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罗伯特・尼科威

以表彰他多年来对於 GPCR (G-蛋白质偶合接受体) 的关键性的贡献。此贡献对於寻找有效的药品提供了极重要的新思路。

贡献

生物体内有某种细胞藉著释放化学物质,传递到其他细胞,以控制他们的行为。这些化学物质可控制生命中重要的过程,诸如脑功能、心脏泵血及生殖等等现象。罗伯特・尼科威教授(Professor Robert Lefkowitz)从事这方面研究达三十五年,揭示了这些化学信号如何被细胞接受和表达的奥秘。其关键在於受体细胞膜表面具有一组G-蛋白偶联受体(GPCR)。GPCR与其他受体不同,来回穿膜七次,又称七次穿膜受体。在1970年代,尼科威教授开始设法分离这种受体及鉴定其结构,当时七次穿膜受体仍是个理论的概念。在1986年尼科威教授和Merck Sharp 和 Dohme研究所的同事合作,分离了第一个这类受体的基因并阐明它的初级蛋白结构,是一项重要突破。从此尼科威教授和其他科学家,努力不懈,陆续发现上百种这类受体,不同受体各有分工,针对特有的化学信号。尼科威教授更进一步发现,这类受体并不是一直激活的,他们传递信息后,就被另一种反馈机制沈默,以防止过度的刺激。在研究反馈机制的过程中,尼科威教授又发现一类新蛋白。他们不但能沈默受体,且在生理上有重要的功能,例如控制细胞的生长和分化。许多科学家从事有关信号传递的研究,各有贡献,但尼科威教授却首创先河,一直领先。许多沿用已久的药物,能有效治病,但人们知其然而不知其所以然;经过尼科威教授的研究,制药公司现在才进一步了解,这些药物如何控制疾病。这些药物包括用於高血压和心脏衰竭的β-阻断剂(如propronolol);医治胃溃疡的H2拮抗剂(如cimetidine);医治过敏症的H1拮抗剂(如chlorpheniramine)和治疗精神分裂症的多巴胺拮抗剂(如clozapine)。利用这方面的知识,药厂可以寻找更多新药物,针对这类G-蛋白偶联受体,来治疗各种疾病。

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得奖人获奖介绍

The human body is made up of many different types of tissues and many different kinds of cells. To co-ordinate body functions, cells signal to other cells in the same organ and in different organs by releasing chemical messengers that travel through the bloodstream. The chemical messengers control all of the vital body processes. For example, they determine the force of a heartbeat and the number of beats per minute, the height of the blood pressure, and the propulsive energy of the intestine. In the brain these chemicals profoundly influence our moods and our behavior, including our drives for food and sex. When Lefkowitz began his work in the late 1960’s, scientists had already identified several chemical messengers but they did not know how these chemicals affected the target cells so as to alter their behavior. Over the subsequent 35 years Lefkowitz and his students painstakingly elucidated a family of molecules on the surface of target cells that receive the chemical messages. These receiving molecules are known as G protein-coupled receptors (GPCRs).

GPCRs are proteins embedded in the surface membrane of target cells with their receiving ends facing the outside fluid. Each cell produces many different GPCRs, each tuned to respond to different chemical messengers. For example, certain GPCRs called beta-adrenergic receptors located on heart muscle cells recognize adrenalin secreted by the adrenal gland and thereby control the heartbeat. When a human is physically threatened, the adrenal gland releases adrenalin which travels through the bloodstream and attaches to beta-adrenergic receptors on heart muscle. Once stimulated by the adrenalin, the receptors initiate a cascade of events that causes the heart to beat stronger and faster. This prepares the threatened person for “fight or flight”.

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得奖者简介
罗伯特・尼科威

罗伯特・尼科威 (Robert Lefkowitz) (1943年出生) 现任美国霍华德.休斯研究所研究员,美国北卡罗来纳州杜克大学医学中心詹姆斯杜克医学教授和生物化学教授。

尼科威教授在英国出生,早年於纽约哥伦比亚学院主修化学,於1962年取得学士学位,复於1966年取得哥伦比亚大学内外科医生学院医学博士。他获选为美国科学院和美国艺术及科学院院士。

得奖人自传
得奖者特写
2007年度邵逸夫生命科学与医学奖讲座