A versatile bioreactor/fermenter system for 'omics' research on diverse aspects of microbial physiology

多功能生物反应器/发酵罐系统，用于微生物生理学各个方面的“组学”研究

• 批准号: BB/E01318X/1
• 负责人: George Salmond
• 金额: $ 8.96万
• 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: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE01318X%2F1
• 关键词: versatile; bioreactor; fermenter; system; omics

The proposed research covers multiple areas of microbial physiology. Single celled microbes such as bacteria and yeasts have to adapt rapidly to changes in their immediate environments. This adaptation capacity depends on their ability to constantly sense a multiplicity of environmental cues (such as temperature, nutritional status, oxygen availability, fluctuations in acidity and alkalinity, and the presence of small molecules that are made by other microbes). Bacteria can use small diffusible molecules as chemical signals reporting the density of bacterial populations (self and competitors). This information can be used to change the adaptive responses of the microbes such that they make new products that might be appropriate to that environment. For example, at high cell density bacteria may become more virulent by making toxins or enzymes that attack their host plants, animals or man. Similary, some microbes can make antibiotics that can kill their competitors and allow them to colonise or defend niches more effectively. Microbes have to respond to diverse environmental stresses - and they often have to do this rapidly as a 'life or death' response. In the genome sequences of microbes, as much as 30-40% of the genes have no predictable biological function so it is important to try to elucidate what these 'unknown' genes actually do for the microbe. Yeast cells are excellent experimental tools for such studies because their genome (genetic material) sequence is known and they are easily grown in the laboratory. Similarly, bacteria are easy to cultivate in laboratory conditions in growth media the composition of which can be easily controlled and defined. Thus, using bacteria and yeast as experimental tools, it is possible to try to understand many different aspects of microbial physiology and metabolism - in particular, how microbes adapt to environmental stresses such as nutritional fluctuations, intercellular chemical signalling and antibiotic production. To study these events in a controlled way it is essential to have apparatus that allows the reproducible growth of microbes in a totally controllable fashion, allowing the experimentalist the opportunity to define the nutrition of the microbe, its growth rate and all other environmenal parameters such as temperature and pH. The only way to achieve this reproducibly is to grow the microbes in a fermenter (bioreactor) that allows total growth control. Only then can experiments be done on the genetics, biochemistry, physiology and metabolism of the microbes to generate robust and reproducible results from which it is possible to deduce how the biology of microbes dictates their responses to their environment. This proposal, therefore, is aimed at securing funds for a simple and flexible fermenter system that can be accessed by five (at least) different research groups in the Department of Biochemistry who are working on a range of problems in the biology of microbes.

拟议的研究涵盖微生物生理学的多个领域。单细胞微生物，如细菌和酵母，必须迅速适应其直接环境的变化。这种适应能力取决于它们不断感知多种环境线索的能力（如温度、营养状况、氧气供应、酸碱度的波动以及其他微生物产生的小分子的存在）。细菌可以使用小的可扩散分子作为化学信号，报告细菌种群（自身和竞争对手）的密度。这些信息可以用来改变微生物的适应性反应，使它们产生可能适合该环境的新产品。例如，在高细胞密度下，细菌可能会通过制造毒素或酶来攻击宿主植物、动物或人类，从而变得更具毒性。同样，一些微生物可以制造抗生素来杀死它们的竞争对手，使它们能够更有效地定居或保卫生态位。微生物必须对不同的环境压力做出反应-而且它们通常必须迅速做出“生或死”的反应。在微生物的基因组序列中，多达30-40%的基因没有可预测的生物学功能，因此试图阐明这些“未知”基因对微生物的实际作用非常重要。酵母细胞是此类研究的极好实验工具，因为它们的基因组（遗传物质）序列是已知的，并且它们很容易在实验室中生长。类似地，细菌易于在实验室条件下在生长培养基中培养，其组成可以容易地控制和限定。因此，使用细菌和酵母作为实验工具，可以尝试了解微生物生理学和代谢的许多不同方面-特别是微生物如何适应环境压力，如营养波动，细胞间化学信号和抗生素生产。为了以受控的方式研究这些事件，必须有允许微生物以完全可控的方式可再现地生长的装置，允许实验者有机会定义微生物的营养，其生长速率和所有其他生物学参数，如温度和pH值。唯一的方法，以实现这一可重复的是培养微生物在发酵罐（生物反应器），其允许总生长控制。只有这样，才能对微生物的遗传学，生物化学，生理学和代谢进行实验，以产生可靠和可重复的结果，从中可以推断微生物的生物学如何决定它们对环境的反应。因此，该提案旨在为一个简单灵活的发酵罐系统获得资金，该系统可以由生物化学系的五个（至少）不同的研究小组访问，这些研究小组正在研究微生物生物学中的一系列问题。