RII Track-2 FEC: Advanced Biomanufacturing: Catalyzing Improved Host Development and High Quality Medicines through Genome to Phenome Predictions

这项研究基础设施改善Track-2重点EPSCoR合作（RII Track-2 FEC）奖汇集了克莱姆森大学、特拉华大学、杜兰大学和特拉华州立大学，共同开发新的生物学方法，以更好地了解用于制造大多数生物制药的中国仓鼠卵巢（CHO）细胞系。例如，超过50%的生物药品都是由CHO细胞制造的，CHO细胞的产品每年在全球的销售额超过700亿美元。缺乏对基因组稳定性和表型之间的基本联系的理解，极大地限制了改善细胞系和最终提高产品产量的能力。该项目将提供将基因组（染色体或DNA中的内容）与观察到的内容（现象组）联系起来的基础知识。该奖项为具有互补专业知识的研究人员提供了在开发生物制造知识之前进行合作的机会。此外，该项目将指导四名早期职业生涯中未被充分代表的少数民族（URM）教师，并培养博士后学者、研究生和本科生。这个项目吗?我们的愿景是在EPSCoR的三个司法管辖区建立一个可持续的、高影响力的合作研究团队，创新基本的基因组-表型学知识，解决生物制药制造方面的挑战，以实现以下目标：1)改善患者获得药物的途径；2)发展一支高技能、多样化和包容性的劳动力队伍；3)掌握适用于任何生物系统的基本基因组和表型知识。技术描述中国仓鼠卵巢（CHO）细胞是最广泛用于制造生物制药的哺乳动物宿主细胞系，包括治疗克罗恩病的英夫利昔单抗和治疗严重贫血的促红细胞生成素（EPO）。这些细胞系提供了一个独特的机会来定量地解决基因组和表型之间复杂的相互作用，因为这些细胞可以在非常严格控制的环境（生物反应器）中培养，以产生由于基因组不稳定而产生的可变表型。该项目侧重于研究CHO细胞基因组不稳定性的基础，旨在扩大对基因组与产生可变表型的环境之间复杂相互作用的定量理解。该项目将加强学术界之间的现有合作，并为位于南卡罗来纳州、特拉华州和路易斯安那州的四所大学的URM终身教职员工提供指导。这些研究人员将共同开发系统生物学方法来理解和重新设计基因组-表型关系，并应用这些知识来提高生产生物制药的能力。该项目将：1)扩大参与机构的研究基础设施；2)培养研究生在基因组-表型学知识和CHO细胞培养与工程方面的个人和集体能力；3)共享可适用于任何其他生物体的基因组-表型知识和工具，无论其是否存在基因组稳定性问题；4)扩大和促进早期职业生涯中未被充分代表的少数族裔（URM）教师的参与；5)为澳门大学的学生提供研究经验，并在参与的EPSCoR管辖区之间建立学生交流。

Non-technical descriptionThis Research Infrastructure Improvement Track-2 Focused EPSCoR Collaborations (RII Track-2 FEC) award brings together Clemson University, University of Delaware, Tulane University, and Delaware State University to develop new biological approaches to better understand the Chinese hamster ovary (CHO) cell line, which is used to manufacture most biopharmaceuticals. For example, CHO cells are used to manufacture more than 50% of biopharmaceuticals, and products from CHO cells have global sales over $70 billion per year. A lack of understanding of the fundamental link between genome stability and the phenome significantly limits the ability to improve cell lines and ultimately increase product yields. This project will provide foundational knowledge linking the genome (what is in the chromosome or DNA) to what is observed (the phenome). This award provides the opportunity for investigators with complementary expertise to collaborate in advance of developing bio-manufacturing knowledge. Additionally, this project will mentor four early-career tenure-track underrepresented minority (URM) faculty and train postdoctoral scholars and graduate and undergraduate students. The project?s vision is to create a sustainable, high impact, collaborative research team from three EPSCoR jurisdictions that innovates fundamental genome-phenome knowledge and solves biopharmaceutical manufacturing challenges to: 1) improve patient access to medicines; 2) develop a highly skilled, diverse, and inclusive workforce; and 3) acquire fundamental genome to phenome knowledge applicable to any biological system.Technical descriptionChinese hamster ovary (CHO) cells are the most widely used mammalian host cell line to manufacture biopharmaceuticals, including infliximab to treat Crohn's disease and erythropoietin (EPO) to treat severe anemia. These cell lines provide a unique opportunity to quantitatively address the complex interactions between the genome and phenome because these cells can be cultured in very tightly controlled environments (bioreactors) to generate variable phenomes due to genome instability. This project focuses on studying the basis for genomic instability in CHO cells and aims to expand the quantitative understanding of the complex interactions between the genome and environment that generates the variable phenotypes. This project will strengthen existing collaborations among academics and provide mentoring for URM tenure-track faculty members at four institutions in South Carolina, Delaware, and Louisiana. Together, these researchers will develop systems biology approaches to understand and re-engineer the genome-phenome relationship and apply this knowledge to advance the ability to manufacture biopharmaceuticals. The project will: 1) expand the research infrastructure in participating institutions; 2) build individual and collective competence graduate students in genome-phenome knowledge and CHO cell cultivation and engineering; 3) share genome-phenome knowledge and tools that could be applicable to any other organism whether or not it has issues with genome stability; 4) broaden and foster the participation of tenure-track early-career underrepresented minority (URM) faculty members; and 5) provide research experiences for URM students and establish students exchanges among the participating EPSCoR jurisdictions.