Michael Levitt: a Pioneer of Computational Biology

Chemical reactions happen unbelievably fast. In fractions of a millisecond, electrons jump from one atom to another. Classical chemistry cannot keep up with this: neither can every step of a reaction be unveiled experimentally, nor can calculations based on classical physics simulate these fast and complex processes. Due to the pioneering research of Michael Levitt, together with Arieh Warshel and their Harvard colleague Martin Karplus, it’s now possible to have the classical Newtonian physics work side-by-side with simulations based on quantum physics.

Previously chemists had to choose. If they used classical physics, their calculations were simple and they could model large molecules. The downside was: chemical reactions couldn’t be simulated, especially not in the 1970s when this ground-breaking research was conducted. To simulate these reactions, chemists had to use models from quantum physics, meaning that every electron, every atomic nucleus etc. was accounted for. But these calculations require enormous computing power, meaning that their application was limited to really small molecules.

Nowadays, chemists apply the demanding quantum physics calculations only where they are needed: at the core of the reaction, also called the reaction centre. The rest of the molecule in question is modelled using classical physics. Taking into account that computers were infinitely slower in the early 1970s compared to computer speed today, Levitt and Warshel reduced the calculations even further: they merged several atoms in their model. In his autobiography on Nobelprize.org, Levitt comments: “How we dared to leave out 90 percent of the atoms is an interesting story.” Obviously, they reached “the right level of simplicity” with this approach: neither too complicated, nor so simple that the model would be meaningless.

But how did a shy young boy from South Africa become a world-class biophysicist? Of course, most of his success is due to his great intellectual talent. But his fierce perseverance also helped, as did many lucky coincidences. Let me give you three examples of the latter.

 

Michael Levitt during his talk at the Inscription Ceremony in the park surrounding the Museum of Natural History in New York City, when his name was added to the stone pillar where all names of American Nobel Laureates are inscribed. Photo: Consulate General of Sweden in New York City,2014, CC BY-SA 2.0

Michael Levitt during his talk at the Inscription Ceremony in the park surrounding the Museum of Natural History in New York City, when his name was added to the stone pillar where all the names of American Nobel Laureates are inscribed. Photo: Consulate General of Sweden in New York City, 2014, CC BY-SA 2.0

 

First of all, he had an aunt and uncle in London who were both established scientists: His aunt Tikvah Alper found that the infectious agent in Scrapie, a degenerative sheep and goat disease, did not contain nucleic acid. This finding was important in understanding the mechanisms of all forms of transmissible spongiform encephalopathy, like Creutzfeldt-Jakob disease in humans. Max Sterne, her husband and Levitt’s uncle, developed an effective and safe vaccine against anthrax in South Africa that is still used today. When young Michael Levitt visited them in London in late in 1963, he couldn’t help but become interested in life science. He later became one of the pioneers of computational biology; he first learned how to programme in Fortran during an internship in Berkeley that his aunt had organised for him a few years later.

In 1963, Michael Levitt was only sixteen and had already studied several months at Pretoria University. He spent the first few months in London “glued to [his] uncle and aunt’s TV set watching the Winter Olympics,” because he had never seen snow, and there had been no television in South Africa. But the BBC series “The Thread of Life” by Nobel Laureate John Kendrew, who had been awarded the Nobel Prize in Chemistry only one year earlier, made an even larger impression. For young Levitt, this was “a remarkable introduction to molecular biology”, because it had become clear just a few years earlier “that life was highly structured in space and time, just like a clock, but a billion times smaller and infinitely more complicated.” Already at this young age, he became fascinated by the role modern physics could play to elucidate biological processes.

In order to be admitted to a good British university, he had to pass A-level exams, his South African matriculation exam wasn’t sufficient. He chose to study at King’s College in London, where the tradition of biophysics was strong. After his first degree, he wanted to pursue a PhD at the Laboratory of Molecular Biology (LMB) in Cambridge. So he wrote to John Kendrew – only to get rejected. Michael Levitt persisted, asking to join LMB a year later, again without a clear result. But Levitt didn’t give up, put on his Bar Mitzvah suit and waited outside the offices of John Kendrew and Max Perutz, also a Nobel Laureate of 1962. The latter came out first, talked to Levitt and promised to consider his request. Finally, he was accepted as a doctoral student for one year later. But instead of the world trip that Levitt had imagined, he was sent to the Weizmann Institute in Israel to learn more about the force field method from Shneior Lifson, an important theory behind the computer modelling of large molecules, not to be confused with the force field in classical physics.

 

Michael Levitt photographed by Peter Badge. The transition from normal mortal to Nobel Laureate according to Levitt:

The transition from “being a mere mortal to a Nobel Prize winner” has many aspects, according to Levitt, including the following: “It is not easy when people start listening to all the nonsense you talk.” Photo: Peter Badge/Lindau Nobel Laureate Meetings

 

Being sent to Israel, after persevering in Cambridge, was the second lucky coincidence. As Levitt himself writes, his first year in Israel was “the real watershed” of his life: in only ten months, he laid the foundations both for a successful career in science and for a happy family life. Together with Arieh Warshel, another student and later co-recipient of the 2013 Nobel Prize, he wrote the computer programme that used the force field method to calculate properties of molecules. And Michael Levitt met his wife Rina only weeks after arriving in Israel, and they got married before he left again for Cambridge in August 1968 to finally pursue his PhD. A biologist by training, Rina Levitt later became an accomplished multimedia artist.

The third lucky coincidence happened in the mid-1980s, many years, numerous ground-breaking findings and publications later (and after moving back to Israel, then back to Cambridge, etc.): Rina and Michael Levitt where attending a private cocktail party in Cambridge, Massachusetts, when Nobel Laureate Roger Kornberg called and heard that they considered leaving Israel. Kornberg immediately suggested that Michael should come to Stanford – where he has been since 1987, and still is. “My dominant memory of coming to Stanford was how easy everything was. It seemed as if we had grown up on Jupiter and then moved to the Earth’s gravity.” Levitt founded his first research group and his first company, his eldest son attended Berkeley. A few years later, his wife and sons moved back to Israel so that all three boys could complete their military service. Levitt himself was “mainly in the air between Israel and Stanford” during this time. His wife moved back to Stanford, but a few years later left for Israel again to spend more time with their first grandchild.

