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

描述(申请人提供)美国盆腔器官脱垂的管理和治疗目前每年的费用超过10亿美元。弹性蛋白，即 弹性纤维的主要蛋白质成分，赋予脊椎动物组织如心脏、肺和皮肤以显著的弹性。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，被认为在阴道和盆腔器官脱垂的病理生理学中起着关键作用。 这一建议的中心假设是，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。这项建议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中赖氨酸、脯氨酸、缬氨酸、甘氨酸和丙氨酸富含的部分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，只有水化的弹性蛋白才能保持其弹性。该建议的第二个目的是测量不同分娩方式下阴道弹性蛋白中水的动态变化。该项目将利用核磁共振方法进行这些测量。这项提议是跨学科的，涵盖了生物、化学和物理。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，该项目将使用由PI开发的非商业脉冲梯度场来研究水在弹性蛋白中的随时间变化的扩散。该提案的PI是一名物理学助理教授，在核磁共振方法方面拥有丰富的专业知识，并在弹性蛋白方面具有研究经验。PI之前根据NIH SC1提案获得了为期四年的资金。这项提案是一项续展申请，要求再提供四年的资金。这笔持续的资金将通过遵循生物素描中提供的循序渐进的发展计划，帮助PI过渡到非得分支持。

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.