[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 of the award of the Nobel Prize.
JF: Oh thank you very much.
AS: Göran Hansson mentioned that he woke you up with his phone call.
JF: Yeah, although it’s, it’s sort of a race because we have a new dog and she wakes
up very early in the morning.
So this time it was the Nobel prize!
[Laughs] Normally it’s the dog that wakes us up.
AS: That’s nice because that will ground you today.
While everything else is rushing around she’s still ..
JF: [Laughs]
AS: 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?
JF: I don’t know I’m just, I’m just very visually oriented.
So I see patterns, I see structures, 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.
I’ve had photographs in exhibitions and so forth.
AS: Yes indeed.
Was there one moment where you suddenly realised how to put these ensembles together?
JF: 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 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.
AS: Yeah.
JF: 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 random
conical method.
AS: What does this technique allow us to see that we haven’t seen before?
JF: 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 a messenger RNA if all the different ingredients are there.
Or you can do something like transcription, all this.
But you have molecular machines, and there you have a certain work cycle.
Now the x-ray approach would be to try to get a particular state in a crystalline form.
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 3-dimensional images we have a whole inventory of the molecular
machine in its various states, and then we can connect them in some kind of a narrative.
AS: Yes you’re capturing it behaving naturally.
JF: Yes, yes.
So that’s the important distinction.
AS: 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?
JF: I do have a great image which actually has to do with…
We were in Central Park and I took a picture of the dog sitting there and it was illuminated
from the back, in a sunlit place, and one sees the projection of the dog on the ground.
And me photographing the dog also.
AS: That would be absolutely splendid.
JF: So this is a fantastic illustration of 3D, 2D, projections and so on.
AS: The whole Nobel Prize in one picture.
JF: Yes, yes.
[Laughs]
AS: So we look forward to welcoming you to Stockholm in December.
You will be coming I hope.
JF: Yes I’ll be coming with my family.
AS: Lovely.
Well we look forward to the celebration.
Thank you very much for speaking to me.
JF: Thank you.
AS: Thank you.
bye