。例如，快速生长的细胞比停止生长的细胞消耗更多的能量，并且提供高水平营养的细胞比那些保持饥饿饮食的细胞有更多的能量可供使用。因此，细胞需要控制系统，既能感知可用营养物质的数量和质量，又能确保产生和消耗能量的化学过程始终保持适当的平衡。我们不明白的是，细胞监控着什么来执行这种平衡行为。我们有一些线索，它们记录了两种高能生物化学物质的数量或比例。因此，这些生化物质不仅作为能量来源，而且作为营养状况的信号。我们的目的是调查他们的作用，在营养控制系统中使用的酿造和烘焙酵母，酿酒酵母细胞。酵母细胞的结构和工作方式与人类细胞几乎相同。这意味着我们对酵母的了解提供了关于我们自己的细胞以及我们的农场动物和作物细胞如何工作的重要信息。这可以帮助我们了解细胞是如何发生故障而产生疾病的。例如，肿瘤细胞的主要特征之一是它们的生长和分裂速度比相同组织类型的正常健康细胞快得多。此外，肿瘤细胞的能量代谢与正常细胞不同，事实上，它更像是酵母。酵母也越来越多地被用作可再生/碳中和能源和具有制药重要性的生物化学品的可持续生产的生活工厂。生物技术专家正在将新的代谢途径引入酵母中，用于生产燃料或化学品。这劫持了酵母代谢远离其正常过程，并要求它以显着不同的方式使用其能源。代谢的额外负担也可能由于营养物质被供应给酵母而产生，转化为这些有用的产品，这些产品与正常饮食非常不同。这通常是商业生物技术过程中的情况，其中使用来自林业、农业或食品工业的廉价废料。详细了解控制和平衡酵母细胞中能量供应和使用的机制将有助于我们提高这些新型生物技术过程的产量和效率，从而使它们更有可能实现和商业可行。