Nasopharyngeal Microbiome and Risk of Bacterial Pathogen Colonization in Infants

婴儿鼻咽微生物组和细菌病原体定植的风险

• 批准号: 10159201
• 负责人: Matthew Scott Kelly
• 金额: $ 16.23万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-23 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159201
• 关键词: 16S ribosomal RNA sequencing; Accounting; Advisory Committees; Africa; Africa South of the Sahara; Bacteria; Bioinformatics; Botswana; Cessation of life; Child; Childhood; Clinical; Clinical Research; Communicable Diseases; Computational Biology; Country; Coupled; Data; Development; Development Plans; Exposure to; Faculty; Fellowship; Funding; Generations; Goals; Haemophilus influenzae; Host resistance; Immune system; Incidence; Infant; Infection; Infrastructure; International; Knowledge; Lead; Low Birth Weight Infant; Lower respiratory tract structure; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodological Studies; Methods; Microbiology; Modeling; Mothers; Nasopharynx; Nutrient; Pediatric Hospitals; Pediatrics; Philadelphia; Pneumococcal conjugate vaccine; Pneumonia; Prevention; Probiotics; Production; Prospective cohort study; Recording of previous events; Reporting; Research; Research Personnel; Respiratory Tract Infections; Risk; Sampling; Seeds; Smoke; Statistical Methods; Streptococcus pneumoniae; System; Testing; Training; Training Activity; United States National Institutes of Health; Universities; Upper respiratory tract; career; career development; commensal bacteria; design; educational atmosphere; experience; global health; gut microbiome; high risk; host-microbe interactions; infancy; insight; intervention effect; longitudinal analysis; low and middle-income countries; member; microbial genomics; microbiome; microbiome analysis; microbiome research; microbiome sequencing; novel; pathogenic bacteria; prevent; professor; programs; prospective; research and development; research study; respiratory pathogen; respiratory virus; skills; solid fuel; statistics; therapy development

ABSTRACT This Mentored Patient-Oriented Research Career Development Award proposal will provide an excellent educational environment, expert mentorship, and didactic and practical training to facilitate Dr. Matthew Kelly’s development as an independent investigator. Dr. Kelly’s long-term career goal is to develop strategies that use targeted manipulation of the microbiome to prevent and treat infections in children. The proposed research, involving mother-infant pairs in Botswana, will provide insight into the potential impact of the nasopharyngeal microbiome on the risk of childhood pneumonia. Pneumonia is the leading infectious killer of children globally, accounting for 920,000 deaths each year. More than half of these deaths occur in sub-Saharan Africa. Colonization of the nasopharynx precedes pneumonia caused by bacterial pathogens, and the nasopharyngeal microbiome may serve as a barrier to colonization and invasion of the lower respiratory tract by these bacteria. In this proposal, Dr. Kelly will use Streptococcus pneumoniae as a model to further knowledge of the dynamic interactions between the nasopharyngeal microbiome and bacterial respiratory pathogens. He will also develop a systematic approach for the application of conventional multivariable statistics to the analysis of longitudinal microbiome data. The candidate is an Assistant Professor of Pediatrics in the Division of Infectious Diseases at Duke University. He was previously the Africa Fellow in the David N. Pincus Global Health Fellowship through the Children’s Hospital of Philadelphia, and has been conducting clinical research studies in Botswana since 2012. Dr. Kelly’s short-term goals for the K23 program are: 1) acquire bioinformatics and computational biology skills for the analysis of microbiome sequencing data; 2) obtain additional expertise in the design and conduct of prospective clinical studies in children; and 3) develop a model for use of conventional multivariable statistical methods in analyses of longitudinal microbiome data. Dr. Kelly’s mentorship team has expertise in the microbiome, bioinformatics, conventional multivariable statistics, and global health research, and a history of successful mentorship of junior faculty. Dr. Kelly’s primary mentor, Dr. Rawls, leads an NIH-funded research program studying the microbiome and host-microbe interactions. His co-mentors, Drs. Cunningham and Hudgens, have expertise in the conduct of international clinical research and the development of novel statistical methodologies for studies of infectious diseases, respectively. His external advisor, Dr. Steenhoff, has more than 10 years of clinical research experience in Botswana and will assist with study implementation. The remaining members of Dr. Kelly’s external advisory committee are experts in the early infant microbiome (Seed) and pediatric pneumonia (Shah). The proposed research could ultimately lead to development of the first rationally- designed probiotics for the prevention of pneumonia and other respiratory infections. Upon completion of the career development and research plans, Dr. Kelly will have the necessary skillset to lead clinical studies that use targeted manipulation of the microbiome for the prevention and treatment of infections in children.

抽象的 这项受到指导的以患者为导向的研究职业发展奖提案将提供出色的 教育环境，专家心态以及教学和实践培训，以促进Matthew Kelly博士 作为独立研究者的发展。凯利博士的长期职业目标是制定使用的策略 针对微生物组的有针对性操纵，以预防和治疗儿童感染。拟议的研究， 涉及博茨瓦纳的母亲对，将洞悉鼻咽的潜在影响 微生物组关于儿童期肺炎的风险。肺炎是全球儿童的主要传染性杀手， 每年占920,000人死亡。这些死亡中有一半以上发生在撒哈拉以南非洲。 鼻咽的定植先于由细菌病原体引起的肺炎和鼻咽 微生物组可能是这些细菌对下呼吸道侵袭和侵袭的障碍。 在此提案中，凯利博士将使用肺炎链球菌作为进一步了解动态的模型 鼻咽微生物组和细菌呼吸道病原体之间的相互作用。他也会发展 用于将常规多变量统计数据应用于纵向分析的系统方法 微生物组数据。该候选人是在传染病分区的儿科助理教授 杜克大学。他以前曾是大卫·普林​​斯（David N. Pincus）全球健康奖学金中的非洲研究员 费城儿童医院，此后一直在博茨瓦纳进行临床研究 2012年。凯利博士的K23计划的短期目标是：1）获取生物信息学和计算生物学 分析微生物组测序数据的技能； 2）获得设计和行为的其他专家 儿童的前瞻性临床研究； 3）开发用于使用常规多变量统计的模型 纵向微生物组数据分析中的方法。凯利博士的Mentalship团队在 微生物组，生物信息学，常规多变量统计和全球健康研究，以及 初级教师的成功心态。凯利博士的主要心态罗尔斯博士领导了一项NIH资助的研究 研究微生物组和宿主微叶相互作用的程序。他的联合官员，博士。坎宁安和 哈金斯，在国际临床研究的进行和新统计数据的发展方面具有专业知识 传染病研究的方法。他的外部顾问Steenhoff博士拥有的 博茨瓦纳（Botswana）的10年临床研究经验将有助于研究实施。其余 凯利（Kelly）博士外部咨询委员会的成员是早期婴儿微生物组（种子）和 小儿肺炎（Shah）。拟议的研究最终可能导致第一个合理发展的发展 为预防肺炎和其他呼吸道感染设计了益生菌。完成后 职业发展和研究计划，凯利博士将拥有必要的技能来领导使用的临床研究 针对微生物组的有针对性操纵儿童感染的预防和治疗。