NMR studies of the effects of mode of birth on vaginal elastin

描述（由申请人提供） 目前，美国每年盆腔器官脱垂的管理和治疗费用超过 10 亿美元。弹性蛋白， 弹性纤维的主要蛋白质成分，赋予心脏、肺和皮肤等脊椎动物组织显着的弹性。弹性蛋白结构和功能的丧失是许多人类退行性和遗传性疾病的病理特征，并且被认为在阴道和盆腔器官脱垂的病理生理学中发挥着关键作用。 该提案的中心假设是，与剖腹产相比，阴道分娩会降低阴道弹性蛋白的结构和动力学特性。该提案的目的是通过追求两个独立的目标来定量研究分娩方式对阴道弹性蛋白结构的影响。该提案的第一个目的是测量不同分娩方式下阴道弹性蛋白富含赖氨酸、脯氨酸、缬氨酸、甘氨酸和丙氨酸片段的结构和动力学特性。这种蛋白质区别于其他弹性体的一个关键特征是，它的功能取决于水合作用，只有水合的弹性蛋白才能保持其弹性。该提案的第二个目标是测量各种分娩方式后阴道弹性蛋白中水的动态。该项目将利用核磁共振方法进行这些测量。该提案是跨学科的，涵盖生物学、化学和物理学。该方法包括依赖魔角旋转技术的传统碳13核磁共振技术。此外，该项目将涉及使用由 PI 开发的非商业脉冲梯度场来研究弹性蛋白中水的时间依赖性扩散。该提案的 PI 是一位物理学助理教授，在核磁共振方法方面拥有丰富的专业知识和弹性蛋白的研究经验。该 PI 此前曾根据 NIH SC1 提案获得为期四年的资助。该提案是一项续签申请，要求额外提供四年的资金。这笔持续的资金将帮助 PI 通过遵循简历中提供的逐步发展计划过​​渡到非 SCORE 支持。

DESCRIPTION (provided by applicant) The management and treatment of pelvic organ prolapse in the United States currently exceeds one billion dollars in costs annually. Elastin, the principle protein component of the elastic fiber, imparts vertebrate tissues such as the heart, lungs and skin with remarkable elasticity. The loss of elastin architecture and function is a pathological characteristic of a number of human degenerative and genetic disorders, and is believed to play a critical role in the vagina and in the pathophysiology of pelvic organ prolapse. The central hypothesis of this proposal is that vaginal birth degrades structural and dynamical properties of vaginal elastin compared to cesarean delivery. The objectives of this proposal are to quantitatively investigate the effects of modes of delivery on the structure of elastin of the vagina by pursuing two independent aims. The first aim of the proposal is to measure the structural and dynamical properties of lysine, proline, valine, glycine and alanine rich segments of elastin of the vagina following various modes of delivery. A key characteristic of this protein that distinguishes it from other elastomers is that its function hinges on hydration only hydrated elastin retains its elasticity. The second aim of the proposal is to measure the dynamics of water in vaginal elastin following various modes of delivery. This project will make use of nuclear magnetic resonance methods for these measurements. The proposal is interdisciplinary and encompasses biology, chemistry and physics. The methodology includes conventional carbon-13 nuclear magnetic resonance techniques that rely on magic angle spinning technology. In addition, the project will involve the use of non-commercial pulsed gradient fields, developed by the PI, to study time-dependent diffusion of water in elastin. The PI of the proposal is an Assistant Professor of Physics with significant expertise in nuclear magnetic resonance methodology and research experience in elastin. The PI was previously funded for four years under an NIH SC1 proposal. This proposal is a renewal application requesting four additional years of funding. This continued funding will assist the PI to transition to non-SCORE support by following a stepwise developmental plan provided in the biosketch.