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  孤独的领域


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“Eduardo Moreno通过第一次选择,因为他那强有力的纪录,并通过最后一轮,这归功于他的创新性,但具有很强针对性的科研经费,”欧洲研究委员会陪审团主席Susan Gasser写道。

对于一个成功的职业生涯,一个普遍而又明智的策略,就是使你的研究兴趣与科学界认为是热点且大有希望的想法结合起来。但有时有远见就足够了。当37岁的西班牙语发育生物学家Eduardo Moreno 打算为一种困惑科学家们30年的现象作解释时,那当然无异于进行一场赌博。

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今年年初,经过Morena所谓的“三年来实施一个几乎没有一个西班牙赞助机构里的人看好的项目”,当他一个充满竞争的科研经费申请中接到来自欧洲研究委员会一百万欧元的奖金时,这场赌博胜利了,“我很高兴结识一些欧洲最优秀的科学家,”Moreno说。

先工作,后娱乐

生在一个律师家庭里,Moreno在和朋友玩显微镜和化学试剂盒时初次尝到科学的滋味。“这再街坊邻里是一件很大的事,”他回忆道。后来,当他还是个化学专业的本科生,且发现了自己的激情,他参加了在马德里自治大学开办的发育生物学招待会。“我很着迷,我发现原来动物体是按规律构建起来的,”他说。

Moreno加入了Ginés Morata在马德里Severo Ochoa分子生物学中心的实验室,在他攻读博士学位的早期,他所遇到的一个称为细胞竞争的现象,即“其中一种细胞型启动,其他细胞型就无法形成身体的一部分,”Moreno形容道。从Moreno和他的同事报告这一观察结果已经三十年过去了,但“具体是怎样一个过程很含糊,有些人不相信这个结果”。 Morata 建议Moreno为获得博士学位搜集一些坚实的数据,然后再继续这个冒险的项目,Moreno回忆道。

Moreno的第一份工作是在实验室帮助一个博士后寻找诱变技术,以确定参与器官发育和定位的新基因,这使得他以第二作者出现在一篇发表在《科学》杂志论文,就在他开始攻读博士学位不久。后来,他专心研究其中一个新发现的基因,即尾椎基因,并记录了它在苍蝇臀部形成过程的作用,结果又发表一篇论文,这一次是在《自然》杂志上,且是第一作者。这工作不仅为他赢得了博士学位,还有两项重要奖项,来自马德里自治大学的特别奖和西班牙生物化学与分子生物学领域的innogenetics青年科学家奖。

娱乐时间

当Moreno收集完有关尾椎基因的资料,距离5年的博士生涯结束还有一年半,“按今天的研究进度,几年的四处游玩真是一种奢侈,”他说。对于博士学位他胜券在握,他说于是他开始研究细胞竞争“是否可以用现代遗传学方法来研究和解释”。

在那一年,和随后几年在Morata的实验室作博士后(后来与Konrad Basler一起在瑞士的苏黎世大学),Moreno能够将以前细胞的竞争孤立现象与良好建立的程序性细胞死亡联系起来,他假设正常细胞能够发育过程中识别次优细胞,并迫使他们“大量死亡,像细胞群中的一个生态系统,”他说。他在瑞士证明了该假设,又发表了一篇作为第一作者的论文(《自然》杂志上),这使得他赢得了Severo Ochoa分子生物学中心的一个奖项,以及Charles Rodolphe Brupbacher基金会的青年研究员奖。

Moreno还发现了一个参与细胞竞争的人类癌症基因的同源基因,他表明,该基因只要被启动,就会把正常细胞转变为“超级竞争者:可以使周围细胞认为它们是坏的而且即将死亡的细胞”。

 

冒险的想法

Moreno回想起2005年在马德里的西班牙国家癌症研究中心(CNIO)当5年的新生辅导,启动CNIO资金,Caja MadridMutua Madrile?a “让我能够做研究,并有相当大的七人组,”他说。

为了让自己成为一个独立的科学家,他必须想办法获取资助,西班牙科学部是明显的来源。但他的资助申请被驳回;审判官声称他太没有经验而不足以承担如此宏大的项目。然后,它再一次被否决,一次又一次。 “对我来说,它成为个人的事情,我真的想要这个项目,而我… 不断的递出申请,希望科学部认识到他们的错误,”他说。

对信心——投资——的支持,Moreno终于从一个不太可能的来源找到:欧洲研究委员会(E R C)。在其中一个欧洲历史最具竞争力的科研经费申请中,Moreno夺得了一个ERC的开始独立研究员经费,共1百万欧元,来资助他未来5年的研究。“我们有720个申请者竞争18种资助;换句话说,只有2-3 %得到资助,” Susan Gasser在一封给《科学生涯》的信中写道。她是欧洲研究委员会陪审团主席,负责作出裁决。“Eduardo Moreno通过第一次选择,因为他那强有力的纪录,并通过最后一轮,这归功于他的创新性,但具有很强针对性的科研经费,和他的令人信服的报告”。

 

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"Eduardo Moreno made it through the first selection because of his strong past record and made it through the last round thanks to the innovative, yet highly relevant, nature of his grant," writes ERC jury panel chair Susan Gasser.

