由颜宁《一份失败的基金申请》看基金申请主意事项
栏目:最新研究动态 发布时间:2018-11-26
颜宁在2014年发布博文《一份失败的基金申请》,文中公布的评审意见中一些负面评价如下......

颜宁在2014年发布博文《一份失败的基金申请》,

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

 

文中公布的评审意见中一些负面评价如下:

(海外评议)到目前为止还没有真核葡萄糖转运蛋白GLUTs的晶体结构。申请人在原核同原膜蛋白XylE FucP的结构基础上解析GLUTs和突变体的结构,解析其转运机理。这应是非常前沿的研究,科研环境一流,申请人非常出色。但是有几个薄弱点限制了这份申请书的前景。
第一,申请者还没有任何数据来说明怎样来获得足够的结晶用蛋白。

第二,申请者没有引入任何创新的方法来制备真核膜蛋白。

第三,申请人也没有具体的办法来解决传统晶体生长失败后怎么办。

 

不足之处有两点: 1)研究方案的描述过于简化,没有说明哪几种真核GLUTs将用于表达纯化;如何进行分子动力学模拟,和谁合作等等 2)没有前期工作显示哪一种GLUTs可以表达、纯化。但鉴于申请人在原核膜蛋白结构生物学领域的强劲实力,相信她可以把过去成功的经验运用到这个课题上, 并取得突破性进展。 因此建议资助。
. 葡萄糖跨膜转运已经有很长的研究历史,葡萄糖转运蛋白GLUTs也得到非常广泛的研究,但目前对GLUTs认识仍停留在生化和细胞水平,对其结构的认识依然是一个空缺,是当前结构生物领域期待获得的目标之一。当前膜蛋白结构的研究非常缓慢,主要原因是纯膜蛋白的获取和结晶存在着技术瓶颈。因此该申请项目具有难度大,挑战高的特点。关于GLUTs结构的研究,申请人没有提供足够的初步数据。

二.申请人在膜转运蛋白结构和机理方面有很好的研究工作基础,具有较高的学术水平,已经成功解析了多个膜转运蛋白和通道蛋白的三维结构。


三.解析膜蛋白的晶体结构意义虽然重大,但属于高难度,高挑战性的项目。申请人没有提供关于获得GLUTs蛋白之类的初步数据。

可见,即使在本领域有突出贡献的牛人,在基金申请上也需多花心思,包括数据准备和基金撰写。颜宁的研究基础和项目创新性自然不用怀疑,但可能鉴于一些重点数据尚不便公开,导致审稿专家认为其 “研究方案的描述过于简化”、“还没有任何数据来说明怎样来获得足够的结晶用蛋白”。

 

对于多数研究者来说,数据还没达到“不便公开给审稿专家看”的等级,这一点我们是否该庆幸
image.png

 

由此可见,前期预实验提供充足的数据,证明假说的可行性有多重要。 另外,标书撰写时,一定要注意交代一些关键技术,如,如何获得某某细胞, 如何构建某某模型一定要交代清楚。

 

最后,再分享一下颜宁推荐的科研金点子:

 

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.

Top of page

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.