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2012 Nobel prize laureate Brian Kobilka about G protein-coupled receptors, communication and competition.


Nachrichten aus der Chemie: Professor Kobilka, everyone agrees that you very much like to keep a low profile. Then yesterday you had to deliver the opening lecture here at the Lindau Nobel Laureate Meeting. Did you enjoy being in the limelight after all?
Brian Kobilka: Well, giving this presentation to the laureates made me nervous. And so many students. Students still make me nervous. I spent some time thinking what to say and how to say it without going over the time limit.
Nachrichten: Your lecture was on the prospects for drug development. What direction will your research take?
Kobilka: My lab is focusing on three areas. One is to go on looking at how receptors — and not only G protein-coupled receptors — engage signal proteins. There are other interesting proteins, too — kinases, for instance. Another area that I find very interesting is that these crystal structures are a kind of snap shot of how proteins work. So what we're doing is like trying to understand a complex activity from a series of still pictures. But we'd also like to be able to see how things work in real time — their dynamics. What we want is to see a single protein working in real time — to be able to watch conformational fluctuations. And to do these dynamics in a more physiological environment — maybe even in a real cell.
Nachrichten: And the third area?
Kobilka: Finding a way to apply the structural biology of G protein-coupled receptors to drug discovery. Obviously this has been done for many years with kinases and proteases. But we're not so good at getting robust crystals with GPCRs, G protein-coupled receptors. So when it comes to drug discovery, crystallography and structural biology will probably never be as versatile for membrane proteins. But I still think it's possible to try to take advantage of what we have learned from crystal structures and at least assist in drug discovery. Anything one can do will help.


<h2>How to get a Nobel prize</h2>
Nachrichten: Were you surprised to be awarded the Nobel Prize for chemistry and not for physiology or medicine?
Kobilka: I was plenty surprised just to get the Nobel Prize! It's being in chemistry does make sense, though physiology or medicine might have seemed more likely. As for me personally, I'm very proud to have received the prize in chemistry.
Nachrichten: You seem to have begun your research without thinking of GPCRs as a potential “hot topic”. Is that so?
Kobilka: Yes. I definitely did not care about “hot topics” or Nobel Prizes when I started my research. I just didn't know about all that, I come from a clinical background.
Nachrichten: So what do you make of this meeting here in Lindau as a signpost for the young to a Nobel Prize?
Kobilka: I do hope this is not the purpose of their or our being here. I mean, it's a fine opportunity for young people to meet with accomplished scientists and get excited about research and all. But I hope they're not set on getting a Nobel Prize. What I hope is that they want to do exciting science. Because that's what's important — not gearing their futures and careers toward a Nobel Prize. Young people should choose careers that excite them — careers where they can't wait to get to the lab every day and get to work. Then if they happen to get a Nobel prize for what they do, that's great. If they don't, but they're happy and are making contributions, that's great, too. That's what should motivate them.


<h2>Communication</h2>
Nachrichten: Tomorrow you will attend the podium discussion “Why communicate?”
Kobilka: Yes. I tried to get out of it, but I answered the e-mails too late. In fact, though, I do have some things to say about communication. You have to communicate with people from whom you can expect to get funding, but you also have to communicate with your fellow scientists, because it's your fellow scientists who judge your grants and decide whether you should get them or not. So, I think communication is very important. In fact, I often think more people hear about what we do by hearing our lectures than by reading our papers.
Nachrichten: I imagine that communication may be your main job now that you've received the Noble Prize.
Kobilka: The problem with the Nobel Prize is that you get asked to give a lot more talks and it's hard to say no. So in the next couple of months I'll have the challenge of figuring out how to do just that. I'm getting a lot more e-mail than I used to. This can be distracting, disruptive. So I figured out how to cut back on talks, and I really do. There are so many things that I want to do. I still like to do things with my own hands in the lab.


<h2>Rationalizing crystallization</h2>
Nachrichten: Is it true that you conducted the first experiments in crystallizing the beta-2 adrenergic receptor on your own because you didn't want to drag some unfortunate post-doc into this disaster field?
Kobilka: Yes, I did most of the work in crystallography between 1990 and the early 2000s, and I did much of it myself. It was just too risky for a post-doc or a PhD student. But in 2004 we got our first crystals. They weren't very nice crystals, but at least they were crystals. So then I felt we had entered the realm of the possible. In 2005 two really talented post-docs joined me in the lab, and they really made a difference. Having these young people to take on much of the work was critical.
Nachrichten: Do we have to start at “square 1” for every protein we want to crystallize or are we on the way to some rationalization?
Kobilka: We do have some general rules to follow. We know, for instance, that the protein has to have a certain level of stability, and we know that there can be a lot of unstructured bits on the surface. We know there has to be enough surface clarity for contact. So we can definitely do things to increase the probability of getting crystals. But there is still an element of luck. Sometimes, even, you make a protein one week and get crystals, and the next week you do exactly the same thing and don't get any. And you don't know why. You know you're lucky you got them the first time around, so at least you have some kind of a lead. So you sit down and do it again and again and in the end you do get them. At that point you try to refine them. At least I can say that we're better now at putting ourselves in a position to take advantage of the luck that comes our way.
Nachrichten: There is a lot of competition in some fields of chemistry. What's the situation in the GPCR community?
Kobilka: I would say it's always been pretty competitive. You know, even more people are getting involved these days, and this is good because it's doable now: we need more pictures of these proteins even if they're only snapshots. And there are different aspects of GPCR biology now. There are the structures. But there is a whole lot we still don't know. Going all the way from protein structure to cell physiology, to cell biology, to physiology and ultimately to drug discovery … I think the competition is good. In the GPCR field we try to help each other, for the most part, even if we compete we do it on friendly terms.


