SIGNALING & METABOLIC ROLES OF GLUCOSE IN SPERM

描述(改编自申请人的摘要)：本建议书描述 葡萄糖在房室划分中作用的比较研究 精子中的代谢和信号通路。据推测， 途径的区域化组织允许新陈代谢的产生 底物和信号效应器在它们所在的精确位置 是必需的，对基本上缺乏底物转运的细胞来说至关重要 能力。提出了三个目标：1)明确 精子功能中糖代谢的区区化；2)表征 精子获能和受精时的葡萄糖摄取 能力；3)剖析连接葡萄糖摄取的信号通路(S)， 新陈代谢和获能。初步数据表明，葡萄糖具有 在获能调控中发挥独特的信号作用。此外, 获能状态显示可以调节葡萄糖的摄取和戊糖 磷酸盐途径。因此，葡萄糖具有一种新的信号机制，影响 获能控制，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。 立即提高了处理不同物种精子的能力 并保持它们的受精能力。尤其是， 繁殖雄性生殖缺陷动物品系的能力 将得到增强。作为动物，这种能力正变得越来越重要 转基因在各种模型中被用于研究目的和用于 药品的生产。拟议工作的临床应用 包括不孕不育的治疗和避孕药具的开发， 对人类医学和物种保护都很重要。 首席调查员(PI)有资格进行以下方面的研究 他既是这一领域的研究科学家，也是一名兽医 对非传统动物的繁殖有特别的兴趣和培训 物种。获得临床(VMD)和研究(PHD)学位 展示了对生物医学研究的职业兴趣，专注于 可供选择的动物模型系统的比较复制。CRRWH 提供一个集成的学术和临床环境，在这个环境中，PI可以 在生殖研究中借鉴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独立生物医学的职业生涯 比较生殖研究人员。

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.