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.

摘要 骨免疫学领域成立于2005年，目的是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，需要几个关键的研究工具和经过严格验证的协议来翻译 在骨髓炎的临床诊断和干预方面的发现在 这个P50研究中心5年前翻译了骨感染的骨免疫学(CoRTOBI)。 因此，我们组建了一支在骨骼病理学方面拥有丰富经验的多学科研究团队， 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、 传染病和矫形外科手术，使该领域的几项突破成为 本次续展申请的科学前提。尽管取得了这些重大进展，但更多的检测和技术 需要发展才能完成CoRTOBI的长期目标。因此，世界银行的更新目标 骨免疫学研究的核心是：1)为CoRTOBI研究人员提供最先进的骨骼 其他地方没有的感染研究资源；以及2)开发新的技术和分析方法，以 骨感染的未来骨免疫学研究。我们实现这些目标的方法体现在 以下是具体目标。在目标1中，我们将处理样品并进行所有的电子显微镜检查 (EM)在感染的骨骼上和制造的纳米孔膜上，在项目1中， 项目2，以及外部合作，使用在上一次供资期间公布的EM方法。在AIM 2.1中 我们将制造新型抗生素药物筛选所需的所有µSIM-CA设备。在AIM 2.2中，我们将 开发和验证新型的µSIM-OLCN设备来评估金黄色葡萄球菌的趋触性和趋杜性 探讨金黄色葡萄球菌侵袭和定植皮质骨OLCN的机制 慢性骨髓炎，在AIM 2.3中，Core将在µSIM-CA和µSIM-OLCN上开发表面涂层 芯片能够对金黄色葡萄球菌在不对称二元分裂期间的粘附性和刚性进行假设测试。在AIM 3.1我们将执行所有Luminex多重分析以进行免疫蛋白质组和细胞因子分析，并在AIM 3.2我们将把这项用于研究的实验分析转化为当天的、高通量的临床诊断 基于阵列成像反射仪技术的StaffAIR，允许自动 抗S抗体检测。近乎实时的金黄色抗体。骨免疫学核心也将促进 试点和可行性项目方案中的新兴技术和研究(即活体显微镜以 量化金黄色葡萄球菌在植入物中定植期间的“表面竞赛”；自动化胶带收集 超微切割机(ATUMtome)/扫描电子显微镜方法，用于对感染的OLCN进行3D成像；以及StaffAIR的扩展)。 重要的是，我们也打算与CoRTOBI以外的调查人员共享我们的资源，以及 将我们的研究平台转移到其他机构，专注于骨感染的研究。