由顏寧《一份失敗的基金申請(qǐng)》看基金申請(qǐng)主意事項(xiàng)
顏寧在2014年發(fā)布博文《一份失敗的基金申請(qǐng)》，
鏈接地址：http://blog.sciencenet.cn/blog-65865-824367.html
文中公布的評(píng)審意見中一些負(fù)面評(píng)價(jià)如下：
(海外評(píng)議）到目前為止還沒有真核葡萄糖轉(zhuǎn)運(yùn)蛋白GLUTs的晶體結(jié)構(gòu)。申請(qǐng)人在原核同原膜蛋白XylE 和 FucP的結(jié)構(gòu)基礎(chǔ)上解析GLUTs和突變體的結(jié)構(gòu)，解析其轉(zhuǎn)運(yùn)機(jī)理。這應(yīng)是非常前沿的研究，科研環(huán)境一流，申請(qǐng)人非常出色。但是有幾個(gè)薄弱點(diǎn)限制了這份申請(qǐng)書的前景。
第一，申請(qǐng)者還沒有任何數(shù)據(jù)來說明怎樣來獲得足夠的結(jié)晶用蛋白。
第二，申請(qǐng)者沒有引入任何創(chuàng)新的方法來制備真核膜蛋白。
第三，申請(qǐng)人也沒有具體的辦法來解決傳統(tǒng)晶體生長(zhǎng)失敗后怎么辦。
不足之處有兩點(diǎn)： （1）研究方案的描述過于簡(jiǎn)化，沒有說明哪幾種真核GLUTs將用于表達(dá)純化；如何進(jìn)行分子動(dòng)力學(xué)模擬，和誰合作等等 （2）沒有前期工作顯示哪一種GLUTs可以表達(dá)、純化。但鑒于申請(qǐng)人在原核膜蛋白結(jié)構(gòu)生物學(xué)領(lǐng)域的強(qiáng)勁實(shí)力，相信她可以把過去成功的經(jīng)驗(yàn)運(yùn)用到這個(gè)課題上， 并取得突破性進(jìn)展。 因此建議資助。
一. 葡萄糖跨膜轉(zhuǎn)運(yùn)已經(jīng)有很長(zhǎng)的研究歷史，葡萄糖轉(zhuǎn)運(yùn)蛋白GLUTs也得到非常廣泛的研究，但目前對(duì)GLUTs認(rèn)識(shí)仍停留在生化和細(xì)胞水平，對(duì)其結(jié)構(gòu)的認(rèn)識(shí)依然是一個(gè)空缺，是當(dāng)前結(jié)構(gòu)生物領(lǐng)域期待獲得的目標(biāo)之一。當(dāng)前膜蛋白結(jié)構(gòu)的研究非常緩慢，主要原因是純膜蛋白的獲取和結(jié)晶存在著技術(shù)瓶頸。因此該申請(qǐng)項(xiàng)目具有難度大，挑戰(zhàn)高的特點(diǎn)。關(guān)于GLUTs結(jié)構(gòu)的研究，申請(qǐng)人沒有提供足夠的初步數(shù)據(jù)。
二．申請(qǐng)人在膜轉(zhuǎn)運(yùn)蛋白結(jié)構(gòu)和機(jī)理方面有很好的研究工作基礎(chǔ)，具有較高的學(xué)術(shù)水平，已經(jīng)成功解析了多個(gè)膜轉(zhuǎn)運(yùn)蛋白和通道蛋白的三維結(jié)構(gòu)。
三．解析膜蛋白的晶體結(jié)構(gòu)意義雖然重大，但屬于高難度，高挑戰(zhàn)性的項(xiàng)目。申請(qǐng)人沒有提供關(guān)于獲得GLUTs蛋白之類的初步數(shù)據(jù)。
可見，即使在本領(lǐng)域有突出貢獻(xiàn)的牛人，在基金申請(qǐng)上也需多花心思，包括數(shù)據(jù)準(zhǔn)備和基金撰寫。顏寧的研究基礎(chǔ)和項(xiàng)目創(chuàng)新性自然不用懷疑，但可能鑒于一些重點(diǎn)數(shù)據(jù)尚不便公開，導(dǎo)致審稿專家認(rèn)為其 “研究方案的描述過于簡(jiǎn)化”、“還沒有任何數(shù)據(jù)來說明怎樣來獲得足夠的結(jié)晶用蛋白”。
對(duì)于多數(shù)研究者來說，數(shù)據(jù)還沒達(dá)到“不便公開給審稿專家看”的等級(jí)，這一點(diǎn)我們是否該慶幸…
由此可見，前期預(yù)實(shí)驗(yàn)提供充足的數(shù)據(jù)，證明假說的可行性有多重要。 另外，標(biāo)書撰寫時(shí)，一定要注意交代一些關(guān)鍵技術(shù)，如，如何獲得某某細(xì)胞, 如何構(gòu)建某某模型一定要交代清楚。
最后，再分享一下顏寧推薦的科研金點(diǎn)子：
Scientist: Four golden lessons
Steven Weinberg1
When I received my undergraduate degree — about a hundred years ago — the physics literature seemed to me a vast, unexplored ocean, every part of which I had to chart before beginning any research of my own. How could I do anything without knowing everything that had already been done? Fortunately, in my first year of graduate school, I had the good luck to fall into the hands of senior physicists who insisted, over my anxious objections, that I must start doing research, and pick up what I needed to know as I went along. It was sink or swim. To my surprise, I found that this works. I managed to get a quick PhD — though when I got it I knew almost nothing about physics. But I did learn one big thing: that no one knows everything, and you don't have to.