<h2>Nobelpreisträgertagungen in Lindau</h2>
Extreme Nobelpreisträgerdichten gibt es nicht nur in Harvard und Stanford, sondern auch jedes Jahr Anfang Juli auf der Insel Lindau im Bodensee. Die 63. Auflage des Lindau Nobel Laureate Meetings war der Chemie gewidmet und versammelte 34 Preisträger. Über 600 Nachwuchswissenschaftler aus 78 Ländern trafen dieses Jahr die Popstars der Wissenschaft und konnten sich inspirieren lassen.
Es ist nicht ganz einfach, zur Nobelpreisträgertagung geladen zu werden: Das Lindauer Kuratorium wählt nach einem mehrstufigen internationalen Bewerbungs- und Auswahlverfahren — in diesem Jahr waren über 150 akademische Partnerinstitutionen aus der ganzen Welt beteiligt — besonders qualifizierte Studierende, Doktoranden und Postdoktoranden aus. Denjenigen, die im Auswahlverfahren scheitern, bleibt nur noch der Weg, selbst den Nobelpreis zu gewinnen …
Die nächste Chemietagung in Lindau findet im Jahr 2017 statt. Bereits in zwei Jahren gibt es allerdings zur 65. Auflage ein interdisziplinäres Treffen, zu dem Nobelpreisträger aus Chemie, Physik und Medizin kommen werden.

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“Students still make me nervous”

2012 Nobel prize laureate Brian Kobilka about G protein-coupled receptors, communication and competition. Nachrichten aus der Chemie: Professor Kobilka, everyone agrees that you very much like to keep a low profile. Then yesterday you had to deliver the opening lecture here at the Lindau Nobel...

2011 Nobel prize laureate Dan Shechtman talks about quasicrystals, jewelry and being stubborn.


Nachrichten aus der Chemie: Professor Shechtman, this is not your first Nobel-Prize-Meeting now. You have already attended last year the Physics Meeting. But you are a Chemistry Nobel Prize Winner. Was this a surprise for you?
Dan Shechtman: That it was in Chemistry? Yes. And I shouldn't be surprised, and yet I was. Because all or most of the crystallography prizes I have received were in Chemistry, not in Physics. Someone told me, this year you are nominated again for the Nobel prize. And I assumed it was by physics. I was told that in the Nobel committees, they talk to each other and if I am nominated for Physics and for Chemistry, they make one file and they usually give it to Chemistry.
Nachrichten: In the mid-eighties, there were three ground-breaking discoveries concerning the chemistry of materials. The fullerenes, the high temperature super-conductors and your quasicrystals. The researchers of the two first ones received a Nobel Prize very fast. And you had to wait for 30 years. Did you believe finally, that you will ever get it?
Shechtman: I believe, I really think so, that anybody who gets the Nobel prize, deserves it. But that doesn't mean, when you deserve to get a Nobel prize, you will get it. It never bothered me, personally. I always said: They have better candidates than me. I was really cool about it and so it finally came as a total surprise. I was working on my computer, 11:15 in the morning. The phone rings: “Danny speaking”. “Hello, this is the Royal Swedish Academy of Sciences. Please hold the line. Very important message.” I said “Oh oh”. After the announcement they told me; don't tell anybody for half an hour, because at 11:45 we are going to announce it to the world. And so, I left my work, left the computer and was sitting there at my desk, just gazing at the floor in front of me, just looking, thinking, what's going to happen now? And I didn't even imagine, what actually happened after this. I thought: O.k. now there will be three or four more invitations from all over the world, I will speak here and there. I totally missed the reality.


