Osteoimmunology Core

骨免疫学核心

• 批准号: 10402965
• 负责人: Benjamin L Miller
• 金额: $ 44.72万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10402965
• 关键词: 3-Dimensional; Adhesions; Antibiotic Resistance; Antibiotics; Antibodies; Behavior; Biological Assay; Biophysics; Cells; Chronic; Clinical; Collaborations; Communicable Diseases; Development; Devices; Drug Screening; Electron Microscopy; Emerging Technologies; Engineering; Funding; Future; Goals; Hematopoietic; Host Defense; Human; Image; Immune; Immunoassay; Immunology; Immunology procedure; Implant; In Vitro; Infection; Institution; Intervention; Laser Scanning Microscopy; Legal patent; Measurement; Membrane; Methods; Microfluidics; Microtome - medical device; Monoclonal Antibodies; Musculoskeletal; Nanoporous; ORALIT; Occupations; Orthopedic Surgery; Osteocytes; Osteomyelitis; Pathogenesis; Pathology; Patients; Process; Proteome; Protocols documentation; Publications; Publishing; RNA vaccine; Race; Research; Research Personnel; Resources; Risk Factors; Sampling; Serum; Services; Silicon; Staphylococcal Infections; Staphylococcus aureus; Surface; Technology; Testing; Three-Dimensional Imaging; Time; Translating; Translational Research; antibody diagnostic; assay development; base; bone; clinical diagnostics; cortical bone; cost efficient; cytokine; experience; innovation; innovative technologies; intravital microscopy; materials science; microbial; microscopic imaging; multidisciplinary; multiplex assay; new technology; novel; osteoimmunology; prognostic; programs; surface coating; technology development; tool; vaccine trial

Abstract The field of Osteoimmunology was established in 2005 to understand how bone influences immune and hematopoietic cells, as well as how hematopoietic and immune cells influence bone, in clinical conditions like osteomyelitis. However, several critical research tools and rigorously validated protocols required to translate discoveries into clinical diagnostics and interventions for osteomyelitis did not exist at the commencement of this P50 Center of Research Translation on the Osteoimmunology of Bone Infection (CoRTOBI) 5 years ago. Thus, we assembled a multidisciplinary team of investigators with extensive experience in bone pathology, microbial pathogenesis, immunology, electron microscopy, biophysics, material science & engineering, infectious disease and orthopaedic surgery, to enable several breakthroughs in the field that serve as the scientific premise of this renewal application. Despite these major advances, additional assay and technology development is needed to complete the long-term goals of CoRTOBI. Thus, the renewal goals of the Osteoimmunology Research Core are to: 1) provide the CoRTOBI investigators with state-of-the-art bone infection research resources that do not exist elsewhere; and 2) develop novel technologies and assays for future osteoimmunology research on bone infection. Our approaches to achieve these goals are embodied by the following Specific Aims. In Aim 1 we will process the samples and perform all of the electron microscopy (EM) on the infected bone and fabricated nanoporous membranes in Project 1, the mRNA vaccine studies in Project 2, and external collaborations, using EM methods published during the prior funding period. In Aim 2.1 we will fabricate all of the µSiM-CA devices needed for novel antibiotic drug screening. In Aim 2.2 we will develop and validate novel µSiM-OLCN devices to assess haptotaxis and durotaxis behaviors of S. aureus in vitro to elucidate the mechanism of S. aureus invasion and colonization of the OLCN of cortical bone during chronic osteomyelitis, and in Aim 2.3 the Core will develop surface coatings on the µSiM-CA and µSiM-OLCN chips to enable hypothesis testing of S. aureus adhesion and rigidity during asymmetric binary fission. In Aim 3.1 we will perform all of Luminex-multiplex assays for immune proteome and cytokine analyses, and In Aim 3.2 we will translate this experimental assay for research into a same-day, high throughput clinical diagnostic called StaphAIR based on Arrayed Imaging Reflectometry technology that allows for the automated measurement of anti-S. aureus antibodies in near-real time. The Osteoimmunology Core will also facilitate emerging technologies and research in the Pilot and Feasibility Project Program (i.e. intravital microscopy to quantify “the race for the surface” during S. aureus colonization of bone implants; automated tape-collecting ultra-microtome (ATUMtome)/SEM methods for 3D imaging of infected OLCN; and an extension of StaphAIR). Importantly, it is also our intent to share our resources with investigators outside of this CoRTOBI, and transport our research platforms to other institutions with a research focus on bone infections.

抽象的 骨免疫学领域成立于 2005 年，旨在了解骨骼如何影响免疫和 造血细胞，以及造血细胞和免疫细胞如何影响骨骼，在临床条件下，如 骨髓炎。然而，翻译需要一些关键的研究工具和严格验证的协议 骨髓炎的临床诊断和干预措施的发现在科学开始时并不存在 这个P50骨感染骨免疫学研究翻译中心（CoRTOBI）5年前。 因此，我们组建了一个由在骨病理学方面拥有丰富经验的多学科研究人员组成的团队， 微生物发病机制、免疫学、电子显微镜、生物物理学、材料科学与工程、 传染病和骨科手术，在该领域取得多项突破 本次续签申请的科学前提。尽管取得了这些重大进展，但还需要额外的测定和技术 完成CoRTOBI的长期目标需要开发。因此，更新目标 骨免疫学研究核心是：1) 为 CoRTOBI 研究人员提供最先进的骨骼 其他地方不存在的感染研究资源； 2）开发新技术和检测方法 未来骨感染的骨免疫学研究。我们实现这些目标的方法体现在 以下具体目标。在目标 1 中，我们将处理样品并执行所有电子显微镜检查 （EM）在项目 1 中受感染的骨骼和制造的纳米孔膜上，mRNA 疫苗研究 项目 2 和外部合作，使用先前资助期间发布的 EM 方法。瞄准2.1 我们将制造新型抗生素药物筛选所需的所有 µSiM-CA 设备。在目标 2.2 中，我们将 开发并验证新型 µSiM-OLCN 设备，以评估金黄色葡萄球菌的触触性和杜旋性行为 体外阐明金黄色葡萄球菌侵入皮质骨 OLCN 并定植的机制 慢性骨髓炎，在目标 2.3 中，Core 将在 µSiM-CA 和 µSiM-OLCN 上开发表面涂层 芯片，以实现不对称二元裂变期间金黄色葡萄球菌粘附和刚性的假设检验。瞄准 3.1 我们将进行所有用于免疫蛋白质组和细胞因子分析的 Luminex 多重测定，以及 In Aim 3.2 我们将把这种研究实验测定转化为当天的高通量临床诊断 称为 StaphAIR，基于阵列成像反射技术，可实现自动化 抗S的测量。近乎实时的金黄色葡萄球菌抗体。骨免疫学核心还将促进 试点和可行性项目计划中的新兴技术和研究（即活体显微镜 量化金黄色葡萄球菌在骨植入物定植过程中的“表面竞争”；自动磁带收集 用于受感染 OLCN 3D 成像的超薄切片机 (ATUMtome)/SEM 方法；以及 StaphAIR 的扩展）。 重要的是，我们还打算与 CoRTOBI 之外的研究人员共享我们的资源，并且 将我们的研究平台转移到其他专注于骨感染研究的机构。