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分子工具,经典问题——对克利福德·塔宾的访谈。采访者:迈克尔·K·理查森

Molecular tools, classic questions - an interview with Clifford Tabin. Interviewed by Richardson, Michael K.

作者信息

Tabin Clifford

出版信息

Int J Dev Biol. 2009;53(5-6):725-31. doi: 10.1387/ijdb.072575mr.

Abstract

Clifford J. Tabin has made pioneering contributions to several fields in biology, including retroviruses, oncogenes, developmental biology and evolution. His father, a physicist who worked in the Manhattan project, kindled his interest in science. Cliff later chose to study biology and started his research career when the world of recombinant DNA was opening up. In Robert Weinbergs lab, he constructed the Moloney leukaemia virus (MLV-tk), the first recombinant retrovirus that could be used as a eukaryotic vector. He also discovered the amino acid changes leading to the activation of Ras, the first human oncogene discovered. As an independent researcher, he began in the field of urodele limb regeneration, and described the expression of retinoic acid receptor and Hox genes in the blastema. Moving to the chick model, his was one of the labs that simultaneously cloned the first vertebrate hedgehog cognates and showed that sonic hedgehog functions as a morphogen in certain developmental contexts, in particular as an organizing activity during limb development. Comparative studies by Ann Burke in his lab showed that differences in boundaries of Hox gene expression across vertebrate phylogeny correlated with differences in skeletal morphology. The Tabin lab also discovered a genetic pathway responsible for mediating left-right asymmetry in vertebrates; helped uncover the pathways leading to dorsoventral limb patterning; made contributions to our understanding of skeletal morphogenesis and identified developmental mechanisms that might underpin the diversification of the beak in Darwins finches. Despite being a professor of genetics at Harvard, Tabin says: "I have never done a genetics experiment in my life!". This is changing with his latest project: the genetics of Mexican cavefish. I interviewed Cliff on the 3rd October, 2007, in his office at Harvard.

摘要

克利福德·J·塔宾在生物学的多个领域都做出了开创性贡献,包括逆转录病毒、癌基因、发育生物学和进化。他的父亲是一名曾参与曼哈顿计划的物理学家,激发了他对科学的兴趣。克利福德后来选择研究生物学,并在重组DNA领域刚刚兴起时开始了他的研究生涯。在罗伯特·温伯格的实验室里,他构建了莫洛尼白血病病毒(MLV-tk),这是第一个可作为真核载体使用的重组逆转录病毒。他还发现了导致Ras激活的氨基酸变化,Ras是发现的第一个人类癌基因。作为一名独立研究员,他起初从事有尾两栖类肢体再生领域的研究,并描述了视黄酸受体和Hox基因在再生芽基中的表达。转向鸡模型后,他所在的实验室是同时克隆首批脊椎动物刺猬同源基因的实验室之一,并表明音猬因子在某些发育环境中作为一种形态发生素发挥作用,特别是在肢体发育过程中作为一种组织活性物质。他实验室的安·伯克进行的比较研究表明,脊椎动物系统发育中Hox基因表达边界的差异与骨骼形态的差异相关。塔宾实验室还发现了一条负责介导脊椎动物左右不对称的遗传途径;帮助揭示了导致肢体背腹模式形成的途径;为我们理解骨骼形态发生做出了贡献,并确定了可能是达尔文雀喙多样化基础的发育机制。尽管身为哈佛大学遗传学教授,塔宾却说:“我这辈子从未做过一次遗传学实验!”。随着他最新的项目——墨西哥洞穴鱼的遗传学研究,这种情况正在改变。2007年10月3日,我在塔宾位于哈佛的办公室对他进行了采访。

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