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

描述（由申请人提供）：候选人的长期目标是成为一名在学术儿科肾脏病学方面有成就的独立医生-科学家，在诊断，治疗和预防尿路感染（UTI）方面具有临床和研究专业知识。这个辅导K 08职业发展奖提案概述了一个计划，候选人将在一个导师和合作者团队的指导下进行培训，这些导师和合作者具有成功的合作记录。该研究咨询团队在指导学员和初级教师作为独立的医生科学家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和临床，基础和一般核心服务的广泛支持。他将获得新的研究和分析技能， 在俄亥俄州州立大学的指导实验室指导和课堂教学。他将建立在口头和书面科学交流能力的剧目;学术团队的领导和协作;和granische。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用于诊断和治疗UTI的新型治疗方案来改善UTI儿科患者的护理。拟议的研究项目将测试假设抗菌肽（AMP），先天免疫系统的普遍存在的组成部分，是重要的调节和预防尿路感染。拟议的研究将定义一种新型AMP，核糖核酸酶7（RNase 7）的功能，最近已被证明具有有效的抗菌特性，并在维持尿路无菌中发挥重要作用。这项工作的预期成果是我们对RNase 7在预防和治疗UTI中的作用的理解，并确定这种蛋白质在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RNASE 7中单核苷酸多态性的频率和生物学相关性。成功完成这些拟议的目标和教育计划将有助于发展所需的专业知识，以系统地评估人类尿路中的AMP，如RNase 7。

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.