Ribonuclease 7: Antimicrobial Activity in the Human Kidney and Urinary Tract

核糖核酸酶 7：人类肾脏和尿路的抗菌活性

基本信息

批准号：
8280867
负责人：
John David Spencer
金额：
$ 12.91万
依托单位：
RESEARCH INST NATIONWIDE CHILDREN'S HOSP
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8280867
关键词：
Affect Amino Acid Sequence Amino Acids Antibiotic Resistance Antibiotics Atomic Force Microscopy Bacteria Bacterial Infections Biological Biological Assay Biological Markers Biological Process Caring Charge Childhood Clinical Clinical Research Collaborations Communication DNA Defense Mechanisms Diagnosis Diagnostic Disease Down-Regulation Education Environment Faculty Frequencies Goals Health Healthcare Human Hydrophobicity Immune response Immune system Infection K-Series Research Career Programs Kidney Laboratories Leadership Learning Membrane Mentors Mentorship Molecular Mutagenesis Nephrology Ohio Oral Outcome Patients Peptide Sequence Determination Physicians Play Prevention Production Property Proteins Recombinants Regulation Research Research Design Research Project Grants Research Proposals Ribonucleases Role Scientist Services Single Nucleotide Polymorphism Site Sterility Structure Testing Therapeutic Training Universities Up-Regulation Urinary tract Urinary tract infection Urine Work Writing antimicrobial antimicrobial peptide bacterial resistance base career design experience improved interest microbial mutant novel novel diagnostics skills success traditional therapy translational study treatment strategy urinary

项目摘要

DESCRIPTION (provided by applicant): The candidate's long-term goal is to become an accomplished independent physician-scientist in academic pediatric nephrology with clinical and research expertise in the diagnosis, treatment, and prevention of urinary tract infections (UTI). This mentored K08 Career Development Award proposal outlines a plan where the candidate will train under the guidance of a team of mentors and collaborators that have a successful track record of working together. This Research Advisory Team has extensive experience and success in guiding trainees and junior faculty to successful careers as independent physician-scientists. The candidate will benefit from state-of-the-art facilities and extensive support from clinical, basic, and general core services. He will acquire new research and analytical skills from hands-on directed laboratory mentorship and a classroom- based education at The Ohio State University. He will build a repertoire of competencies in oral and written scientific communication; academic team leadership and collaboration; and grantsmanship. The long-term objectives of the proposed research project are to improve the care of pediatric patients with UTIs by identifying effective early biomarkers and novel treatment options for the diagnosis and treatment of UTIs. The proposed research project will test the hypothesis that antimicrobial peptides (AMP), a ubiquitous component of the innate immune system, are important in the regulation and prevention of UTIs. The proposed research will define the function of a novel AMP, ribonuclease 7 (RNase 7), which has recently been shown to have potent antimicrobial properties and play an important role in maintaining urinary tract sterility. The anticipated outcome of this work is advancement of our understanding of the role of RNase 7 in the prevention and treatment of UTIs and to identify the potential use of this protein in UTI diagnostics and therapeutics. Specific Aim 1 is designed to characterize the antimicrobial properties of RNase 7 in states of health and infection. Specific Aim 2 is designed to characterize RNase 7 at the structural and functional level by identifying critical amino acid residues that are responsible for its antimicrobial function. Specific Aim 3 is designed to evaluate the frequency and biological relevance of single nucleotide polymorphisms in RNASE7. Successful completion of these proposed aims and educational plan will help develop the needed expertise to systematically evaluate AMPs, like RNase 7, in the human urinary tract. PUBLIC HEALTH RELEVANCE: Urinary tract infections are one of the most common and serious bacterial infections encountered by physicians. No treatment strategy has proven to be effective in the prevention of UTI sequelae, and antibiotic resistance is increasing in uropathogenic bacteria. Antimicrobial peptides (AMP), a component of the innate immune system, are a promising new class of potential antibiotics that may overcome the limitations of traditional therapies and the emerging problems of bacterial resistance. In this study, we will evaluate the structure, function, and biological relevance of ribonuclease 7, a novel AMP that has potent antimicrobial properties in the human urinary tract.

描述（由申请人提供）：候选人的长期目标是成为学术儿科肾病学领域一位卓有成就的独立医师科学家，在尿路感染（UTI）的诊断、治疗和预防方面拥有临床和研究专业知识。这份指导型 K08 职业发展奖提案概述了一项计划，候选人将在拥有成功合作记录的导师和合作者团队的指导下进行培训。该研究咨询团队在指导实习生和初级教师作为独立的医师科学家取得成功的职业生涯方面拥有丰富的经验和成功。候选人将受益于最先进的设施以及临床、基础和一般核心服务的广泛支持。他将从中获得新的研究和分析技能俄亥俄州立大学的实践指导实验室指导和课堂教育。他将建立口头和书面科学交流的能力；学术团队的领导和协作；和赠款。拟议研究项目的长期目标是通过确定有效的早期生物标志物和诊断和治疗尿路感染的新治疗方案来改善尿路感染儿科患者的护理。拟议的研究项目将检验这样的假设：抗菌肽（AMP）是先天免疫系统中普遍存在的组成部分，在调节和预防尿路感染方面发挥着重要作用。拟议的研究将定义一种新型 AMP、核糖核酸酶 7 (RNase 7) 的功能，该酶最近被证明具有有效的抗菌特性，并在维持尿道无菌方面发挥着重要作用。这项工作的预期成果是加深我们对 RNase 7 在预防和治疗 UTI 中的作用的理解，并确定该蛋白质在 UTI 诊断和治疗中的潜在用途。具体目标 1 旨在表征 RNase 7 在健康和感染状态下的抗菌特性。具体目标 2 旨在通过鉴定负责其抗菌功能的关键氨基酸残基，在结构和功能水平上表征 RNase 7。具体目标 3 旨在评估 RNASE7 中单核苷酸多态性的频率和生物学相关性。成功完成这些拟议目标和教育计划将有助于开发系统评估人类泌尿道中的 AMP（如 RNase 7）所需的专业知识。公共卫生相关性：尿路感染是医生遇到的最常见和最严重的细菌感染之一。目前还没有任何治疗策略被证明可以有效预防尿路感染后遗症，并且泌尿道致病细菌的抗生素耐药性正在增加。抗菌肽（AMP）是先天免疫系统的一个组成部分，是一类很有前途的新型潜在抗生素，可以克服传统疗法的局限性和新出现的细菌耐药性问题。在这项研究中，我们将评估核糖核酸酶 7 的结构、功能和生物学相关性，核糖核酸酶 7 是一种新型 AMP，在人类泌尿道中具有有效的抗菌特性。