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：
8662257
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/8662257
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.

描述（由申请人提供）：候选人的长期目标是成为学术儿科肾脏学领域的独立医师科学家，并具有诊断，治疗和预防尿路感染（UTI）方面的临床和研究专业知识。这项指导的K08职业发展奖提案概述了一项计划，其中候选人将在一群导师和合作者的指导下进行培训，这些团队与合作成功的记录有了成功的记录。该研究咨询团队在指导学员和初级教师的职业生涯中具有丰富的经验和成功，成为独立的医师科学家。候选人将从最先进的设施中受益，并从临床，基本和一般核心服务中获得广泛的支持。他将从俄亥俄州立大学的实践实验室指导和基于教室的教育。他将建立口头和书面科学交流能力的曲目；学术团队的领导与协作；和授予技巧。拟议的研究项目的长期目标是通过识别有效的早期生物标志物和新型治疗选择来改善尿路运动的儿科患者的护理，以诊断和治疗UTI。拟议的研究项目将检验以下假设：抗菌肽（AMP）是先天免疫系统的无处不在组成部分，对UTI的调节和预防至关重要。拟议的研究将定义一种新型放大器核糖核酸酶7（RNase 7）的功能，该功能最近已被证明具有有效的抗菌特性，并在维持尿路不育方面起着重要作用。这项工作的预期结果是我们对RNase 7在预防和治疗UTI的作用的理解的发展，并确定该蛋白在UTI诊断和治疗剂中的潜在使用。特定目标1旨在表征卫生和感染状态中RNase 7的抗菌特性。特定的目标2旨在通过识别负责其抗菌功能的关键氨基酸残基来表征在结构和功能水平上的RNase 7。特定目标3旨在评估RNase7中单核苷酸多态性的频率和生物学相关性。这些拟议的目标和教育计划的成功完成将有助于发展人类尿路中系统评估RNase 7之类的AMP所需的专业知识。