A Platform for the CHO Biomanufacturing Systems Biology Community

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The award, funded by the Systems and Synthetic Biology Program in MCB and the Biotechnology, Biochemical and Biomass Engineering Program in CBET will provide tools and infrastructure needed to help in the biomanufacturing of protein-based high value products that can be used in a variety of applications, including as medicines. A majority of these proteins are manufactured using "mammalian cells" and represents more than $60,000,000,000 per year in sales. There are numerous problems and issues in the biomanufacturing of these proteins that have not been adequately addressed because of incomplete knowledge of how the most common cell platform technology (known as the Chinese hamster ovary or CHO cell) functions. Recently, the genome of the CHO cell has been published and shared and an international community of academic and industrial partners has emerged to organize and build upon this new knowledge. The work that will be pursued during this project will provide necessary tools and infrastructure to support the CHO genome effort, lead to a better understanding of some of the causes for problems in the biomanufacturing of proteins, and has the potential to substantially reduce the manufacturing cost of some of the most expensive biologics. Besides its importance for the research and manufacturing in the biotechnology industry, the project will also involve training of the workforce for this rapidly expanding sector of the US economy.Technical description: The establishment of the CHO K1 (a cell line) genome, together with two different versions of the Chinese hamster, offers the possibility of establishing a new reference genome and a number of related resources for this community. In Aim 1, the project will test different approaches to merge the two existing Chinese hamster genomes using a variety of bioinformatic approaches. This effort will create a new reference genome that benefits from the chromosomal information contained in one of the genomes with the high coverage depth in the other of the Chinese hamster genomes. In Aim 2, the project will develop and share bioinformatic tools related to mRNA and peptide/protein expression that should provide enhanced functionality to the current CHO genome browser. Aim 2 will also provide a resource for establishing product quality limits by offering a framework for calculating the range of possible glycoforms available to any given CHO cell. In Aim 3, the project will, for the first time, establish a framework to define genome and chromosomal (in)stability which forms the basis for important problems in biomanufacturing.