SIGNALING & METABOLIC ROLES OF GLUCOSE IN SPERM

信令

• 批准号: 6699227
• 负责人: ALEXANDER J TRAVIS
• 金额: $ 9.69万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6699227
• 关键词: cats; fertilization; glucose metabolism; glucose transport; intracellular transport; laboratory mouse; male; sperm

DESCRIPTION (Adapted from the applicant's abstract): This proposal describes a comparative investigation of the roles of glucose in compartmentalized metabolic and signaling pathways in sperm. It is hypothesized that regionalized organization of pathways allows the production of metabolic substrates and signaling effectors at the precise points where they are needed, crucial to cells largely devoid of substrate-translocating capabilities. Three Aims are proposed: 1) to define the roles of compartmentalized glucose metabolism in sperm function; 2) to characterize glucose uptake in sperm as they capacitate and attain fertilization competence; and 3) to dissect the signaling pathway(s) linking glucose uptake, metabolism, and capacitation. Preliminary data suggest that glucose has a unique signaling role in the control of capacitation. In addition, capacitation status is shown to regulate glucose uptake and the pentose phosphate pathway. Thus glucose has a novel signaling mechanism effecting the control of capacitation, and capacitation status regulates key pathways of glucose metabolism. Research and industrial applications of these studies will be appreciated immediately in an increased ability to handle the sperm of different species in vitro and to maintain their fertilization competence. In particular, the ability to propagate lines of animals with male-related defects in fertility will be enhanced. This ability is becoming increasingly important as animal transgenesis in a variety of models is utilized for research purposes and for the production of pharmaceuticals. Clinical applications of the proposed work include treatment of infertility and the development of contraceptives, important both for human medicine and species preservation. The Principal Investigator (PI) is qualified to perform these studies in that he is both a research scientist, published in this field, and a veterinarian with special interest and training in the reproductive of non-traditional species. Attaining both clinical (VMD) and research (PhD) degrees demonstrates a career interest in biomedical research, focusing on the comparative reproduction of alternative animal model systems. The CRRWH offers an integrated academic and clinical environment from which the PI can draw upon the expertise of recognized leaders in the study of reproduction. By allowing the PI to train in techniques of molecular biology, biochemistry, and gamete handling, the SERCA will function as a bridge between the PI's current postdoctoral training and a career as an independent biomedical researcher in comparative reproduction.

描述（改编自申请人的摘要）：该提案描述了 葡萄糖在区室化中作用的比较研究 精子的代谢和信号传导途径。 假设 路径的区域化组织允许代谢的产生 底物和信号效应器位于其所在的精确位置 需要，对于基本上没有底物易位的细胞至关重要 能力。 提出了三个目标：1）定义 精子功能中的区室化葡萄糖代谢； 2）表征 精子在获得能力和受精时摄取葡萄糖 权限; 3) 剖析连接葡萄糖摄取的信号通路， 新陈代谢和能力。 初步数据表明葡萄糖具有 在获能控制中独特的信号传导作用。 此外， 获能状态可调节葡萄糖摄取和戊糖 磷酸途径。 因此，葡萄糖具有一种新的信号传导机制，可影响 获能的控制，获能状态调节关键途径 葡萄糖代谢。 这些研究的研究和工业应用将受到赞赏 立即增强处理不同物种精子的能力 体外并保持其受精能力。 特别是， 繁殖具有雄性相关生育缺陷的动物品系的能力 将得到增强。 作为动物，这种能力变得越来越重要 各种模型中的转基因用于研究目的和 药品的生产。 拟议工作的临床应用 包括治疗不孕症和开发避孕药具， 对于人类医学和物种保护都很重要。 首席研究员 (PI) 有资格进行这些研究： 他既是一名在该领域发表文章的研究科学家，又是一名兽医 对非传统生殖有特殊兴趣并接受过培训 物种。 获得临床（VMD）和研究（PhD）学位 表现出对生物医学研究的职业兴趣，重点关注 替代动物模型系统的比较再现。 CRRWH 提供了一个综合的学术和临床环境，PI 可以从中 借鉴生殖研究领域公认领导者的专业知识。 通过让 PI 接受分子生物学、生物化学技术的培训， 和配子处理，SERCA 将充当 PI 之间的桥梁 目前的博士后培训和独立生物医学的职业生涯 比较再生产研究员。