“Just when I thought things could not get any better, I was woken at 2:16 AM on the morning of 9 October, 2013,” he remembers. Levitt had said to himself many times that “No one should expect the Nobel Prize,” so the call from Stockholm came as a great surprise.

We sincerely hope that Michael Levitt will be able to attend a Lindau Nobel Laureate Meeting in the coming years.

 

New Super Tool for Cell Biology

Researchers from Stefan Hell’s department at the Max Planck Institute for Biophysical Chemistry in Göttingen have achieved yet another breakthrough in light microscopy: With their new MINFLUX microscope they can separate molecules that are only a few nanometres apart, meaning its resolution is 100 times higher than conventional light microscopy, and about 20 times higher than super-resolution light microscopy.

The 2014 Nobel Prize in Chemistry was dedicated to the breaking of the optical diffraction limit. For more than a century, half the wavelength of light – about 200 nanometres – was considered the absolute limit for light microscopes. When Stefan Hell was studying physics in Heidelberg, this limit was still taught – but Hell couldn’t accept it. By developing stimulated emission depletion (STED) microscopy the following years, he was the first researcher to successfully venture beyond this limit in the 1990s, both theoretically and experimentally. Based on these breakthroughs he received the 2014 Nobel Prize in Chemistry, together with the American physicists Eric Betzig and William E. Moerner, “for the development of super-resolved fluorescence microscopy”.

But how does STED work, and how does it lay the foundations for MINFLUX? Hell explains STED in his own words: “If I cannot resolve two points because they are too close together and they are both emitting fluorescence, I need to darken one of them – and suddenly, you’re able to see the other point. If I make sure that all molecules are dark, except the one or the few that I’m interested in, then I can finally resolve this one, or these few.” The darkening is achieved by optical interference: Since a laser beam is used to excite fluorescence in molecules, it’s also possible to darken some molecules in the probe with a second laser beam whose wave properties cancel out the first beam. This second laser beam is doughnut-shaped, leaving only a small centre spot still emitting fluorescence. Thus STED functions by depleting a circular region of the sample, while leaving a small focal point (see graph below).

 

How a STED microscope works: with a laser excitation focus (left), a doughnut-shaped de-excitation focus (centre) and remaining fluorescence (right). Credit: Marcel Lauterbach, CC BY-SA 3.0

How a STED microscope works: with a laser excitation focus (left), a doughnut-shaped de-excitation focus (centre) and remaining fluorescence (right). Credit: Marcel Lauterbach, CC BY-SA 3.0

With the MINFLUX microscope, Hell’s research group combined the advantages of STED microscopy with the principles of PALM (photo-activated localization microscopy) developed by Eric Betzig. In PALM, also called PALM/STORM, single molecules are also excited by switching them on and off, but these molecules light up randomly, they’re not targeted. Betzig and his colleagues would use a very short laser pulse, thus exciting only a few molecules which could then be localised. As these molecules bleach out, the researchers turn the laser on again to see the next batch and so forth. Finally, the entire probe has been activated, seen and plotted. The result is a graphic resolution far beyond the diffraction limit.

With this approach, PALM already operates on the single-molecule level but the exact location of each molecules isn’t easily determined. With STED, the location of an excited molecule is well known, but the laser beam isn’t able to confine its emission to a single molecule. MINFLUX, on the other hand, switches individual molecules randomly on and off. Simultaneously, their exact positions are determined with a doughnut-shaped laser beam, something we know from STED. But in contrast to STED, this doughnut beam excites the fluorescence instead of darkening it. So if a molecule is located on the ring, it will glow; if it is exactly at the dark centre, it will not glow – but its exact position will be known.

Dr. Francisco Balzarotti, a researcher in Hell’s department, developed an algorithm to locate this centre position fast and with high precision. “With this algorithm, it was possible to exploit the potential of the doughnut excitation beam,” the first lead author of the Science paper explains. Klaus Gwosch, a PhD student in Hell’s group and third lead author, obtained the molecular-resolution images: “It was an incredible feeling as we, for the first time, were able to distinguish details with MINFLUX on the scale of a few nanometres”, the young physicist describes the team’s reaction to the potential of studying life at the molecular level.

 

Stefan Hell gemeinsam mit den Erstautoren der Studie Dr. Francisco Balzarotti, Yvan Eilers und Klaus Gwosch am Mikroskop (von links). Foto: Irene Böttcher-Gajewski, Max-Planck-Institut für biophysikalische Chemie

Stefan Hell and the three lead authors of the MINFLUX Science publication, Dr. Francisco Balzarotti, Yvan Eilers and Klaus Gwosch (from left) with their ground-breaking microscope. Photo: Irene Böttcher-Gajewski, Max Planck Institute for Biophysical Chemistry

In addition to the high optical resolution, this new microscope has another advantage over both STED and PALM: high temporal resolution. Stefan Hell: “MINFLUX is much faster in comparison. Since it works with a doughnut laser beam, it requires much lower light signal, i.e. fewer fluorescence photons, per molecule as compared to PALM/STORM for attaining the ultimate resolution.” MINFLUX stands for “MINimal emission FLUXes”, alluding to this reduced light requirement. Already with STED, researchers had been able to record real-time videos from the inside of living cells. But now it is possible to trace the movement of molecules in a cell with a 100 times better temporal resolution.

Yvan Eilers, another PhD student involved and the second lead author of the Science paper, was responsible for ‘filming’ protein actitivity within a living cell. He filmed the movements of ribosome subunits inside a living E. coli bacterium. “The past has shown that major resolution enhancements have led to new insights into the biology of cells, as STED and PALM have demonstrated,” Eilers elaborates. “Now everybody here is optimistic that this will hold true for MINFLUX as well.” The researchers in Hell’s group are convinced that in the future, even extremely fast changes in living cells will be investigated with the help of their new microscope, for instance the folding of proteins.

