Ocular Surface Microbiome, Virome, and Pathogens in Ophthalmic Disease and Health

眼科疾病与健康中的眼表微生物组、病毒组和病原体

• 批准号: 9533601
• 负责人: Thuy A Doan
• 金额: $ 23.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9533601
• 关键词: Anterior uveitis; Antibiotic Therapy; Antibiotics; Aqueous Humor; Archives; Azithromycin; Bioinformatics; Biological Assay; Biometry; Blindness; California; Clinical; Clinical Microbiology; Clinical Research; Clinical Trials Design; Communicable Diseases; Communities; Complement; Complex; Corneal Ulcer; Data Collection; Detection; Development; Development Plans; Diagnosis; Diagnostic; Diagnostic tests; Disease; Doctor of Medicine; Doctor of Philosophy; Endophthalmitis; Environment; Etiology; Eye Infections; Foundations; Future; Goals; Gold; Health; Herpesviridae; Human; Infectious Agent; Inflammatory; Institution; Institutional Review Boards; Intervention; Investigation; Knowledge; Laboratories; Liquid substance; Mentors; Mentorship; Microbe; Molecular; Molecular Biology; Morbidity - disease rate; Niger; Ophthalmology; Organism; Outcome; Pathogenesis; Patients; Performance; Placebos; Polymerase Chain Reaction; Postoperative Period; Predisposing Factor; Public Health; Randomized Controlled Trials; Reaction; Research; Sampling; San Francisco; Scientist; Sensitivity and Specificity; Shotguns; Specimen; Suggestion; Surface; System; Techniques; Testing; Time; Toxoplasma; Training; Uncertainty; Universities; Uveitis; Viral; Virus; Virus Diseases; Visual; Work; accurate diagnosis; aqueous; bacterial community; base; career; career development; clinical diagnostics; co-infection; conjunctiva; deep sequencing; design; experimental study; improved; innovation; metagenomic sequencing; microbiome; microorganism interaction; molecular diagnostics; multidisciplinary; next generation sequencing; novel; ocular surface; particle; pathogen; prevent; prospective; rRNA Genes; response; skills; success; virome

PROJECT SUMMARY/ABSTRACT This K08 application for Thuy Doan, M.D., Ph.D., describes a five year strategy designed to enhance her research and professional skills with the career goal of becoming an independent clinician scientist advancing the understanding of ocular infectious and inflammatory diseases and improving their treatment. Infectious uveitis and ocular infections are a major cause of ocular morbidity and blindness worldwide. While timely and accurate diagnosis is crucial for improved visual outcomes, a definitive diagnosis is often not possible given the significant knowledge gap in factors predisposing to eye infections and the limitations of available diagnostic tests in ophthalmology. The core hypothesis of this proposal is that the bacterial and viral constituents of the ocular surface are involved in ocular health and disease. The goal of this project is to understand this potential pathogen reservoir, the ocular surface microbiome and virome, and to identify infectious agents involved in ocular infections. We propose to advance the capabilities of ocular molecular diagnostics and enhance the understanding of the pathogenesis of ocular infections with the following aims. The first aim will evaluate the use of a next-generation sequencing (NGS)-based approach as a viable clinical diagnostic test for ocular infections. These experiments will directly compare NGS to the current conventional molecular diagnostics using archived intraocular samples. Prospectively collected aqueous samples will then be assessed for potential pathogens. The second aim will characterize the effects of antibiotics on the bacterial and viral communities using samples collected in a large randomized controlled trial. These studies have the potential to improve the diagnostic paradigm and guide targeted interventions for ocular infections. I am committed to developing a clinical research-oriented career in the field of ophthalmology at a major academic institution and understand the need to pursue additional formal training and mentorship. Key components of the career development plan include: (1) laboratory investigations of the ocular surface microbiome, virome, and causes of ocular infectious diseases; (2) mentorship from a multidisciplinary group of scientists and clinician scientists with expertise in advanced molecular techniques, biostatistics, and clinical trial designs; (3) formal didactics to expand molecular biology, biostatistics, and clinical microbiology knowledge; (4) data collection for R01 application; and (5) planned transition to independence including professional development. A scientific advisory and mentorship committee has been assembled to assure progression toward independence. The career development plan will be carried out at the University of California, San Francisco, which provides an exceptional environment to conduct this research, including state- of-the-art facilities and a world-class and supportive community of scientists all critical to my future success.

项目概要/摘要 Thuy Doan 医学博士、博士的 K08 申请描述了旨在增强她的五年战略 研究和专业技能，职业目标是成为一名独立的临床科学家 了解眼部感染性和炎症性疾病并改善其治疗。 传染性葡萄膜炎和眼部感染是全世界眼部发病和失明的主要原因。尽管 及时、准确的诊断对于改善视力结果至关重要，但明确的诊断通常不是 鉴于对眼部感染诱发因素的巨大知识差距以及现有技术的局限性，这是可能的。 眼科可用的诊断测试。该提案的核心假设是细菌和病毒 眼表的成分与眼部健康和疾病有关。该项目的目标是 了解这种潜在的病原体库、眼表微生物组和病毒组，并识别 与眼部感染有关的感染因子。我们建议提高眼部分子的能力 诊断并增强对眼部感染发病机制的了解，目的如下。 第一个目标是评估基于下一代测序（NGS）的方法作为可行的临床方法的使用情况 眼部感染的诊断测试。这些实验将直接将NGS与当前的传统方法进行比较 使用存档的眼内样本进行分子诊断。然后前瞻性收集的水样 评估潜在的病原体。第二个目标将描述抗生素对细菌的影响 和病毒群落，使用在大型随机对照试验中收集的样本。这些研究有 改善诊断范式并指导眼部感染的针对性干预措施的潜力。 我致力于在眼科领域发展以临床研究为导向的职业生涯 学术机构并了解寻求额外正式培训和指导的必要性。钥匙 职业发展计划的组成部分包括： (1) 眼表实验室检查 微生物组、病毒组和眼部传染病的病因； (2)来自多学科小组的指导 具有先进分子技术、生物统计学和临床​​专业知识的科学家和临床科学家 试验设计； (3) 扩展分子生物学、生物统计学和临床​​微生物学的正式教学 知识; (4) R01申请数据收集； (5) 计划过渡到独立，包括 专业发展。成立了一个科学咨询和指导委员会，以确保 走向独立的进展。职业发展计划将在大学进行 加利福尼亚州、旧金山为开展这项研究提供了优越的环境，包括州- 最先进的设施和世界一流的支持性科学家社区对我未来的成功至关重要。