Another lesson to be learned, to continue using my oceanographic metaphor, is that while you are swimming and not sinking you should aim for rough water. When I was teaching at the Massachusetts Institute of Technology in the late 1960s, a student told me that he wanted to go into general relativity rather than the area I was working on, elementary particle physics, because the principles of the former were well known, while the latter seemed like a mess to him. It struck me that he had just given a perfectly good reason for doing the opposite. Particle physics was an area where creative work could still be done. It really was a mess in the 1960s, but since that time the work of many theoretical and experimental physicists has been able to sort it out, and put everything (well, almost everything) together in a beautiful theory known as the standard model. My advice is to go for the messes — that's where the action is.
My third piece of advice is probably the hardest to take. It is to forgive yourself for wasting time. Students are only asked to solve problems that their professors (unless unusually cruel) know to be solvable. In addition, it doesn't matter if the problems are scientifically important — they have to be solved to pass the course. But in the real world, it's very hard to know which problems are important, and you never know whether at a given moment in history a problem is solvable. At the beginning of the twentieth century, several leading physicists, including Lorentz and Abraham, were trying to work out a theory of the electron. This was partly in order to understand why all attempts to detect effects of Earth's motion through the ether had failed. We now know that they were working on the wrong problem. At that time, no one could have developed a successful theory of the electron, because quantum mechanics had not yet been discovered. It took the genius of Albert Einstein in 1905 to realize that the right problem on which to work was the effect of motion on measurements of space and time. This led him to the special theory of relativity. As you will never be sure which are the right problems to work on, most of the time that you spend in the laboratory or at your desk will be wasted. If you want to be creative, then you will have to get used to spending most of your time not being creative, to being becalmed on the ocean of scientific knowledge.
Finally, learn something about the history of science, or at a minimum the history of your own branch of science. The least important reason for this is that the history may actually be of some use to you in your own scientific work. For instance, now and then scientists are hampered by believing one of the over-simplified models of science that have been proposed by philosophers from Francis Bacon to Thomas Kuhn and Karl Popper. The best antidote to the philosophy of science is a knowledge of the history of science.
More importantly, the history of science can make your work seem more worthwhile to you. As a scientist, you're probably not going to get rich. Your friends and relatives probably won't understand what you're doing. And if you work in a field like elementary particle physics, you won't even have the satisfaction of doing something that is immediately useful. But you can get great satisfaction by recognizing that your work in science is a part of history.
Look back 100 years, to 1903. How important is it now who was Prime Minister of Great Britain in 1903, or President of the United States? What stands out as really important is that at McGill University, Ernest Rutherford and Frederick Soddy were working out the nature of radioactivity. This work (of course!) had practical applications, but much more important were its cultural implications. The understanding of radioactivity allowed physicists to explain how the Sun and Earth's cores could still be hot after millions of years. In this way, it removed the last scientific objection to what many geologists and paleontologists thought was the great age of the Earth and the Sun. After this, Christians and Jews either had to give up belief in the literal truth of the Bible or resign themselves to intellectual irrelevance. This was just one step in a sequence of steps from Galileo through Newton and Darwin to the present that, time after time, has weakened the hold of religious dogmatism. Reading any newspaper nowadays is enough to show you that this work is not yet complete. But it is civilizing work, of which scientists are able to feel proud.
1. Department of Physics, the University of Texas at Austin, Texas 78712, USA. This essay is based on a commencement talk given by the author at the Science Convocation at McGill University in June 2003.