I asked Klaus Gwosch whether other research groups had already been in touch to acquire a MINFLUX microscope. “The Science publication has of course reached a large international audience,” he replied. “Currently, the department of NanoBiophotonics in Göttingen has the only MINFLUX microscope, but we expect other research groups to adopt and implement our approach.” His boss Stefan Hell agrees: “I am convinced that MINFLUX microscopes have the potential to become one of the most fundamental tools of cell biology. This could revolutionise our knowledge of the molecular processes occurring in living cells.”

Both Yvan Eilers and Klaus Gwosch will participate in the 67th Lindau Nobel Laureate Meeting this summer as young scientists, together with their doctoral adviser Stefan Hell. William Moerner, the third recipient of the 2014 Nobel Prize in Chemistry, will also attend and talk about super-resolution microscopy. We are looking forward to an interesting and inspiring week in Lindau!

 

 

MINFLUX microscopy separates molecules optically that are only a few nanometers apart. On the left, a schematic graph of the fluorescent molecules. PALM microscopy (right) only delivers a diffuse image of the molecules, whereas the position of each molecules can easily be discerned with MINFLUX (centre). Image: Klaus Gwosch, Max Planck Institute for Biophysical Chemistry

MINFLUX microscopy optically separates molecules that are only a few nanometers apart. A schematic graph of the target molecules is shown on the left. PALM microscopy (right) only delivers a diffuse image of these molecules, whereas the position of each molecule can easily be discerned with MINFLUX (centre). Image: Klaus Gwosch, Max Planck Institute for Biophysical Chemistry

Revealing the Secrets of Membrane Proteins

2.3 billion years ago, “the probably most significant extinction event in history” took place. This is how Hartmut Michel starts his 2015 lecture in Lindau, describing the Great Oxygenation Event, or GOE. What happened so early in the history of life? Ancestors of today’s cyanobacteria developed photosynthesis, a process that uses energy from sunlight, water and carbon dioxide to produce carbohydrates. Today, photosynthesis is considered “the most important chemical reaction on earth”, providing food for humans and animals, releasing oxygen for them to breathe – and millions of years later, this process provides fossil fuel in the form of oil, coal and natural gas, as Michel likes to point out.

But for the earliest single-cell organisms billions of years ago, free oxygen was a toxin. If they couldn’t somehow deal with large amounts of it in the atmosphere, as well as with the subsequent molecules from the ‘reactive oxygen species’ ROS, they died. One very effective way to ‘deal’ with free oxygen is the production of ‘oxygen reductases’: proteins that reduce oxygen to water, and simultaneously conserve the energy inherent in this chemical reaction. For more than the last ten years, Hartmut Michel has studied different oxygen reductases at the Max Planck Institute of Biophysics in Frankfurt, where he became director in 1987. One year later, Hartmut Michel was awarded the 1988 Nobel Prize in Chemistry “for the determination of the three-dimensional structure of a photosynthetic reaction centre”, together with Johann Deisenhofer and Robert Huber. More about photosynthesis in a minute.

 

The electron transport chain in the mitonchondrial intermembrane space. Cytochrome c is part of Complex IV. Graph: T-Fork, based on graph by LadyofHats, both public domain

The electron transport chain in the mitonchondrial intermembrane space. Cytochrome c oxidase is part of Complex IV. Graph: T-Fork, based on graph by LadyofHats, both public domain

 

In recent years, Michel and his research group mainly studied two types of oxygen reductases: the so-called superfamily of ‘heme-copper oxidases’, and the ‘cytochrome bd oxidase’. All of these oxidases are located in membranes and are thus called ‘membrane integrated terminal oxidases’. A famous example from the superfamily is cytochrome c oxidase, the last enzyme in the respiratory electron transport chain located in the mitochondrial membrane (see graph). It receives one electron from each of four cytochrome c molecules, transfers them to an oxygen molecule, converting molecular oxygen to two molecules of water. It also helps to pump the protons, which the ATP synthase needs to make ATP, across the membrane: “the general energy currency of life”, as Michel explained in his 2015 Lindau lecture. Did you know that your body produces an astounding amount of 70 kg of ATP every day to provide ‘fuel’ for its many processes? These include breathing, digesting and maintaining body heat, etc.

 

Hartmut Michel during his 2014 lecture at the 64th Lindau Nobel Laureate Meeting. Photo: Christian Flemming/LNLM

Hartmut Michel during his 2014 lecture at the 64th Lindau Nobel Laureate Meeting. Photo: Christian Flemming/LNLM

Interestingly, many oxygen reductases seem to have developed before the GOE. If this holds true – what were their functions? This is a ‘paradox’ that researchers haven’t solved yet. Another astounding result of Michel’s research is the fact that the two forms of oxygen reductases that he studies have many similarities, despite their structural differences: for instance, they both transport four electrons simultaneously, thus preventing the formation of ROS. “So obviously, the same mechanism was invented twice by Mother Nature,” Michel concludes in his lecture.

The photosynthetic reaction center is a membrane protein as well – the very first membrane protein whose structure could be elucidated. When Michel studied biochemistry in Tübingen and Würzburg, textbooks stated as an irrevocable fact that membrane proteins could not be crystallized. Since x-ray crystallography was, and still is, the best way to reveal the molecular structure of proteins, neither their structure nor their function could be determined without crystallization. Incidentally, many Nobel prizes were awarded in the last 100 years for developing x-ray crystallography.

But Hartmut Michel didn’t accept this scientific consensus. One major obstacle in crystallizing membrane proteins was that they are actually membrane proteins and lipids together, meaning the membrane is partly hydrophobic and it is thus impossible to create an aqueous solution. To solve this problem, detergents were needed, but they tend to form large micelles that can obscure the protein within. Finally, Michel found a fitting detergent, Heptan-1,2,3-triol, that forms smaller molecule clusters. Now, he had to decide on a membrane protein: He finally chose to work with the purple bacterium Rhodopseudomonas viridis, the name meaning “a red pseudo cell that is green”. These bacteria are capable of photosynthesis, like many plants, and their reaction centre could be isolated.

