介绍:
Telephone Interview with Joachim Frank
Telephone interview with Joachim Frank following the announcement of the 2017 Nobel Prize in Chemistry on 4 October 2017. The interviewer is Adam Smith, Chief Scientific Officer of Nobel Media.
[Joachim Frank] Hello.
[Adam Smith] Oh, hello. My name is Adam Smith, calling from Nobelprize.org, the website of the Nobel Prize in Stockholm. Congratulations on the award of the Nobel Prize.
[Joachim Frank] Oh, thank you very much.
[Adam Smith] Göran Hansson mentioned that he woke you up with his phone call.
[Joachim Frank] Yeah, although it’s…it’s sort of a race because we have a new dog and…and she wakes up very early in the morning. So this time, it was the Nobel Prize! [Laughs] Normally, normally, it’s the dog that wakes us up.
[Adam Smith] That’s nice because that will ground you today. While everything else is rushing around, she’s still ...
[Joachim Frank] [Laughs]
[Adam Smith] The Committee have singled out the fact that you developed the image analysis methods to allow ensembles of biomolecules to be put together and produce 3D images from many 2D images. You’re interested in images generally. You’re a photographer, I know. Is there something special about the way you view images that allowed you to do it, do you think?
[Joachim Frank] I don’t know I’m just, I’m just very visually oriented. So I see patterns, I see structures, I see…I see patterns very, very fast in a background and so forth. So I have a view when I walk around, sometimes I take pictures. You know, I’ve had photographs in exhibitions and so forth.
[Adam Smith] Yes, indeed. And… was there one moment where you suddenly realised how to put these ensembles together?
[Joachim Frank] Well, regarding the three-dimensional reconstruction, first of all, the whole step of averaging, that was one step. But these are two-dimensional averages and…and how to get to three-dimensions requires two steps. One was to find relative orientations between the molecules, which is difficult if you don’t know the structure. So it’s like a chicken-and-egg problem.
[Adam Smith] Yeah.
[Joachim Frank] And the other one is putting all that information together once you know the angles. So these are essentially different moments, so, in terms of how to find the orientations, there was an ‘aha moment’ in 1977 or something like this where I conceived of the…the random conical method.
[Adam Smith] What does this technique allow us to see that we haven’t seen before?
[Joachim Frank] Well, we now are able to see molecules in their free unconstrained functional states. If you have a molecule and you have a system in vitro in which you have all these different ligands and all the factors present; if you have a system in which the molecule actually can perform work, these systems exist, for instance, for the ribosome, you can do in vitro translation of…of a messenger RNA, if all the different ingredients are there. Or you can do, you know, something like transcription, all this. But you have molecular machines, and there you have…have a certain work cycle. Now, the x-ray approach would be to, you know, try to get a…a particular state in…in a crystalline form. And…and so that would be one of the many states. And you don’t even know whether this is an important state; whether it’s very populated, because in forming a crystal, you’re imposing some energy constraints. You want to minimise the energy of aggregating the molecules that has nothing to do with the functional conformation. Whereas in cryo-EM, the molecules are actually there, they are frozen in the process of doing their thing. And since we have the capability of classifying all the views that exist in the same sample and extract all the corresponding three-dimensional images, we have…we have a whole inventory of…of the molecular machine in its various states, and then we can connect them in some kind of a narrative.
[Adam Smith] Yes, you’re capturing it behaving naturally.
[Joachim Frank] Yes, yes. So that’s the important distinction.
[Adam Smith] Lovely, thank you. Beautifully said. Now, I’ll let you go but just one thing. Because you’re a photographer, is there a possibility, do you think, that somebody around you or yourself could take a photograph and send it to me for Nobelprize.org? Possibly with your new dog?
[Joachim Frank] I do have…I do have a great image which…which…actually has to do with…We were in Central Park and I took a picture of the dog sitting…sitting there and it was illuminated from…from the back, in a…in a sunlit place, and…and one sees the projection of the dog on the ground and me photographing the dog, also.
[Adam Smith] That would be absolutely splendid.
[Joachim Frank] So this is…this is a fantastic illustration of, you know, 3D, 2D, projections and so on. Yeah.
[Adam Smith] The whole Nobel Prize in one picture.
[Joachim Frank] Yes, yes. [Laughs]
[Adam Smith] So, we look forward to welcoming you to Stockholm in December. You will be coming, I hope?
[Joachim Frank] Yes, yes, I’ll be coming with…with my family.
[Adam Smith] Lovely. Well, we look forward to the celebration. Thank you very much for speaking to me.
[Joachim Frank] Thank you.
[Adam Smith] Thank you. Bye.
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