SIGNALING & METABOLIC ROLES OF GLUCOSE IN SPERM

信令

• 批准号: 6189985
• 负责人: ALEXANDER J TRAVIS
• 金额: $ 10.75万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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/6189985
• 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（改编自申请人摘要）：本提案描述了 葡萄糖在室间隔化中作用的比较研究 精子中的代谢和信号通路。 它是假设 区域化组织的途径，使生产的代谢 底物和信号效应物在它们所处的精确点上， 需要，对基本上缺乏基质转运的细胞至关重要 能力的 提出了三个目标：1）确定 精子功能中的区室化葡萄糖代谢; 2）表征 精子获能和受精时的葡萄糖摄取 感受态;和3）剖析连接葡萄糖摄取的信号通路， 新陈代谢和获能。 初步数据表明，葡萄糖具有 在获能控制中的独特信号作用。 此外，本发明还提供了一种方法， 获能状态显示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， 控制获能，获能状态调节 葡萄糖代谢 这些研究的研究和工业应用将受到赞赏 立即提高了处理不同物种精子的能力 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 将得到加强。 这种能力在动物身上变得越来越重要 各种模型中的转基因被用于研究目的， 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， 对人类医学和物种保护都很重要。 主要研究者（PI）有资格进行这些研究， 他既是一名研究科学家，在这一领域发表了论文， 在非传统生殖领域有特殊兴趣和训练的妇女， 物种 获得临床（VMD）和研究（博士）学位 表现出对生物医学研究的职业兴趣，专注于 替代动物模型系统的比较再现。 关于CRRWH 提供了一个综合的学术和临床环境，PI可以 借鉴生殖研究领域公认的领导者的专业知识。 通过允许PI接受分子生物学，生物化学， 和配子处理，SERCA将作为PI之间的桥梁， 目前的博士后培训和职业生涯作为一个独立的生物医学 比较生殖学研究者。