 

Determining protein structures with the help of x-ray crystallization is a very elaborate process: first, the protein needs to be crystallized, and this is very difficult with membrane proteins. Next, x-rays reveal a refraction pattern that's transformed into an electron density map with the help of advanced calculus. Finally, the protein structure is derived from this. Graph: Thomas Splettstoesser, www.scistyle.com, CC BY-SA 3.0

Determining protein structures with the help of x-ray crystallography is a very elaborate process: first, the protein needs to be crystallized, and this is very difficult with membrane proteins. Next, x-rays reveal a diffraction pattern that’s transformed into an electron density map with the help of advanced calculus. Finally, the protein structure is derived from this, again with advanced mathematics. Graph: Thomas Splettstoesser, www.scistyle.com, CC BY-SA 3.0

Johann Deisenhofer and Robert Huber provided the mathematics required for the elucidation of their atomic structure. The researchers first published their results in 1985, and received the Nobel Prize in Chemistry for this finding only three years later. In the early 1980s, it took Michel about four months to create an entire data set (see graph on right). Nowadays, one set can be created within seconds. Since their first publication, the atomic structures of more than 600 membrane proteins have been identified. Only about 50 of these are human membrane proteins – but there are several thousands in total! So there’s still a lot to be done.

Why is it so important to understand more about human membrane proteins? 80 percent of all current drugs affect membrane proteins, and more than 50 percent of all drugs target them directly. These proteins play a crucial role in infections, both viral and bacterial, as well as in many forms of cancer. That’s why Hartmut Michel concluded his 2016 Lindau lecture: “Most diseases are caused by a malfunction, understimulation or overstimulation of a certain membrane protein.” Consequently, understanding human membrane proteins could dramatically help cure disease.

Hartmut Michel is a committed supporter of the Lindau Nobel Laureate Meetings: he visited them twenty times, seven videos of his lectures are available here, and he’s also a member of the meetings’ Council. We’re looking forward to welcoming him in June 2017 at the 67th Meeting dedicated to chemistry.

 

 

 

 

Membranproteinen ihre Geheimnisse entlocken

Vor ungefähr 2,3 Milliarden Jahren kam es „zum wohl größten Massensterben der Erdgeschichte“, so Hartmut Michel zu Beginn seines Vortrags auf der Lindauer Nobelpreisträgertagung 2015. Er beschreibt die sogenannte Große Sauerstoffkatastrophe (englisch GOE, für Great Oxygenation Event), die sich ereignete, als erstmals große Mengen an freiem Sauerstoff in die Atmosphäre gelangten – für die Mehrzahl der damals existierenden Organismen ein tödliches Gift. Doch wie kam es dazu? Die Vorfahren der heutigen Cyanobakterien entwickelten die Photosynthese: Mit Hilfe von Licht, Wasser und Kohlendioxid stellten sie Sauerstoff und Kohlenhydrate in bislang nie dagewesenen Mengen her.

Hartmut Michel erhielt den Chemienobelpreis 1988 „für die Ermittlung der dreidimensionalen Struktur eines Photosynthesezentrums“, zusammen mit Johann Deisenhofer und Robert Huber. Das Nobelpreiskomitee nannte die Photosynthese „die wichigste chemische Reaktion auf Erden“, weil sie Atemluft und Nahrung für Mensch und Tier bereitstellt. Zudem ist sie für die Entstehung der meisten fossilen Energiequellen wie Kohle, Öl und Gas verantwortlich, allerdings mit ein paar Millionen Jahren Verzögerung.

Vor Milliarden Jahren standen die Kleinstlebewesen vor der Herausforderung, mit den großen Sauerstoffmengen zurechtzukommen. Außerdem mussten sie mit den Molekülen der sogenannten reaktive Sauerstoffspezies umgehen können (englisch ROS, für reactive oxygen species). Ein sehr effizienter Weg, freien Sauerstoff unschädlich zu machen, sind Sauerstoff-Reduktasen, also spezielle Enzyme, die Sauerstoff zu Wasser reduzieren. Sie werden auch Oxidoreduktasen genannt. Gleichzeitig helfen sie, die Energie zu speichern, die bei solchen Reaktionen freigesetzt wird. Seit über zehn Jahren analysiert Hartmut Michel nun solche Reduktasen am Max-Planck-Institut für Biophysik in Frankfurt am Main, wo er seit 1987 Direktor ist.

 

Schematische Darstellung des Elektronentransport der inneren Mitochondrienmembran. Die Cytochrom-c-Oxidase ist Teil des Komplex IV. Grafik: T-Fork, auf der basis der Grafik von LadyofHats, beide public domain

Schematische Darstellung des Elektronentransports in der inneren Mitochondrienmembran. Die Cytochrom-c-Oxidase ist Teil von Komplex IV. Grafik: T-Fork, auf der basis der Grafik von LadyofHats, beide public domain

 

In den vergangenen Jahren analysierte Hartmut Michel zusammen mit seiner Forschungsgruppe vor allem zwei Sorten von Oxidoreduktasen: Die Superfamilie der Häm-Kupfer-Oxidasen und die Cytochrom-bd-Oxidase. All diese Oxidasen befinden sich in Membranen. Ein bekanntes Beispiel der Superfamilie ist die Cytochrom-c-Oxidase, das letzte Enzym im Elektronentransport der inneren Mitochondrienmembran (siehe Grafik oben). Diese Oxidase erhält jeweils ein Elektron von vier Cytochrom-c-Molekülen und transportiert diese zu Sauerstoffmolekülen. Aus diesen Zutaten werden zwei Wassermoleküle gebildet. Sie ist außerdem behilflich, zwei Protonen, die für die Bildung von ATP nötig sind, durch die Membran hindurch zu pumpen. „ATP ist die allgemeine Energiewährung des Lebens“, erklärt Michel in seinem Lindau-Vortrag von 2015. Wussten Sie, dass Ihr Körper täglich bis zu 75 kg ATP produziert, damit wir zum Atmen, Verdauen und Bewegen ausreichend Energie zur Verfügung haben? Außerdem müssen wir unsere Körpertemperatur halten, und es gibt viele weitere Prozesse im Körper, die viel Energie benötigen.

