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

该奖项将使来自加州大学伯克利分校的肯尼斯·佩根博士及其一位同事能够与奥巴马博士合作。Kurt Pfister和Richard Gitzelmann，瑞士苏黎世大学儿童医院。他们将研究小鼠b -葡萄糖醛酸酶基因的遗传调控系统。已经描述了涉及该基因的三类调节突变：(1)改变所有细胞中酶水平的系统性突变，(2)在某些组织发育过程中改变酶外观的时间性突变，以及(3)激素反应突变，改变b -葡萄糖醛酸酶基因被雄激素激活的能力。拟议的研究将涉及细胞培养系统中突变的影响。该研究有望进一步了解b -葡糖醛酸酶基因表达的调控以及基因表达的一般机制。它也可能最终有助于更好地理解与缺乏该基因表达相关的特定遗传疾病。更普遍的兴趣是，从mRNA翻译到最终蛋白质定位和作用的调控步骤和机制的定义和更好的理解所带来的预期益处。该研究将受益于国际合作，因为Paigen博士的实验室在处理b -葡糖醛酸酶系统的遗传学和分子生物学方面是专家，而瑞士实验室在应用细胞培养和蛋白质生物化学技术解决b -葡糖醛酸酶调节问题方面经验丰富。这两个实验室有着成功的合作历史，该奖项将支持美国小组继续其共同努力所必需的国际旅行。

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.