scholarly journals Enhancing CHO by Systems Biotechnology

2018 ◽  
Vol 13 (10) ◽  
pp. 1800488
Author(s):  
Nicole Borth ◽  
Wei-Shou Hu
Author(s):  
Yoosuf Cader

The 2005 global revenues of publicly traded biotechnology companies have grown by 18.1% to $63.1 billion (Donn, 2006). Many countries are now investing in research and development in the biotechnology industry as it is believed this 30 year-old industry is moving toward profitability. The stock value in this industry has outperformed the average stock value in many countries. In the pre-genomic era, a typical life sciences company would have marketed diagnostic kits, assays, chemicals, measuring equipment, and research products to name a few. In the genomic era, a new range of products is marketed focusing on molecular medicine. Among these new products are bioinformatics software solutions, storage systems, biotechnology systems, and solutions researching into genes and proteins, tools for analysis of genetic sequence data, integrated systems and solutions for disease research, and new drug discovery (Cader, 2004). The need for biotechnology portals is now more than justified and will be a useful information and knowledge source.


2015 ◽  
Vol 112 (39) ◽  
pp. 12181-12186 ◽  
Author(s):  
Chaoxian Bai ◽  
Yang Zhang ◽  
Xuejin Zhao ◽  
Yiling Hu ◽  
Sihai Xiang ◽  
...  

There is a great demand for precisely quantitating the expression of genes of interest in synthetic and systems biotechnology as new and fascinating insights into the genetics of streptomycetes have come to light. Here, we developed, for the first time to our knowledge, a quantitative method based on flow cytometry and a superfolder green fluorescent protein (sfGFP) at single-cell resolution in Streptomyces. Single cells of filamentous bacteria were obtained by releasing the protoplasts from the mycelium, and the dead cells could be distinguished from the viable ones by propidium iodide (PI) staining. With this sophisticated quantitative method, some 200 native or synthetic promoters and 200 ribosomal binding sites (RBSs) were characterized in a high-throughput format. Furthermore, an insulator (RiboJ) was recruited to eliminate the interference between promoters and RBSs and improve the modularity of regulatory elements. Seven synthetic promoters with gradient strength were successfully applied in a proof-of-principle approach to activate and overproduce the cryptic lycopene in a predictable manner in Streptomyces avermitilis. Our work therefore presents a quantitative strategy and universal synthetic modular regulatory elements, which will facilitate the functional optimization of gene clusters and the drug discovery process in Streptomyces.


2018 ◽  
Author(s):  
Jahir M. Gutierrez ◽  
Amir Feizi ◽  
Shangzhong Li ◽  
Thomas B. Kallehauge ◽  
Hooman Hefzi ◽  
...  

AbstractIn mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jahir M. Gutierrez ◽  
Amir Feizi ◽  
Shangzhong Li ◽  
Thomas B. Kallehauge ◽  
Hooman Hefzi ◽  
...  

AbstractIn mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster ovary cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology.


2002 ◽  
Author(s):  
J. Darabi ◽  
H. Wang

The rapidly growing applications in micro fluidic systems, biotechnology, micro chemical analysis systems, drug delivery systems, and chip-integrated cooling systems has introduced new opportunities and challenges in developing micropumps. Micropumps are one of the crucial components for moving liquids in these miniaturized systems. In this article, the focus is placed on both fundamental scientific and application specific issues. First, a brief review of the growing need for micropumps and the state of the art materials and fabrication technologies is presented. Next, the various pumping techniques, their working principle and their potential applicability to the future development of cost-effective miniature systems are discussed. Finally, selected results of an electrohydrodynamic micropump are presented.


2017 ◽  
Vol 17 (7) ◽  
Author(s):  
Richard J. Zahrl ◽  
David A. Peña ◽  
Diethard Mattanovich ◽  
Brigitte Gasser

2008 ◽  
Vol 7 (2) ◽  
pp. 95-110 ◽  
Author(s):  
P. M. O'Callaghan ◽  
D. C. James

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