 

Hartmut Michel während seines Vortrags in Lindau beim 64. Nobelpreisträgertreffen 2014. Foto: Christian Flemming/Lindau Nobel Laureate Meeting

Hartmut Michel während seines Vortrags in Lindau bei der 64. Nobelpreisträgertagung 2014. Foto: Christian Flemming/Lindau Nobel Laureate Meetings

Interessanterweise waren Oxidoreduktasen wohl bereits vorhanden, bevor sich freier Sauerstoff massenhaft in der Atmosphäre anreicherte. Aber welche Funktion hatten sie damals? Dieses ‘Paradox’ hat die Forschung bislang nicht aufklären können. Ein weiteres interessantes Ergebnis von Michel ist, dass sich die beiden Oxidase-Gruppen zwar strukturell deutlich unterscheiden, aber doch etliche Gemeinsamkeiten aufweisen: Beispielsweise transportieren beide Systeme häufig vier Elektronen gleichzeitig – so wird die Bildung von ROS effektiv verhindert. „Es scheint, als habe Mutter Natur dieselbe Erfindung gleich zweimal gemacht“, folgert Michel in seinem Vortrag.

Das photosynthetische Reaktionszentrum, für dessen Beschreibung Michel, Deisenhofer und Huber den Nobelpreis erhielten, ist ebenfalls ein Membranprotein – das allererste, dessen Struktur bestimmt werden konnte. Als Hartmut Michel noch Student in Tübingen und Würzburg war, galt die Lehrmeinung, dass Membranproteine grundsätzlich nicht kristallisiert werden können. Damals wie heute ist die Röntgenstrukturanalyse die beste Methode, um die molekulare Struktur, und damit die Funktion von Proteinen, zu ermitteln. Ohne Kristallisation kann sie jedoch nicht angewendet werden. Für die Entwicklung und Verbesserung der Röntgenstrukturanalyse wurden in den letzten hundert Jahren übrigens etliche Nobelpreise verliehen.

Doch Hartmut Michel wollte sich nicht mit der herrschenden Lehrmeinung abfinden. Also machte er sich daran, das erste Membranprotein zu kristallisieren. Ein großes Problem hierbei war die Tatsache, dass es sich bei diesen Proteinen eigentlich um eine Mischung aus Lipiden und Proteinen handelt, was dazu führt, dass sie teilweise hydrophob sind, also wasserabweisend, und sie deshalb nicht in wässrigen Flüssigkeiten gelöst werden können. Also braucht man Lösungsmittel, und Michel machte sich auf die Suche nach passenden sogenannten Detergenzien. Viele von ihnen bilden jedoch Mizellen. Das sind Zusammenballungen von Seifenmolekülen, die ihre hydrophilen Enden nach außen und die hydrophoben nach innen ausrichten. Der Nachteil hierbei ist, dass die gelösten Proteine in den dichten Mizellen ‘versteckt’ werden können.

 

Die Struktur eines Proteins mit Hilfe der Röntgenstrukturanalyse zu ermitteln ist ein aufwändiges Verfahren: Zunächst einmal muss das Protein kristallisiert werden, das ist bei Membranproteinen besonders schwierig. Dann wird mit Röntgenstrahlen ein Beugungsbild erstellt (diffraction pattern). Mit fortgeschrittener Analysis wird aus diesem Bild eine Elektronendichtekarte ermittelt, schließlich kann auch eine Struktur des Moleküls errechnet werden. Grafik: Thomas Splettstoesser, www.scistyle.com, CC BY-SA 3.0

Die Röntgenstrukturanalyse ist ein aufwändiges Verfahren: Zunächst einmal muss das Protein kristallisiert werden. Das ist bei Membranproteinen besonders schwierig. Dann wird mit Röntgenstrahlen ein Beugungsbild erstellt (diffraction pattern). Mit fortgeschrittener Analysis wird aus diesem Bild eine Elektronendichtekarte ermittelt. Schließlich kann auch die Struktur des Moleküls errechnet werden. Grafik: Thomas Splettstoesser, www.scistyle.com, CC BY-SA 3.0

Endlich fand Michel ein passendes Lösungsmittel, Heptan-1,2,3-triol, das kleinere Molekül-Verklumpungen bildet, sodass die Proteine herausgelöst, kristallisiert und analysiert werden können. Als nächstes musste er sich für ein bestimmtes Membranprotein entscheiden. Nach mehreren Fehlversuchen entschied er sich für das Purpurbakterium Rhodopseudomonas viridis, wörtlich „eine rote, falsche Zelle, die grün ist“. Diese Bakterien sind Photosynthese-fähig, genau wie Pflanzen, und ihr Reaktionszentrum hierfür kann isoliert werden. Auf diese Weise gelang Michel 1981 die Kristallisation des ersten Membranproteins.

Doch mit der Kristallisation war es nicht getan: Die Röntgenstrukturanalyse erfordert eine anspruchsvolle höhere Mathematik, um aus dem Beugungsbild der Röntgenstrahlen an den Elektronen des Kristalls eine dreidimensionale Struktur zu errechnen (siehe Schaubild rechts). Der Beitrag von Deisenhofer und Huber an diesem Projekt waren diese mathematischen Methoden. Die drei Forscher publizierten ihre Ergebnisse 1985. Nur drei Jahre später erhielten sie dafür den Chemienobelpreis. In den frühen 1980er Jahren brauchte Hartmut Michel noch ungefähr vier Monate, um einen kompletten Datensatz mit vielen Röntgenbildern zu erstellen. Heute entsteht ein solcher Datensatz automatisch innerhalb von Sekunden.

