Animal models and related services (AMRS) core

动物模型和相关服务（AMRS）核心

• 批准号: 10793866
• 负责人: Padmini Salgame
• 金额: $ 169.88万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-18 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10793866
• 关键词: 2019-nCoV; Address; Affect; Animal Model; Antitubercular Agents; Birds; COVID-19; Chemotherapy-Oncologic Procedure; Clinical; Containment; Disease; Disease Outbreaks; Emerging Communicable Diseases; Equipment; Exhibits; Experimental Models; Ferrets; Genes; Goals; Grant; Hamsters; Human; Human Resources; Impairment; Individual; Infection; Influenza A Virus, H5N1 Subtype; Intervention Studies; Lung; Measures; Modeling; Mutation; Mycobacterium tuberculosis; Pathogenesis; Pathogenicity; Performance; Persons; Pharmaceutical Preparations; Post-Acute Sequelae of SARS-CoV-2 Infection; Probability; Public Health; Regimen; Relapse; Research; Research Personnel; Research Support; Resources; Respiratory System; SARS-CoV-2 transmission; Services; Stress; Symptoms; Testing; Therapeutic; Toxic effect; Treatment Protocols; Tuberculosis; Variant; Workforce Development; biosafety level 3 facility; biothreat; drug candidate; efficacy testing; experience; improved; in vitro activity; influenzavirus; instrumentation; lung health; mouse model; new pandemic; novel therapeutics; pandemic disease; pandemic virus; pathogen; permissiveness; pre-clinical; prevent; programs; respiratory health; respiratory pathogen; respiratory virus; response; transmission process; treatment duration; tuberculosis drugs; viral transmission

ABSTRACT Animal Models and Related Services (AMRS) Core The overall goal of Animal Models and Related Services (AMRS) Core 3 is to establish a biocontainment research support service core devoted to developing animal models of BSL3 pathogens and associated support services. Core 3 is highly relevant to the basic and translational foci of the research programs at Rutgers. No animal model perfectly reproduces the response to infection seen in humans. In Core 3, we are therefore developing different animal models that can be used to address specific aspects related to respiratory pathogen- induced disease. The newly developed animal models, and their subsequent use by RBL investigators with AMRS Core support, along with the purchase of additional specialized equipment will support and enhance the research enterprise of Rutgers investigators exploring various aspects of pathogen infection and transmission, and host disease pathogenesis. As SARS-CoV-2 transitions from a pandemic virus to an endemic one, new variants continue to appear with higher transmission rates which appear to correlate with lower pathogenicity. AIM 1 will develop animal models for investigating transmissibility of SARS-CoV-2. There have been five IAV pandemics since the 1900s, and there is ongoing concern that the current outbreak of high pathogenic H5N1 avian Influenza virus, which has affected more than 50 million birds so far, could jump to humans and cause a new pandemic. Animal models will be devloped to study IAV transmission in AIM 2. A subset of individuals has prolonged complications after COVID-19, which is known as post-acute sequalae of COVID-19 (PASC). In Aim 3, we will develop the hamster model to study PASC. The ferret respiratory tract has several similarities to humans and ferrets are highly permissive to M. tuberculosis (Mtb) and several human respiratory viruses. Therefore, we propose in Aim 4 to develop a ferret transmission model and test its suitability for investigating transmissibility of clinical strains of Mtb and in identifying the genes that Mtb requires to survive the successive stresses associated with transmission. More than half of the people with microbiologically cured tuberculosis (TB) exhibit some form of pulmonary impairment after TB (PIAT) affecting long-term respiratory health. In Aim 5, we will develop a pre-clinical mouse model of pulmonary impairment after TB (PIAT) for evaluating adjunct host directed therapeutics. Establishment of animal models to test efficacy of newly discovered compounds with anti- TB activity in vitro would significantly advance the TB drug program. In Aim 6, we will stablish a pre-clinical murine model for efficacy testing of new TB drug candidates. As each of these six aims are completed, the AMRS Core’s technical staff will then aid RBL investigators in the performance of these animal models in their own grant supported research. The personnel, instrumentation and experience acquired achieving these aims will also be harnessed to develop and support additional animal models as required to address new biothreats, pandemics or emerging infectious diseases.

摘要 动物模型和相关服务 (AMRS) 核心 动物模型和相关服务 (AMRS) 核心 3 的总体目标是建立生物防护 研究支持服务核心致力于开发 BSL3 病原体动物模型和相关支持 服务。核心 3 与罗格斯大学研究项目的基础和转化重点高度相关。不 动物模型完美地再现了人类对感染的反应。因此，在核心 3 中，我们 开发不同的动物模型，可用于解决与呼吸道病原体相关的特定问题 诱发疾病。新开发的动物模型以及 RBL 研究人员随后使用的 AMRS 核心支持以及购买额外的专用设备将支持和增强 罗格斯大学研究人员的研究企业探索病原体感染和传播的各个方面， 和宿主疾病的发病机制。随着 SARS-CoV-2 从大流行病毒转变为地方性病毒，新的 变异继续以较高的传播率出现，这似乎与较低的致病性相关。 AIM 1 将开发动物模型来研究 SARS-CoV-2 的传播性。已有 5 个 IAV 自 1900 年代以来大流行，人们持续关注当前高致病性 H5N1 的爆发 禽流感病毒迄今已感染超过 5000 万只鸟类，可能会传染给人类并导致 新的流行病。将开发动物模型来研究 AIM 2 中的 IAV 传播。一部分个体已 COVID-19 后出现长期并发症，称为 COVID-19 急性后遗症 (PASC)。瞄准 3、我们将开发仓鼠模型来研究PASC。雪貂的呼吸道与 人类和雪貂对结核分枝杆菌 (Mtb) 和几种人类呼吸道病毒高度敏感。 因此，我们在目标 4 中建议开发雪貂传播模型并测试其对于调查的适用性 结核分枝杆菌临床菌株的传播性以及鉴定结核分枝杆菌在连续的生存过程中所需的基因 与传输相关的应力。超过一半的结核病患者已通过微生物治愈 (TB) 结核病 (PIAT) 后表现出某种形式的肺损伤，影响长期呼吸系统健康。在目标 5 中， 我们将开发结核病后肺损伤的临床前小鼠模型（PIAT），用于评估辅助宿主 定向治疗。建立动物模型来测试新发现的化合物的抗-药效 结核病体外活动将显着推进结核病药物计划。在目标 6 中，我们将建立一个临床前 用于新结核病候选药物功效测试的小鼠模型。随着这六个目标中每一个目标的完成，AMRS Core 的技术人员随后将资助 RBL 研究人员研究这些动物模型的性能 支持的研究。实现这些目标所获得的人员、仪器和经验也将 用于根据需要开发和支持其他动物模型，以应对新的生物威胁、流行病 或新出现的传染病。