Dynamic regulation of cellular phenotype for bioprocess optimization

细胞表型的动态调节以优化生物过程

• 批准号: RGPIN-2014-06590
• 负责人: DelaHozSiegler, Hector
• 金额: $ 1.68万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=567911
• 关键词: Dynamic; regulation; cellular; phenotype; bioprocess

The goal of this research program is to develop better strategies for optimizing and intensifying whole-cell-based bioprocesses in order to foster an economically viable and sustainable bioprocessing industry. Bioprocesses are a key element for achieving a sustainable society. Living cells can produce a wide range of products, from pharmaceuticals to chemical commodities to biofuels. As living cells operate at ambient conditions, the environmental impact of bioprocesses is usually lower than other alternative processes that might need extreme operating conditions. This program aims at systematically regulating the cells environment to improve process performance. Initial efforts will target the development of economically viable photosynthetic processes. The increased interest on the development of processes using photosynthetic cells, particularly algae, is due to their ability to capture carbon dioxide while producing valuable products. The commercial development of photosynthetic processes, however, is limited by low productivity, high energy requirements, and elevated production costs. This research will address the challenges related to the engineering and operation of photosynthetic cell cultivation systems, by investigating the factors affecting culture productivity and determining suitable control and optimization strategies to achieve robust cultures with maximum productivity. Production of biofuels in algae and other photosynthetic cells is achieved by forcing the cells to focus their metabolism in product accumulation rather than reproduction and survival. This is possible by applying specific environmental stresses to the cells. For example, if a low nitrogen diet is given to certain algal strains they will store large amounts of oil that can be converted into diesel. Stressing the cells too much, however, can result in undesirable consequences: cells might completely stop working or heterogeneity in the cell population might occur, which tends to result in a lower productivity. Studying the effect of environmental factors on culture productivity requires the development of suitable automatic methods for monitoring the changes in cell physiology at the individual cell-level, and the construction of mathematical models to translate the observed cell-level changes into predictions of culture performance. The tools developed in this research program will enable the optimization of photosynthetic cultures and the production of cost-competitive biofuels. As the research program evolves, future research will target other bioprocesses that are hindered by similar constraints: lack of reliability due to cell heterogeneity, low culture densities, and meager productivities. For example, production of biopharmaceuticals is currently affected by very high costs and low reliability during scale up. As a result, the sustainability of health care systems is being threatened and there are limited possibilities for using biotech drugs to fight devastating diseases in low-income countries. A more reliable and cost-effective production of biopharmaceuticals will facilitate development and commercialization activities in those fields. Highly qualified personnel will be trained with the skills to develop and support the next generation of bioprocesses and bioenergy projects. Trained personnel will be capable of applying their skills and knowledge to different industries including biopharmaceuticals, microbiological recovery and upgrading of petroleum products, bioremediation, biofuels, green chemicals, and food production.

该研究计划的目标是制定更好的策略，优化和强化基于全细胞的生物过程，以促进经济上可行和可持续的生物加工行业。生物过程是实现可持续社会的关键要素。活细胞可以生产各种各样的产品，从药品到化学商品再到生物燃料。由于活细胞在环境条件下运行，生物工艺对环境的影响通常低于可能需要极端操作条件的其他替代工艺。该计划旨在系统地调节细胞环境，以提高工艺性能。初期的努力将以发展经济上可行的光合作用过程为目标。对使用光合细胞（特别是藻类）的过程的开发的增加的兴趣是由于它们在产生有价值的产品的同时捕获二氧化碳的能力。然而，光合过程的商业开发受到低生产率、高能量需求和高生产成本的限制。这项研究将解决与光合细胞培养系统的工程和操作相关的挑战，通过调查影响培养生产力的因素，并确定合适的控制和优化策略，以实现具有最大生产力的强大培养。在藻类和其他光合细胞中生产生物燃料是通过迫使细胞将其代谢集中在产品积累而不是繁殖和生存来实现的。这可以通过对细胞施加特定的环境压力来实现。例如，如果给予某些藻类菌株低氮饮食，它们将储存大量可转化为柴油的油。然而，对细胞施加过多的压力可能会导致不希望的后果：细胞可能完全停止工作，或者可能发生细胞群的异质性，这往往会导致生产率降低。研究环境因素对培养生产力的影响需要开发合适的自动方法来监测单个细胞水平上的细胞生理学变化，并构建数学模型将观察到的细胞水平变化转化为对培养性能的预测。该研究计划开发的工具将能够优化光合培养物和生产具有成本竞争力的生物燃料。随着研究计划的发展，未来的研究将针对受到类似限制的其他生物过程：由于细胞异质性，低培养密度和生产力低下而缺乏可靠性。例如，生物制药的生产目前受到规模扩大期间非常高的成本和低可靠性的影响。因此，卫生保健系统的可持续性受到威胁，低收入国家使用生物技术药物防治毁灭性疾病的可能性有限。更可靠和更具成本效益的生物药品生产将促进这些领域的开发和商业化活动。高素质的人员将接受培训，掌握开发和支持下一代生物工艺和生物能源项目的技能。经过培训的人员将能够将他们的技能和知识应用于不同的行业，包括生物制药、石油产品的微生物回收和升级、生物修复、生物燃料、绿色化学品和食品生产。