A common and sensible strategy for a successful career is to align your research interests with ideas the scientific community thinks are hot and promising. But sometimes a long shot really pays off. When Spanish developmental biologist Eduardo Moreno, 37, set to provide an explanation for an observation that had puzzled scientists for 30 years, he certainly was taking a gamble.
Earlier this year, after what Morena calls "3 years of carrying on a project that almost nobody within the Spanish funding agencies believed in," the gamble paid off when he received an award of 1 million from the European Research Council in a highly competitive research funding call. "I was very happy to get some validation by the best scientists of Europe," Moreno says.

Work first, play later

Born to a family of lawyers, Moreno explored an early taste for science playing with microscopes and chemistry kits with friends. "It was a big thing in the neighborhood," he recalls. Later, he attended a development biology conference at the Universidad Autónoma de Madrid while he was a biochemistry undergrad and discovered his passion. "I was fascinated that there were rules to construct the body of animals," he says.
Moreno joined the lab of Ginés Morata at the Severo Ochoa Molecular Biology Centre in Madrid. Early in his Ph.D., he encountered a phenomenon called cell competition whereby "one of the cell types start[s] not allowing the other cell type to form part of the body," as Moreno puts it. Thirty years had passed since Morata and colleagues had reported the observation, but "it was very obscure what was going on there. Some people didn't believe [in] it." Morata advised Moreno to gather some solid data for a Ph.D. before taking on such a risky project, Moreno recalls.

Moreno's first job in the lab--helping a postdoc develop a mutagenesis technique to identify new genes involved in organ development and positioning--earned him a second-author paper in Science just a couple of years into his Ph.D. He then focused on one of those newly discovered genes, the caudal gene, and documented its role in the formation of the fly's posterior. Another paper resulted, this one in Nature, and this one with Moreno as first author. The work earned Moreno his Ph.D.--but not just yet--along with two important awards, the Extraordinary Award from the Universidad Autónoma de Madrid, and the Innogenetics Young Scientists' Award from the Spanish Society for Biochemistry and Molecular Biology.

 

Just Trans!

Play time

When Moreno finished gathering data on the caudal gene, he still had a year and a half before the official completion of his 5-year Ph.D. "The pace that research goes today, it's almost a luxury to have a couple of years to play around," he says. His Ph.D. secure, he says he set out to see if cell competition "was a topic we could study with modern genetics methods and explain it."
During that year, and subsequent years spent as a postdoc in Morata's lab (and later with Konrad Basler at the University of Zurich, Switzerland), Moreno was able to link the previously isolated phenomenon of cell competition to the well-established process of programmed cell death. He hypothesized that normal cells were able to recognize suboptimal cells during development and force them to die, "a lot like an ecological system in a population of cells," he says. He proved the hypothesis in Switzerland and published another first-author paper (this one in Nature). The result won him a prize from the Severo Ochoa Molecular Biology Centre and the Young Investigator Award from the Charles Rodolphe Brupbacher Foundation.
Moreno also found a homologue of a human cancer gene involved in cell competition. He demonstrated that, when activated, this gene could transform regular cells into "supercompetitors: cells that … are able to make the surrounding cells believe that they are bad cells and … [need] to die."

A risky idea

Moreno was pulled back to Spain in 2005 by a 5-year junior-leader position at the Spanish National Cancer Research Centre (CNIO) in Madrid. Start-up funding from CNIO, Caja Madrid, and Mutua Madrile?a "allowed me to do research and have a relatively big group of seven persons," he says.
To establish himself as an independent scientist, he had to attract grant money, and the Spanish Ministry for Science was the obvious source. But his grant application to the Spanish ministry was rejected; the judges claimed the he was too inexperienced to take on such an ambitious project. Then it was rejected again, and again, and again. "For me, it became personal. I really wanted this project, and I … kept sending it in the hope [the ministry] would realize their mistake," he says.
The vote of confidence--and investment--Moreno sought eventually came from a less likely source: the European Research Council (ERC). In one of the most competitive funding calls of European history, Moreno won an ERC Starting Independent Researcher Grant, worth 1 million, to fund his research during the next 5 years. "We had 720 applicants to our panel for 18 grants; in other words, only 2-3% got funded," writes Susan Gasser, chair of the ERC jury panel that made the award, in an e-mail to Science Careers. "Eduardo Moreno made it through the first selection because of his strong past record and made it through the last round thanks to the innovative, yet highly relevant, nature of his grant, and his compelling presentation of his ideas."

 

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