Seit dieser ersten Entdeckung entschlüsselten Forscher die Strukturen von über 600 Membranproteinen. Ungefähr fünfzig davon sind menschliche Membranproteine – doch es gibt insgesamt mehrere tausend! Hier ist also noch eine Menge zu tun.
Warum ist es überhaupt so wichtig, die Struktur und Funktion von diesen Proteinen zu kennen? 80 Prozent aller Arzneimittel wirken auf Membranproteine, und über 50 Prozent von ihnen haben diese Proteine als Zielstruktur. Das hat einen Grund: Sie spielen bei vielen Infektionen eine Schlüsselrolle, sowohl bei Viren als auch bei Bakterien, und sie sind an vielen Krebserkrankungen beteiligt. Diese Tatsache fasst Michel in seinem 2016er Lindau-Vortrag folgendermaßen zusammen: „Die meisten Krankheiten entstehen entweder durch eine Fehlfunktion, oder durch eine Über- oder Unterstimulierung eines bestimmten Membranproteins.“

Hartmut Michel ist ein langjähriger Unterstützer der Lindauer Nobelpreisträgertagungen. Er nahm bisher an zwanzig Tagungen teil, Videos seiner Vorträge finden Sie hier. Und er ist Mitglied im Kuratorium der Lindauer Nobelpreisträgertagungen. Wir freuen uns sehr, ihn im Juni 2017 bei der 67. Tagung, die dem Fach Chemie gewidmet ist, begrüßen zu dürfen.

 

 

 

Roger Tsien: “All Colours of the Rainbow”

Roger Tsien was one of the most productive and creative contemporary chemists. He’d been awarded the 2008 Nobel Prize in Chemistry “for the discovery and development of the green fluorescent protein, GFP”, together with Martin Chalfie and Osamu Shimomura. GFPs enable researchers to watch live cells at work: If they’re interested in a certain protein that can be expressed by an organism, they can fuse the GFP gene with the protein-encoding gene. From now on, each protein molecule can be traced through all its stages with the help of blue to ultraviolet light via fluorescence.

The advantage over many other markers is the fact that GFP is non-toxic, and also the light to see its fluorescence is non-toxic. GFPs have been widely used in many species, from yeast to insects, fish and mammals, as well as in human cells. The original GFP molecule was discovered in the jellyfish Aequorea victoria. This is why Roger Tsien thanked the jellyfish in his banquet speech at the official Nobel Prize Banquet Dinner on December 10th, 2008: “So my final thanks are to both the jellyfish and corals: long may they have intact habitats in which to shine!” Some of the fluorescent dyes developed by his research group were also derived from corals, others from bacteria.

 

With the help of genetic engineering, the GFP gene can be fused to target genes that will glow in ultraviolet light - also generations later! Slide from Roger Tsien's LNLM lecture in 2010. Photo: Bastian Greshake, CC BY-SA 2.0

With the help of genetic engineering, one of this mouse’s genes was fused with the GFP gene so that it glows under ultraviolet light. Also generations later, this mouse’s offspring will shine! Slide from Roger Tsien’s Lindau lecture in 2010. Photo: Bastian Greshake, CC BY-SA 2.0

 

Already as a PhD student of physiology in Cambridge, UK, Roger Tsien had developed his first tracking dyes for calcium activity in living cells. He hadn’t told his PhD supervisor about his new research adventure because he was sure that he would only explain how important it was to finish one project before starting a new one. Some of these dyes are still used today, like BAPTA and Fura-2; the latter was developed when Tsien had already become an assistant professor at the Department of Physiology-Anatomy at Berkeley.

After his move to UCSD in San Diego in 1989, mostly for better lab equipment, the Tsien group found fluorescent indicators that “glow in all colours of the rainbow”, as the Nobel Prize committee wrote. Over the years, his research group has also developed fluorescent indicators for ions like magnesium, copper, iron, lead, cadmium, and many more.

From an early age, Roger Tsien had been fascinated with the chemistry of colours. “I’ve always been attracted to colours,” he told the San Diego Union-Tribune when he learned that he had ben awarded the Nobel Prize. “If I had been born colour-blind, I probably never would have gone into this.” And in his autobiography for the website Nobelprize.org he wrote how his first chemical experiments in the basement of his parent’s house in Livingston, New Jersey, reflect “an early and long-lasting obsession with pretty colours”. He captions this essay with the following joke: “What do elementary school pupils and Nobel Laureates have in common? They both have to write autobiographical essays on command.”

 

 

Roger Tsien’s father was an aviation engineer with a degree from MIT, but couldn’t find a suitable job because as a Chinese, he didn’t get the necessary security clearance. After several different jobs, he found work in the vaccum tube division of RCA, Radio Corporation of America, in New Jersey. When his parents wanted to buy a house in New Jersey, the developer wouldn’t sell it to them because they were Chinese, fearing that other families wouldn’t buy property next to them. His parents wrote to the New Jersey governor to complain, and the governor in turn wrote to the developer that racial discrimination was illegal. Not only could the Tsien family then buy the house – years later, the same developer used Roger’s photo as the winner of the nationwide Westinghouse Science Talent Search to advertise how good the Livingston schools were.

Only sixteen years old, much younger than most other contestants, Roger Tsien had written up his results from an NSF-sponsored summer programme at Ohio University that he had attended in the summer of 1967, his “first exposure to a research environment”. He was assigned a project where he had to analyse how metals bind to thiocyanate. “For lack of any alternatives, I wrote up my Ohio University project, trying my best to draw some conclusions from a mess of dubious data.” To his own surprise, Roger Tsien won the first prize.

 

San Diego beach scene drawn with an eight colour palette of bacterial colonies expressing fluorescent proteins derived from GFP and the red-fluorescent coral protein. Artwork by Nathan Shaner, photography by Paul Steinbach, created in the lab of Roger Tsien in 2006. Credit: Nathan Shaner, CC BY-SA 3.0

San Diego beach scene drawn with an eight colour palette of bacterial colonies expressing fluorescent proteins derived from GFP and red-fluorescent coral protein. Artwork by Nathan Shaner, photo by Paul Steinbach, created in the lab of Roger Tsien in 2006. Credit: Nathan Shaner, CC BY-SA 3.0

The same year, he started college at Harvard University with a scholarship, where he earned a Bachelor of Science in chemistry and physics, followed by a PhD in physiology from the University of Cambridge – and a productive career in the lab discovering and applying fluorescent dyes. Roger Tsien came to five Lindau Meetings, and the five lectures he gave demonstrate his wide interest in many scientific topics. In his 2015 lecture for instance (see above video), he explains his recent interest in two seemingly very different research areas: cancer therapy and long-term memory storage. But interestingly, both topics touch upon the same enzymes called proteases: enzymes that can cut proteins. Tsien himself explains his motivation for cancer research with the fact that his father died of pancreatic cancer. Together with medical doctor Quyen T. Nguyen he developed ‘fluorescence-guided surgery’ that helps the surgeon not only to find most cancer cells around a tumour, but also to preserve as many nerves and other important structures as possible.

