Phase I I/UCRC Johns Hopkins University Site: Advanced Mammalian Biomanufacturing Innovation Center (AMBIC)

I 期 I/UCRC 约翰霍普金斯大学基地：先进哺乳动物生物制造创新中心 (AMBIC)

• 批准号: 1624684
• 负责人: Michael Betenbaugh
• 金额: $ 75万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1624684&HistoricalAwards=false
• 关键词: Phase; UCRC; Johns; Hopkins; University

Phase I I/UCRC Johns Hopkins University Site: Advanced Mammalian Biomanufacturing Innovation Center (AMBIC).Johns Hopkins University, University of Delaware, Clemson University, and University of Massachusetts-Lowell have jointly established a multi-university, Phase I I/UCRC entitled the Advanced Mammalian Biomanufacturing Innovation Center (AMBIC). Over the past two decades, the biopharmaceutical industry has emerged as one of the major manufacturing industries and engines of growth in the US economy. Biomanufacturing represents nearly 2% of the total US GDP and its fraction is expanding. Much of biomanufacturing involves the use of cells to make medicines. Examples of these types of medicines include cancer medicines and vaccines. A key element in developing these medicines is the need to establish complex manufacturing processes. AMBIC will implement engineering innovations to enhance the capabilities of our nation to manufacture these important life-extending and life-saving medicines. Such improvements will improve the competitiveness of US biomanufacturing in coming decades leading to more economic investment by these companies and more jobs for American workers. The mission of AMBIC is to develop enabling technologies, knowledge, design tools and methods that apply and integrate high-throughput and genome-based technologies to fast-track advanced biomanufacturing processes. AMBIC is the first I/UCRC dedicated to mammalian cell culture upstream development focusing on Chinese hamster ovary (CHO) cells, the principal biopharmaceutical production host of industry. AMBIC will bring together leading academic and industrial biotechnologists focused on mammalian cell culture manufacturing at a pre-competitive research level to address the complex problems in biopharmaceutical manufacturing. This multi-university center will allow AMBIC to leverage the skills and the expertise of many faculty members across the Sites. AMBIC will be a critical catalyst towards maintaining national excellence in biopharmaceutical production by conducting research in: 1) Understanding Industrially-Relevant Biology (e.g., all -omics, bioinformatics, process and product quality, etc.); 2) Process Monitoring & Control (e.g., analytics, instrumentation, data mining and modeling); 3) Consensus and Standardization Issues (e.g., standards, simple fingerprints, raw material issues, regulatory issues, forensic bioprocessing, clonality). Through systems-level biology analysis, novel cell line development, bioreactor optimization, and advanced analytics, AMBIC will provide transformative solutions that can lower biomanufacturing costs and improve bioprocessing efficiency. Most importantly, these advances may ultimately serve to make more biopharmaceuticals available to patients that need them and lower overall health care costs for consumers. In addition, AMBIC will establish and maintain a pipeline of educated and motivated students at multiple levels for careers in biopharmaceutical manufacturing and development. Collaborations with corporate partners will enable the students to work on the most pressing problems that the industry faces. Furthermore, this center will serve to engage and excite students from under-represented minority populations to pursue a career in life sciences, engineering, or related STEM fields. An important part of the AMBIC activities and a committed goal of the PIs is to increase the participation of women and under-represented minorities in STEM disciplines by energizing students from all backgrounds about the exciting opportunities to help others through STEM careers in biotechnology and biomedicine.

I 期/UCRC 约翰·霍普金斯大学基地：先进哺乳动物生物制造创新中心 (AMBIC)。约翰·霍普金斯大学、特拉华大学、克莱姆森大学和马萨诸塞大学洛厄尔分校联合建立了一个多大学 I/UCRC 项目，名为先进哺乳动物生物制造创新中心 (AMBIC)。 过去二十年来，生物制药行业已成为美国主要制造业和经济增长引擎之一。 生物制造占美国 GDP 总量的近 2%，而且这一比例正在扩大。许多生物制造涉及使用细胞来制造药物。 这些类型的药物的例子包括癌症药物和疫苗。开发这些药物的一个关键因素是需要建立复杂的制造工艺。 AMBIC 将实施工程创新，以增强我国生产这些重要的延长生命和挽救生命的药物的能力。 这些改进将提高美国生物制造在未来几十年的竞争力，从而为这些公司带来更多的经济投资，并为美国工人提供更多的就业机会。 AMBIC 的使命是开发应用和集成高通量和基于基因组的技术的支持技术、知识、设计工具和方法，以快速跟踪先进的生物制造工艺。 AMBIC 是第一个致力于哺乳动物细胞培养上游开发的 I/UCRC，重点关注中国仓鼠卵巢 (CHO) 细胞，这是行业主要的生物制药生产宿主。 AMBIC 将汇集领先的学术和工业生物技术专家，专注于竞争前研究水平的哺乳动物细胞培养制造，以解决生物制药制造中的复杂问题。 这个多大学中心将使 AMBIC 能够利用各个站点许多教员的技能和专业知识。 AMBIC 将通过开展以下研究来成为保持国家生物制药生产卓越性的关键催化剂： 1) 了解工业相关生物学（例如，全组学、生物信息学、工艺和产品质量等）； 2) 过程监控（例如分析、仪器仪表、数据挖掘和建模）； 3) 共识和标准化问题（例如标准、简单指纹、原材料问题、监管问题、法医生物处理、克隆性）。 通过系统级生物学分析、新型细胞系开发、生物反应器优化和高级分析，AMBIC 将提供能够降低生物制造成本并提高生物加工效率的变革性解决方案。 最重要的是，这些进步最终可能有助于为有需要的患者提供更多的生物药品，并降低消费者的总体医疗保健成本。 此外，AMBIC 将建立并维持一个受过教育、积极进取的多层次学生管道，以从事生物制药制造和开发职业。 与企业合作伙伴的合作将使学生能够解决行业面临的最紧迫的问题。 此外，该中心还将吸引和激励少数族裔学生在生命科学、工程或相关 STEM 领域从事职业。 AMBIC 活动的一个重要组成部分和 PI 的坚定目标是通过激励来自不同背景的学生了解通过生物技术和生物医学领域的 STEM 职业帮助他人的令人兴奋的机会，从而增加女性和代表性不足的少数群体对 STEM 学科的参与。

项目成果

Reconstruction of reverse transsulfuration pathway enables cysteine biosynthesis and enhances resilience to oxidative stress in Chinese Hamster Ovary cells

逆转硫途径的重建使中国仓鼠卵巢细胞能够进行半胱氨酸生物合成并增强对氧化应激的抵抗力

• DOI: 10.1016/j.ymben.2023.02.010
• 发表时间: 2023
• 期刊: Metabolic Engineering
• 影响因子: 8.4
• 作者: Chen, Yiqun;Betenbaugh, Michael J.
• 通讯作者: Betenbaugh, Michael J.

Chemical inhibitors of hexokinase‐2 enzyme reduce lactate accumulation, alter glycosylation processing, and produce altered glycoforms in CHO cell cultures

• DOI: 10.1002/bit.28417
• 发表时间: 2023-05
• 期刊: Biotechnology and Bioengineering
• 影响因子: 3.8
• 作者: Harnish Mukesh Naik;Swetha Kumar;J. Reddy;Jacqueline E. Gonzalez;Brian O. McConnell;Venkata Gayatri Dhara;Tiexin Wang;Marcella Yu;M. Antoniewicz;M. Betenbaugh