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中文摘要
翻译
虽然在过去的四年中,遗传小鼠模型一直是翻译生物医学研究的支柱 几十年来,由于物种特定的细胞生物学上的差异,小鼠往往无法建立人类疾病的模型 受影响的器官,以及它们基因组的进化差异。事实证明,雪貂是一种极好的 用于模拟传染病(包括SARS-CoV2)和人类大脑、胰腺、 和肺,当小鼠失败的时候。爱荷华大学(UI)是世界上唯一一所能够在基因上 工程雪貂具有多个精确的基因改变,以前只能在小鼠身上实现。这项技术 使得能够构建能够绘制干细胞隔间的命运图的遗传雪貂模型(即, 血统追踪),对人类疾病进行建模,包括那些具有人性化遗传位点的疾病,以及条件遗传学 使用Cre重组酶。由联邦政府资助的国家雪貂研究和资源中心成立了8个 几年前,该公司为创建新的遗传雪貂模型提供服务,在 雪貂,以及现有遗传系的组织和细胞的分布。这一国家资源提供了 为129多名学术研究人员提供服务,其中108人在大学学院之外,目前有8份合同 随着生物技术公司寻求利用雪貂开发遗传和获得性疾病的疗法 模特们。这些服务已经超出了在雪貂身上进行研究和 在爱荷华州立大学校园里安置雪貂。这项提案旨在设计和建造一座研究设施, 位于爱荷华州立大学校园的国家雪貂研究与资源研究所(NFRRI)。拟议中的设施已被 旨在最大限度地发挥协同作用,最大限度地减少与UI现有设施的重叠,并将毗邻和 连接到现有的雪貂扩展外壳(称为BSRF设施)。NFRRI将包含州- 最先进的设备,用于对雪貂受精卵进行基因工程,并在雪貂身上进行研究。程序上的 空间将包括符合美国农业部的无菌手术套件和用于模型创建的单独显微注射室。 除了湿实验室研究空间,专门的程序套房将适应雾化,肺 功能测试和专门的成像设备。NFRRI将主要为学术研究提供服务 研究人员在UI和营利性生物技术公司之外,但也将提供雪貂模型用于研究 这将发生在现有研究设施的主UI园区。此外,选择的位置为 设施拥有毗邻的土地,可用于未来扩展研究空间和雪貂住房,具有长期战略意义 该计划招募NFRRI的下一代领导人,并利用现有的与营利性组织的关系 寻求在临床前雪貂模型中开发人类疾病疗法的生物技术公司。这个 NFRRI的短期和长期战略目标将通过与 爱荷华大学(NFRRI大楼的成本分担)、囊性纤维化基金会和马歇尔农场(The 最大的研究用雪貂饲养者)。
英文摘要
While genetic mouse models have been the backbone of translational biomedical research for the past four decades, mice often fail to model human disease due to species-specific differences in the cell biology of the affected organs, as well as the evolutionary divergence of their genome. The ferret has proven an excellent species for modeling infectious disease (including SARS-CoV2) and human diseases of the brain, pancreas, and lung when mice have failed. The University of Iowa (UI) is the only location in the world capable of genetically engineering ferrets with multiple precise genetic alterations previously only achievable in mice. This technology has enabled the construction of genetic ferret models capable of fate mapping stem cell compartments (i.e., lineage tracing), modeling human diseases including those with humanized genetic loci, and conditional genetics using Cre recombinase. A federally-funded National Ferret Research and Resource Center was formed eight years ago, which provides services for the creation of new genetic ferret models, performing research studies in ferrets, and the distribution of tissues and cells from existing genetic lines. This national resource has provided services to more than 129 academic investigators,108 of which are outside the UI, and currently has 8 contracts with biotechnology companies seeking to develop therapies for genetic and acquired diseases using ferret models. These services have exceeded the capacity of facilities for both performing research in ferrets and housing ferrets on the UI campus. This proposal seeks to design and construct a research facility that will house the National Ferret Research and Resource Institute (NFRRI) on the UI campus. The proposed facility has been designed to maximize synergy and minimize overlap with existing facilities at UI and will be adjacent and connected to existing ferret expansion housing (referred to as the BSRF facility). The NFRRI will contain state- of-the-art equipment for genetically engineering ferret zygotes and performing research in ferrets. Procedural space will include a USDA-compliant sterile surgical suite and separate microinjection room for model creation. In addition to wet lab research space, specialized procedural suites will accommodate nebulization, pulmonary function testing, and specialized imaging equipment. The NFRRI will primarily provide services to academic investigators outside UI and for-profit biotechnology companies, but will also provide ferret models for research that will occur on the main UI campus in existing research facilities. Furthermore, the chosen location for the facility has adjacent land for future expansion of research space and ferret housing with a long-term strategic plan that recruits next-generation leaders of the NFRRI and capitalizes on existing relationships with for-profit biotechnology companies seeking to develop therapies for human diseases in preclinical ferret models. The short- and long-term strategic goals of the NFRRI will be facilitated through financial partnerships with the University of Iowa (cost sharing of the NFRRI building), Cystic Fibrosis Foundation, and Marshall Farms (the largest breeder of ferrets for research).
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Biology of Submucosal Gland Stem Cells in the Airway
  • 批准号:
    10516449
  • 项目类别:
  • 资助金额:
    $74.51万
  • 财政年份:
    2022
  • 负责人:
    JOHN F ENGELHARDT
  • 依托单位:
Biology of Submucosal Gland Stem Cells in the Airway
  • 批准号:
    10649543
  • 项目类别:
  • 资助金额:
    $70.18万
  • 财政年份:
    2022
  • 负责人:
    JOHN F ENGELHARDT
  • 依托单位:
Early Pathogenesis of Cystic Fibrosis Related Diabetes
  • 批准号:
    10599931
  • 项目类别:
  • 资助金额:
    $147.99万
  • 财政年份:
    2021
  • 负责人:
    JOHN F ENGELHARDT
  • 依托单位:
Early Pathogenesis of Cystic Fibrosis Related Diabetes
  • 批准号:
    10397094
  • 项目类别:
  • 资助金额:
    $147.99万
  • 财政年份:
    2021
  • 负责人:
    JOHN F ENGELHARDT
  • 依托单位:
海外基金