由顏寧《一份失敗的基金申請》看基金申請主意事項
欄目:最新研究動態 發布時間:2019-05-22
顏寧在2014年發布博文《一份失敗的基金申請》,文中公布的評審意見中一些負面評價如下......

《堡垒之夜》腾讯手游 www.qkdwy.icu 顏寧在2014年發布博文《一份失敗的基金申請》,

鏈接地址://blog.sciencenet.cn/blog-65865-824367.html

 

文中公布的評審意見中一些負面評價如下:

(海外評議)到目前為止還沒有真核葡萄糖轉運蛋白GLUTs的晶體結構。申請人在原核同原膜蛋白XylE FucP的結構基礎上解析GLUTs和突變體的結構,解析其轉運機理。這應是非常前沿的研究,科研環境一流,申請人非常出色。但是有幾個薄弱點限制了這份申請書的前景。
第一,申請者還沒有任何數據來說明怎樣來獲得足夠的結晶用蛋白。

第二,申請者沒有引入任何創新的方法來制備真核膜蛋白。

第三,申請人也沒有具體的辦法來解決傳統晶體生長失敗后怎么辦。

 

不足之處有兩點: 1)研究方案的描述過于簡化,沒有說明哪幾種真核GLUTs將用于表達純化;如何進行分子動力學模擬,和誰合作等等 2)沒有前期工作顯示哪一種GLUTs可以表達、純化。但鑒于申請人在原核膜蛋白結構生物學領域的強勁實力,相信她可以把過去成功的經驗運用到這個課題上, 并取得突破性進展。 因此建議資助。
. 葡萄糖跨膜轉運已經有很長的研究歷史,葡萄糖轉運蛋白GLUTs也得到非常廣泛的研究,但目前對GLUTs認識仍停留在生化和細胞水平,對其結構的認識依然是一個空缺,是當前結構生物領域期待獲得的目標之一。當前膜蛋白結構的研究非?;郝?,主要原因是純膜蛋白的獲取和結晶存在著技術瓶頸。因此該申請項目具有難度大,挑戰高的特點。關于GLUTs結構的研究,申請人沒有提供足夠的初步數據。

二.申請人在膜轉運蛋白結構和機理方面有很好的研究工作基礎,具有較高的學術水平,已經成功解析了多個膜轉運蛋白和通道蛋白的三維結構。


三.解析膜蛋白的晶體結構意義雖然重大,但屬于高難度,高挑戰性的項目。申請人沒有提供關于獲得GLUTs蛋白之類的初步數據。

可見,即使在本領域有突出貢獻的牛人,在基金申請上也需多花心思,包括數據準備和基金撰寫。顏寧的研究基礎和項目創新性自然不用懷疑,但可能鑒于一些重點數據尚不便公開,導致審稿專家認為其 “研究方案的描述過于簡化”、“還沒有任何數據來說明怎樣來獲得足夠的結晶用蛋白”。

 

對于多數研究者來說,數據還沒達到“不便公開給審稿專家看”的等級,這一點我們是否該慶幸
image.png

 

由此可見,前期預實驗提供充足的數據,證明假說的可行性有多重要。 另外,標書撰寫時,一定要注意交代一些關鍵技術,如,如何獲得某某細胞, 如何構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.

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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.