The second topic of his 2015 lecture concerns memory storage in the perineuronal net, or PNN, an extracellular matrix structure that stabilises the adult brain. After a lifetime of studying intracellular activities, “here I’m forced to learn about extracellular matrix!” Tsien said in 2015. ‘Holes’ in the PNN act as the storage medium, “like a 3D punch card”, he explains, only to realise that today’s young scientists have never handled a punch card. In a mouse model, he was able to delete many long-term memories with the help of a certain matrix metalloproteinase, or MMP. He expects an even larger deletion share if more enzymes involved are understood. Sounds like the ‘neuralyzer’ from the Men in Black movies that can delete memories, doesn’t it?

On August 24th, 2016 Roger Tsien died unexpectedly on a bike trail in Eugene, Oregon, aged only 64. On this day, the world lost a brilliant scientist as well as a wonderful person with a great sense of humour.

 

Roger Tsien with young scientists on the annual boat trip to Mainau island on the last day of the 2009 Lindau Nobel Laureate Meeting, dedicated to chemistry. Photo: Christian Flemming

Roger Tsien (1952 – 2016) with young scientists on the annual boat trip to Mainau island on the last day of the 2009 Lindau Nobel Laureate Meeting, dedicated to chemistry. Photo: Christian Flemming/Lindau Nobel Laureate Meetings

Committed to Teaching Science and Entrepreneurship: Dan Shechtman

On the beautiful Mainau garden island in Lake Constance where the Closing Panel Discussion of the 2016 Lindau Nobel Laureate Meeting took place, Dan Shechtman gave insights into his long and productive career. After finishing his degree in mechanical engineering at the Technion in Haifa, he couldn’t find a job due to the economic crisis of 1966. So he continued his studies and thought he would find a job after the recession. But then he “fell in love with science” and decided to continue for his PhD – and we know that this was a very wise choice.

But during his initial job hunt in the mid-sixties, the Technion, Israel’s prestigious Institute of Technology, didn’t encourage its students to start their own businesses. “The spirit of the Technion told us: you will be so good that when you graduate, everybody will want to hire you,” Shechtman recounts in the Mainau panel discussion. “And I said: ‘Oh, that is very wonderful, but what if I want to open my own technology business? How do I do that?'” The Technion didn’t teach that. So when he became a full professor at the very same Technion 1986, after his discoveries of quasicrystals that later won him the Nobel Prize, he told himself: “Now I can do whatever I want,” and he immediately started planning the course ‘Technological Entrepreneurship’, a term he invented. Only one year later, he offered his first course, it’s now in its 29th year. When Shechtman announced this course for the first time, 800 students came to attend, but the hall was only approved for 600 people – “the largest class of the Technion ever”, as he remembers.

 

Dan Shechtman's 2016 lecture in Lindau: The Science and Beauty of Soap Bubbles, view here. Photo: Rolf Schultes/Lindau Nobel Laureate Meetings

Dan Shechtman’s 2016 lecture in Lindau: ‘The Science and Beauty of Soap Bubbles’, view here. Photo: Rolf Schultes/Lindau Nobel Laureate Meetings

Today, Israel has more companies quoted on the American exchange platform NASDAQ than any other country outside the US except China, and most major high-tech companies have research and development departments in Israel. How come such a small country with only about 7 million inhabitants produces more start-up companies than large stable nations like Japan, India, Canada and the United Kingdom, asks the book ‘Start-Up Nation’. The authors see high levels of immigration and Israel’s mandatory military service as two contributing factors. When approached on this subject, Shechtman remarks: “I don’t claim that I’m the father of the start-up nation, but I contributed to it. (…) By now I have very many engineers and scientists in my country, more than 10,000, that took my class and had the chip of entrepreneurship embedded in their minds.”

To these classes he would invite three groups of speakers: successful entrepreneurs, struggling entrepreneurs, and professionals like lawyers, accountants, patent officers and marketing experts: the classic start-up advice. And although the word ‘start-up’ wasn’t used when his course started, ‘technological entrepreneurship’ was already tailored to the needs of future technology companies. Besides practical advice, the students also learn about failure. They would hear that out of ten newly established technology companies, one is a big success, two struggle, and seven will fail. And they learn that failure is Okay, that next time they’ll be much more successful. Some of Shechtman’s many lectures even have the title ‘Failure? OK, Start Again!’

In an interview with The Guardian, Dan Shechtman says how he feels “like a missionary to promote education and science and technological entrepreneurship.” So besides ‘real science’ and technological entrepreneurship, the Nobel laureate is passionate about science education because “every society needs more engineers and scientists, and biologists and computer experts. These are people that open start-ups and develop economies,” as he explains in the Mainau discussion. However, he sees a widespread phenomenon that “young people don’t want to become any of these, they want to be managers and lawyers and accountants,” which is fine in his opinion, but these professions don’t produce anything. “And start-up companies, high-tech companies, small companies that will grow – this will lead us to a better future,” meaning more prosperity for larger parts of the world population.

 

Shechtman’s opening statement at the panel discussion The Future of Education in Sciences was: “The most important resource of any country, and the most sustainable one, is human ingenuity. And we have to foster it, and we have to develop it as early as possible” – a strong sentence, and he acts upon it. In 2012, he initiated a programme in his hometown Haifa to educate kindergarten teachers in scientific topics. They in turn were expected to teach science to kindergarten children. But “part of it was lost in translation,” Shechtman says in hindsight. Some teachers couldn’t really understand what they were supposed to teach, so the teaching didn’t work very well.

