A Platform for the CHO Biomanufacturing Systems Biology Community

该奖项由MCB的系统和合成生物学项目以及CBET的生物技术、生化和生物质工程项目资助，将提供所需的工具和基础设施，以帮助基于蛋白质的高价值产品的生物制造，这些产品可用于包括药物在内的各种应用。这些蛋白质中的大多数是用“哺乳动物细胞”制造的，每年的销售额超过600亿美元。由于对最常见的细胞平台技术（称为中国仓鼠卵巢或CHO细胞）的功能了解不完全，这些蛋白质的生物制造中存在许多问题和问题，尚未得到充分解决。最近，CHO细胞的基因组已经发表并共享，一个由学术和工业合作伙伴组成的国际社区已经出现，以组织和建立这一新知识。在这个项目中进行的工作将为支持CHO基因组工作提供必要的工具和基础设施，使人们更好地了解蛋白质生物制造问题的一些原因，并有可能大幅降低一些最昂贵的生物制剂的制造成本。除了对生物技术产业的研究和制造具有重要意义外，该项目还将涉及为美国经济中这一迅速发展的部门培训劳动力。技术描述：CHO K1（一种细胞系）基因组的建立，以及两种不同版本的中国仓鼠，为该群落建立新的参考基因组和一些相关资源提供了可能性。在目标1中，该项目将测试使用各种生物信息学方法合并两种现有中国仓鼠基因组的不同方法。这项工作将创建一个新的参考基因组，该基因组受益于中国仓鼠基因组中一个基因组中包含的染色体信息，而另一个基因组的覆盖深度高。在目标2中，该项目将开发和共享与mRNA和肽/蛋白表达相关的生物信息学工具，为当前的CHO基因组浏览器提供增强的功能。Aim 2还将通过提供计算任何给定CHO细胞可用的可能糖型范围的框架，为建立产品质量限制提供资源。在目标3中，该项目将首次建立一个框架来定义基因组和染色体（In）稳定性，这是生物制造中重要问题的基础。

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.