Dynamic regulation of cellular phenotype for bioprocess optimization

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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.