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

RII Track-2 FEC：先进生物制造：通过基因组到表型组预测促进宿主发育和高质量药物的改进

基本信息

批准号：
1736123
负责人：
Sarah Harcum
金额：
$ 600万
依托单位：
Clemson University
依托单位国家：
美国
项目类别：
Cooperative Agreement
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1736123&HistoricalAwards=false
关键词：
RII Track FEC Advanced Biomanufacturing

项目摘要

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.

非技术描述这项以研究基础设施改进 Track-2 为重点的 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，以更好地了解中国仓鼠卵巢（ CHO）细胞系，用于制造大多数生物制药。例如，50%以上的生物制药采用CHO细胞制造，CHO细胞产品的全球销售额每年超过700亿美元。对基因组稳定性和表型组之间的基本联系缺乏了解，极大地限制了改进细胞系并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，该项目还将指导四名处于早期职业生涯的终身教职的少数族裔 (URM) 教员，并培训博士后学者以及研究生和本科生。该项目的愿景是创建一个来自三个 EPSCoR 管辖区的可持续、高影响力的协作研究团队，创新基础基因组-表型组知识并解决生物制药制造挑战，以：1）改善患者获得药物的机会； 2）培养一支高技能、多元化和包容性的劳动力队伍； 3) 获得适用于任何生物系统的基本基因组到表型组知识。技术说明中国仓鼠卵巢 (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重症的促红细胞生成素 (EPO)贫血。这些细胞系提供了一个独特的机会来定量解决基因组和表型组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组。该项目重点研究 CHO 细胞基因组不稳定性的基础，旨在扩大对基因组与环境之间产生可变表型的复杂相互作用的定量理解。该项目将加强学术界之间现有的合作，并为南卡罗来纳州、特拉华州和路易斯安那州四所机构的 URM 终身教职人员提供指导。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物制药的制造能力。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) 扩大和促进终身教授、早期职业生涯中代表性不足的少数族裔 (URM) 教职人员的参与； 5) 为 URM 学生提供研究经验，并在参与 EPSCoR 的辖区之间建立学生交流。