并可导致诸如神经学疾病、糖尿病跟免疫学疾病等的产生

今年诺贝尔生理学或医学奖的获奖者中James E. Rothman, Randy W. Schekman此前获得了2002年的拉斯克奖,而Thomas C.Südhof也获得了今年的基本医学研究奖,分辨来自耶鲁大学、加州伯克利大学和斯坦福大学。

从左到右,顺次为James E. Rothman,Randy W. Schekman和Thomas C. Südhof

三人简介

James E. Rothman于1950年诞生于美国麻省Haverhill,1976年从哈佛医学院取得博士学位,曾在MIT做过博后。1978年他进入斯坦福大学,开端了对细胞囊泡的研究。他曾任职的研究机构还包含普林斯顿大学、留念斯隆-凯特灵癌症研讨所跟哥伦比亚大学。2008年,他参加耶鲁大学,目前为该校教学和细胞学系主席。

Randy W. Schekman于1948年出身于美国明尼苏达州St Paul,曾就学于加州大学洛杉矶分校和斯坦福大学,1974年从斯坦福大学失掉博士学位,导师为1959年诺奖得主Arthur Kornberg,所在院系恰是多少年后Rothman加入的系。1976年,Schekman加入加州大学伯克利分校,目前为该校分子与细胞学系传授。他同时也是霍华德•休斯医学研究院研究职员。

Thomas C. Südhof于1955年出生于德国Göttingen,他曾就学于哥廷根大学,1982年从该校获得MD学位并于同年获得该校神经化学博士学位。1983年,他加入美国德州大学西南医学核心,作为Michael Brown和Joseph Goldstein的博后(Joseph Goldstein于1985年获得诺贝尔生理学或医学奖)。Südhof于1991年成为霍华德•休斯医学研究院研究人员,2008年景为斯坦福大学分子与细胞生理学教授。

获奖理由

Randy Schekman发明了囊泡传输所需的一组基因;James Rothman说明了囊泡是如何与目的融会并传递的蛋白质机器;Thomas Südhof则揭示了信号是如何领导囊泡准确开释被运输物的。

通过研究,Rothman, Schekman和Südhof揭开了细胞物资运输和送达的精确把持体系的面纱。该系统的失调会带来有害影响,并可导致诸如神经学疾病、糖尿病和免疫学疾病等的产生。

诺贝尔奖官方宣布的获奖理由

Traffic congestion reveals genetic controllers

Randy Schekman was fascinated by how the cell organizes its transport system and in the 1970s decided to study its genetic basis by using yeast as a model system. In a genetic screen, he identified yeast cells with defective transport machinery, giving rise to a situation resembling a poorly planned public transport system. Vesicles piled up in certain parts of the cell. He found that the cause of this congestion was genetic and went on to identify the mutated genes. Schekman identified three classes of genes that control different facets of the cell´s transport system, thereby providing new insights into the tightly regulated machinery that mediates vesicle transport in the cell.

Docking with precision

James Rothman was also intrigued by the nature of the cell´s transport system. When studying vesicle transport in mammalian cells in the 1980s and 1990s, Rothman discovered that a protein complex enables vesicles to dock and fuse with their target membranes. In the fusion process, proteins on the vesicles and target membranes bind to each other like the two sides of a zipper. The fact that there are many such proteins and that they bind only in specific combinations ensures that cargo is delivered to a precise location. The same principle operates inside the cell and when a vesicle binds to the cell´s outer membrane to release its contents.

It turned out that some of the genes Schekman had discovered in yeast coded for proteins corresponding to those Rothman identified in mammals, revealing an ancient evolutionary origin of the transport system. Collectively, they mapped critical components of the cell´s transport machinery.

Timing is everything

Thomas Südhof was interested in how nerve cells communicate with one another in the brain. The signalling molecules, neurotransmitters, are released from vesicles that fuse with the outer membrane of nerve cells by using the machinery discovered by Rothman and Schekman. But these vesicles are only allowed to release their contents when the nerve cell signals to its neighbours. How is this release controlled in such a precise manner? Calcium ions were known to be involved in this process and in the 1990s, Südhof searched for calcium sensitive proteins in nerve cells. He identified molecular machinery that responds to an influx of calcium ions and directs neighbour proteins rapidly to bind vesicles to the outer membrane of the nerve cell. The zipper opens up and signal substances are released. Südhof´s discovery explained how temporal precision is achieved and how vesicles´ contents can be released on command.

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