Dynamic regulation of cellular phenotype for bioprocess optimization

本研究计划的目标是制定更好的策略来优化和加强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工业。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工作，生物过程对环境的影响通常低于其他可能需要极端操作条件的替代过程。该程序旨在系统地调节细胞环境以提高工艺性能。最初的努力将针对经济上可行的光合作用过程的发展。**人们对利用光合细胞（特别是藻类）开发过程的兴趣日益增加，是因为它们在生产有价值产品的同时能够捕获二氧化碳。然而，光合作用过程的商业发展受到低生产率、高能量需求和高生产成本的限制。本研究将通过研究影响培养生产力的因素，确定合适的控制和优化策略，以实现具有最大生产力的健壮培养，解决与光合细胞培养系统的工程和操作相关的挑战。**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新陈代谢集中在产品积累而不是繁殖和生存上来实现的。这可以通过对细胞施加特定的环境压力来实现。例如，如果给某些藻类低氮饮食，它们会储存大量的油，这些油可以转化为柴油。然而，对细胞施加过多的压力可能会导致不良后果：细胞可能完全停止工作，或者细胞群体可能出现异质性，这往往会导致较低的生产力。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的细胞生理变化，并建立数学模型，将观察到的细胞水平变化转化为培养性能的预测。**本研究项目开发的工具将使光合作用培养物的优化和具有成本竞争力的生物燃料的生产成为可能。随着研究计划的发展，未来的研究将针对其他受到类似限制的生物过程：由于细胞异质性而缺乏可靠性，培养密度低，生产力低下。例如，生物药品的生产目前受到规模扩大过程中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，而且在低收入国家使用生物技术药物对抗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发展和商业化活动。**将对高素质人员进行技能培训，以开发和支持下一代生物工艺和生物能源项目。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、微生物回收和石油产品升级、生物修复、生物燃料、绿色化学品和食品生产。

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.