Regulation of Slo Splicing in the Urogenital Systme

描述(由申请人提供)： 凯文·戴维斯博士有多年的分子生物学家经验。他最近进入了一个新的研究领域，泌尿学。这份K01申请将使他在泌尿生殖生理学的基本概念方面获得经验。然后，他将处于一个理想的位置，将分子生物学技术应用于泌尿外科领域的基本问题，成为一名独立的研究员。 该部门。阿尔伯特·爱因斯坦医学院的泌尿外科是获得泌尿生殖生理学经验的绝佳环境。它拥有一个活跃的多学科研究小组，其中包括泌尿外科领域的领军人物，如阿诺德·梅尔曼博士和乔治·基督博士。该部门进行临床和基础研究，并积极将这项工作从实验室转化为临床疗法。 为了获得泌尿生殖生理学方面的经验，本研究项目将在体内和体外研究激素对泌尿生殖道平滑肌组织中Slo基因剪接的影响。我们的工作假设是，SIO亚型在平滑肌细胞中的表达受激素的调节，而且，这些亚型表达的变化与泌尿生殖系统的生理/功能障碍有关。具体地说，我们将观察荷尔蒙(应激轴荷尔蒙和性激素)对雌性大鼠体内Slo基因剪接的影响。将在这些动物(主动脉、结肠、膀胱和阴道)的平滑肌组织中监测Slo基因剪接的变化。不同剪接形式的Slo基因将以其细胞和生理功能为特征。此外，还将开发一种报告结构，可以实时分析培养的大鼠平滑肌细胞(主动脉、结肠、膀胱和阴道)的剪接情况。将分析激素在这个体外系统中影响剪接的能力，以及对决定Slo剪接的信号通路的研究。 这一研究项目将使戴维斯博士对泌尿生殖生理学有一个透彻的了解，同时使他能够利用他在分子生物学方面的经验。

DESCRIPTION (provided by applicant): Dr. Kevin Davies has several years of experience as a molecular biologist. He has recently entered a new field of study, Urology. This K01 application will allow him to gain experience in the basic concepts of urogenital physiology. He will then be in an ideal position to apply the techniques of molecular biology to fundamental problems in the filed of Urology as an independent researcher. The Dept. of Urology at Albert Einstein College of Medicine is an excellent environment to gain experience in urogenital physiology. It has an active multi-disciplinary research group, which includes leaders in the filed of Urology, such as Dr, Arnold Melman and Dr. George Christ. The Dept conducts both clinical and basic research, and is active in translating this work from the laboratory to clinical therapies. In order to gain experience in urogenital physiology this research project will investigate the effect of hormones on splicing of the Slo gene in urogenital smooth muscle tissue in vivo and in vitro. Our working hypothesis is that SIo isoform expression in smooth muscle myocytes is modulated by hormones, and moreover, that these changes in isoform expression are relevant to urogenital physiology/dysfunction. Specifically we will look at the effects of hormones (stress axis hormones and sex hormones on the splicing of the Slo gene in female rats in vivo. Changes in the splicing of the Slo gene will be monitored in the smooth muscle tissue of these animals (aorta, colon, bladder and vagina). The different splice forms of the Slo gene will be characterized for their cellular and physiological function. In addition, a reporter construct will be developed which will allow real time analysis of splicing in cultured rat smooth muscle cells (aorta, colon, bladder and vagina). The ability of hormones to effect splicing in this in vitro system will be analyzed, as well as investigations into the signaling pathways that determine Slo splicing. This research project will allow Dr. Davies to develop a thorough understanding of urogenital physiology, while at the same time allowing him to utilize his experience in molecular biology.