<h2>Inspired to inspire</h2>
Nachrichten: In fact, it completely changed your life?
Shechtman: Yes. I travel around the world; I have endless number of invitations to many different places. I only accept a few, simply because unlike an electron I cannot be at two places at one time and so, but I really try … Let's put it this way: I'm inspired to inspire young people.
Nachrichten: I luckily attend your master class yesterday at the Lindau Nobel meeting. I had the impression that you enjoyed it to give your experience to the young people here.
Shechtman: Lindau is very special. There is no such meeting in the world, where so many Nobel Laureates meet so many students during the long time of one week, which is always full of interactions. This is really unique. Yes, I enjoy it. I am a teacher. I like people to understand what I am talking about. And this is why, I always start very simple. What is order? What is rotation symmetry? I want people to understand what I'm talking about. I feel like a missioner to pull on the education of the young generation. And with all this, promote peace in the world. We live in a very problematic world. We have to work hard, to calm it down and start working and do good things.
Nachrichten: You have always been a dedicated teacher: You have also invented a course at the Technion about entrepreneurship — it's called technological education?
Shechtman: Yes and I will be doing it now for 27 years. Year after year after year. By now I have about 10 000 graduates who are known engineers or scientists in Israel. So, over the last 25 years Israel become a start up nation and I'm proud I have contributed to this.


<h2>Jewelry — Handmade</h2>
Nachrichten: Your hobby is jewelry?
Shechtman: I have a basement with full equipment to do it. I can make jewelry like a little factory. I just don't have time. My last jewelry pieces were in the mid-nineties. All the jewelry belongs to my wife Zippi, a professor at the Haifa University. She gave it for a few months to the exhibition “A Jewel for my Wife” which is shown at Technion. But she always wears some of them.
Nachrichten: I see you are wearing a tie with a quasi-periodic array?
Shechtman: This tie was made for me by my University, the Technion, before my Nobel Prize for my Birthday. And after the Nobel prize the demand became so high, the Technion made 5000 more and now they probably will invest in the third series because they are running out of them.
Nachrichten: What was your way into science?
Shechtman: It was all accidental. I can tell you, when I was young, I wanted to become an engineer, because I admire this book called “The Mystery Island” by Jules Verne. And I can tell you a secret that I have this book with me now and I read it again now after 50 years that I haven't touched it. I brought it here with me, to recall. In this book, there are five characters, who are stranded on an island and they make everything that is necessary to survive — the leader there is a man who is an engineer. And they all obey him, and they all admire him and because he can do anything. And I wanted to be like him. And indeed, after my military service, I went to Technion, and studied mechanical engineering. But then, the year was 1966, it was a big recession in Israel and I couldn't find a job. So I said to myself, I will do my Master's degree and in two years I will find a job. But during these two years, I fell in love with science. And decided to go for my Ph.D. This is why I am here now.


<h2>Living as a maverick</h2>
Nachrichten: In the beginning it was very hard for you to convince people of quasicrystals. Was there one moment, when you wanted to go your lab-boss and say: Yeah, you are right, the crystalls are twins. There are no quasicrystals.
Shechtman: Never. You don't know me. I am almost never affected by other opinions. I repeated my experiments, I was an expert of electron microscopy, and I knew that my experiments were correct. And I said to the others: If you are trying to proof me wrong, repeat my experiments. Show me what is wrong in my experiments. Don't tell me this cannot be, just because you look in the books. And anybody, who repeated my experiments, said, Danny, fantastic. And all these people, who were against me — Linus Pauling as spearhead — were simply wrong. It is a pity: Pauling was really the greatest chemist of the 20th century, definitely in the United States. He was a great scientist. He fought me for ten years: 1984 — 1994 until he died. And he made fun of himself, because after a few years everybody knew that he was wrong. His Papers were finally rejected by the journals and went back to him and he really disgraced himself. It was a sad story.
Nachrichten: Why have quasicrystals not been discovered before 1982?
Shechtman: This is a very good question. Is it because they are very rare? No, there are hundreds of them. Is it because they're esoteric materials? No, they are made of iron and copper and aluminium and magnesium, we use millions of tons of this material around the world every year. Is it because they are not stable? Many are not stable, but what does it mean not stable? It means, that if you heat them up to 400 °C they will transform into something which is periodic. But at room temperature, they are stable.
Nachrichten: So what was the reason?
Shechtman: Electron Microscopy. Quasicrystals had to be discovered by electron microscopy, because they are very small. The traditional crystallographers wanted to have x-ray diffraction data. It took us three years to grow quasicrystals which were large enough. Once we had them — I didn't do that, friends of mine in France and Japan did it, the battle was won.
Nachrichten: But the initial discovery was only possible with electron microscopy?
Shechtman: Yes. And you not only had to be an electron microscopist, you had to be an expert of electron microscopy. And this is what I'm telling now to the students. Do you want to succeed in science or finish it? When you want to succeed in science, you must have a broad knowledge, but you have to develop one peak of expertise. Find something interesting. Bite it. Bite it like a Rottweiler dog. Don't let go. Don't let go until you know what it is. Listen to other people, but if they talk nonsense, shut them up. You have to be stubborn, not in a negative but in a positive sense.
Interview: Christian Remenyi, Vera Köster (<ext-link ext-link-type="uri"><a href="https://www.chemistryviews.org" target="_blank">www.chemistryviews.org</a></ext-link>)

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“Students still make me nervous”

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