U.S.-Switzerland Cooperative Research: Translational Regu- lation of B-glucuronidase

美国-瑞士合作研究：B-葡萄糖醛酸酶的转化调控

• 批准号: 8713385
• 负责人: Kenneth Paigen
• 金额: $ 0.69万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1990-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8713385&HistoricalAwards=false
• 关键词: U.S.; Switzerland; Cooperative; Research; Translational

This award will enable Dr. Kenneth Paigen and one of his colleagues, both from the University of California, Berkeley, to collaborate with Drs. Kurt Pfister and Richard Gitzelmann, University Children's Hospital, Zurich, Switzerland. They will study the genetic regulatory system of the B-glucuronidase gene in mice. Three classes of regulatory mutations involving the gene have been described: (1) systemic mutations that change enzyme levels in all cells, (2) temporal mutations that change the appearance of the enzyme during development of certain tissues, and (3) hormone- response mutations that change the ability of the B-glucuronidase gene to be activated by androgens. The proposed research will be concerned with the effects of the mutations in cell culture systems. The research is expected to lead to further knowledge of the regulation of B-glucuronidase gene expression and of the mechanisms of gene expression in general. It may also ultimately contribute to a better understanding of a particular genetic disorder associated with the lack of this gene's expression. Of more general interest are the expected benefits to be derived from the definition and better understanding of the regulatory steps and mechanisms from mRNA translation to final protein localization and action. The research will benefit from the international collaboration because Dr. Paigen's laboratory is expert in dealing with the genetics and molecular biology of the B-glucuronidase system, and the Swiss laboratory is experienced in applying techniques of cell culture and protein biochemistry to questions of B-glucuronidase regulation. The two laboratories have a successful history of collaboration, and this award will support the international travel necessary for the U.S. group to continue its part of the joint effort.

该奖项将使来自加州大学伯克利分校的Kenneth Paigen博士和他的一位同事能够与瑞士苏黎世大学儿童医院的Kurt Pfister博士和Richard Gitzelmann博士合作。他们将研究小鼠体内B-葡萄糖苷酸酶基因的遗传调控系统。涉及该基因的三类调控突变已被描述：(1)改变所有细胞中酶水平的系统性突变，(2)改变某些组织发育过程中酶的外观的时间突变，以及(3)改变B-葡萄糖苷酸酶基因被雄激素激活的能力的激素反应突变。拟议的研究将关注细胞培养系统中突变的影响。这项研究有望进一步了解B-葡萄糖苷酸酶基因表达的调控以及基因表达的一般机制。它最终也可能有助于更好地理解与该基因表达缺失相关的特定遗传疾病。更普遍的兴趣是从定义和更好地理解从mRNA翻译到最终蛋白质定位和作用的调控步骤和机制所带来的预期好处。这项研究将受益于国际合作，因为佩根博士的实验室在处理B-葡萄糖苷酸酶系统的遗传学和分子生物学方面是专家，而瑞士实验室在将细胞培养和蛋白质生物化学技术应用于B-葡萄糖苷酸酶调控问题方面经验丰富。这两个实验室有着成功的合作历史，该奖项将支持美国团队继续其共同努力所需的国际旅行。