Pandemic preparedness research and biocontainment infrastructure at The Rockefeller University

项目摘要/摘要 洛克菲勒大学是一个独特的机构：仅有70个实验室负责人，教职员工就收到了3个 过去10年的诺贝尔医学奖和过去21年的5次(加上1次化学奖)，以及 任命18名教员为HHMI调查员，29名为美国国家科学院院士。 洛克菲勒的教职员工在病毒学的基础性发现和 传染病，历史上和现在都是如此。认识到当前大流行的重要性，结束 在过去的两年里，洛克菲勒的十几个研究小组加入了专注于 大流行威胁病毒，有许多赠款支持这项工作，并有50多份同行审查的出版物 约会。洛克菲勒实验室在识别中和抗体谱方面做出了开创性的贡献 SARS-CoV-2刺突蛋白，变异对中和的影响，并表征原子- 解析抗体与刺激性蛋白的结合。总体而言，洛克菲勒实验室正在研究 甲型病毒(如辛比斯病毒、基孔肯雅病毒)、黄病毒(如黄热病、寨卡病毒、西尼罗河病毒、波瓦桑病毒) 病毒)、肝炎病毒(丙型肝炎病毒、挪威大鼠肝炎病毒)、肝炎病毒(乙肝病毒)、 正粘病毒(流感)、冠状病毒(SARS-CoV-2和其他人类冠状病毒)和逆转录病毒 包括HIV-1。许多正在研究的病毒，包括基孔肯雅热、黄热病、西尼罗河病毒、鲍瓦桑病毒、 和SARS-CoV-2被归类为风险组3(RG3)病原体，需要BSL3遏制设施和 练习。此外，洛克菲勒的一些研究包括复制和嵌合体(VSV-)的产生。 基于)病毒，其稳定性和安全性应在BSL3条件下确定，然后在较低的 生物安全控制级别。该项目旨在增强和扩展在体内的空间和支持 以及体外研究。具体目标1是增加洛克菲勒大学的BSL3能力，以满足 在现有的实验室大楼中建立一个新的BSL3设施，以满足科学需求。具体目标2是装备 并加强新设施和大学现有的BSL3/ABSL3设施。要实现 这些目标，洛克菲勒一个非常有经验的人员团队建议：建立一个新的多重- 调查员BSL3设施；在现有的单PI BSL3设施基础上增加设备；更换现有的高压锅 并在ABSL3中增加一个增量式高压灭菌器；并对ABSL3中的配套基础设施进行现代化改造。

Project Summary/Abstract Rockefeller University is a unique institution: with only 70 Heads of Laboratories, the faculty have received 3 Nobel prizes in Medicine in the last 10 years and 5 (plus 1 in chemistry) in the last 21 years, along with appointment of 18 faculty as HHMI investigators and 29 to membership in the National Academy of Sciences. Rockefeller faculty have played an outsized role in contributions to foundational discoveries in virology and infectious disease, both historically and presently. Recognizing the importance of the current pandemic, over the past two years, a dozen research groups at Rockefeller have joined the research efforts focused on pandemic threat viruses, with numerous grants supporting the work and over 50 peer-reviewed publications to date. Rockefeller labs have made seminal contributions identifying the spectrum of neutralizing antibodies to the SARS-CoV-2 spike protein, the impact of variants on neutralization, and characterizing the atomic- resolution binding of antibodies to spike protein. Collectively, Rockefeller laboratories are working on Alphaviruses (e.g., Sindbis, chikungunya viruses), Flaviviruses (e.g., yellow fever, Zika, West Nile, Powassan viruses), Hepaciviruses (hepatitis C virus, Norway rat hepacivirus), Hepadnaviruses (hepatitis B virus), Orthomyxoviruses (influenza), Coronaviruses (SARS-CoV-2 and other human coronaviruses) and retroviruses including HIV-1. Many of the viruses under study, including chikungunya, yellow fever, West Nile, Powassan, and SARS-CoV-2, are classified as Risk Group 3 (RG3) pathogens, requiring BSL3 containment facilities and practices. Moreover, some research at Rockefeller includes the generation of replicons and chimeric (VSV- based) viruses whose stability and safety should be established under BSL3 conditions prior to use at lower biosafety containment levels. This project seeks to enhance and expand space and support for both in vivo and in vitro research. Specific aim 1 is to increase the Rockefeller University’s BSL3 capacities to meet the scientific needs by establishing a new BSL3 facility in an existing laboratory building. Specific aim 2 is to equip and enhance the new facility and the BSL3/ABSL3 facilities that already exist at the University. To achieve these aims, an extremely experienced team of personnel at Rockefeller propose to: establish a new multiple- investigator BSL3 facility; add equipment to the existing single-PI BSL3 facility; replace an existing autoclave and add an incremental autoclave in the ABSL3; and modernize the supporting infrastructure in the ABSL3.