Dan Shechtman drew two conclusions: he wanted to teach young children more directly, but he also wanted to reach a larger audience. So on the one hand, he helped a programme to install ‘Science Kindergartens’ in Israel: the first opened in October 2015. On the other hand, he contacted the national educational television channel and proposed a TV sience show for young children in order to reach a larger audience. The show is called ‘Being a Scientist with Prof. Dan’, in Hebrew this sentence rhymes.

The TV channel built a small laboratory in a TV studio, and Prof. Dan has a young actress as his assistant. For every 15-minute show, three children aged six are invited to discuss science topic with the adults: How are things measured? What is matter? How is matter built? How does light interact with matter? What are fields – gravitational fields and magnetic fields? You can watch these shows on youtube, but since they’re tagged in Hebrew letters, I recommend to use these links (show on matter, fields, atoms and crystals, and measuring). It’s a delight to see how passionately Prof. Dan and his assistant explain scientific topics, and how much fun the children have in taking part.

This year Dan Shechtman talked about ‘The Beauty and Science of Soap Bubbles’ in Lindau. This inspiring lecture is supposed to be the starting point for a series on ‘Science and Aesthetics’ that he’s planning. In 2017, he will give a Lindau lecture about crystallography – the topic for which he was awarded the Nobel Prize in Chemistry in 2011.

 

Dan Shechtman: Forscher als Unternehmer ausbilden

Die Abschluss-Podiumsdiskussion der Lindauer Nobelpreisträgertagung fand auch 2016 wieder auf der Bodenseeinsel Mainau statt. Dan Shechtman gehörte zu den Diskutanten über das Thema ‘Wissenschaftliche Ausbildung in der Zukunft’ und gewährte Einblicke in seine ereignisreiche Karriere und sein vielfältiges Engagement. Alles begann mit einem Studium des Maschinenbaus am Technion in Haifa. Doch nach seinem Bachelorabschluss fand er in der Wirtschaftskrise 1966 keinen Job. Also studierte er weiter in der Hoffnung, mit einem Mastersabschluss später eine Anstellung zu finden, doch er “verliebte sich in die Wissenschaft”, wie er dem britischen Guardian anvertraute und entschloss sich zu einer Promotion – eine weise Entscheidung, wie wir heute wissen.

Während seiner ersten, erfolglosen Jobsuche unterstützte das Technion ihn und andere Studenten nicht darin, sich selbstständig zu machen. “Die vorherrschende Haltung war: Wenn ihr hier euren Abschluss macht, werdet ihr so gut sein, dass sich die Arbeitgeber um euch reißen,” erinnert sich Shechtman heute. “Ich meinte damals nur: ‘Das ist ja alles schön und gut, aber was ist, wenn ich mein eigenes Unternehmen gründen möchte?'” Am Technion erhielt er keine zufriedenstellende Antwort auf diese Frage, dort gab es keine Kurse über Existenzgründung. Als er 1986 zum Professor am Technion berufen wurde, sagte er sich: “Jetzt kann ich endlich machen, was ich schon immer wollte.” Sofort begann er mit der Planung des Kurses ‘Technological Entrepreneurship’. 1987 fand der erste Kurs statt, er wird seit 29 Jahren kontinuierlich angeboten. Zur ersten Veranstaltung kamen 800 Studenten, der Saal war jedoch nur für 600 zugelassen: “Der größte Kurs, den es am Technion jemals gab,” erinnert sich Shechtman gerne.

 

Dan Shechtman während seines Lindau-Vortrags 2016: Über die Schönheit und Wissenschaft der Seifenblasen. Sehen Sie den ganzen Vortrag hier. Photo: Rolf Schultes/Lindau Nobel Laureate Meetings

Dan Shechtman während seines Lindau-Vortrags 2016: Über die Schönheit und Wissenschaft der Seifenblasen. Sehen Sie den ganzen Vortrag hier. Photo: Rolf Schultes/Lindau Nobel Laureate Meetings

Heute sind mehr israelische Firmen im amerikanischen Aktienbörse NASDAQ notiert als aus irgendeinem anderen Land außerhalb der USA, mit Ausnahme Chinas. Und die allermeisten Hightech-Konzerne betreiben Forschungsabteilungen in Israel. Wie kommt es, dass ein kleines Land mit nur rund sieben Millionen Einwohnern mehr Start-Up-Unternehmen hervorbringt als große Länder wie Japan, Kanada, Indien oder Großbritannien? Das Buch ‘Start-Up Nation’ widmet sich dieser Frage, die Autoren identifizieren einerseits die starke Zuwanderung nach Israel, andererseits die Wehrpflicht als zwei Säulen dieses Erfolgs. Wenn man Shechtman auf dieses Buch anspricht, antwortet er: “Ich nehme für mich nicht in Anspruch, der Vater der Start-Up-Nation zu sein, aber ich denke, dass ich meinen Teil dazu beigetragen habe. (…) Zurzeit arbeiten über 10.000 Forscher und Ingenieure in Israel, die meinen Kurs besucht haben – ihnen wurde sozusagen ein Chip fürs Unternehmertum eingepflanzt.”

Im Rahmen eines solchen Kurses lädt er drei verschiedene Arten von Rednern ein: erfolgreiche Unternehmer, Unternehmer mit Problemen, sowie Berater wie Anwälte, Buchhalter, Experten für Patentrecht, Marketingexperten etc., also Experten, die in jeder klassischen Exitenzgründungsberatung zu Wort kämen. Zwar war das Wort ‘Start-Up’ noch wenig gebräuchlich, als Shechtmans Kurs startete, trotzdem widmet sich diese Veranstaltung ganz den Bedürfnissen künftiger Tech-Unternehmern. In den Kursen geht es nicht nur um praktische Tipps, die Teilnehmer sollen auch ein paar Lektionen über das Scheitern erhalten. Sie lernen beispielsweise, dass es durchaus in Ordnung ist, zu scheitern, und dass sie im nächsten Anlauf aufgrund ihrer Erfahrung deutlich besser abschneiden werden. Dan Shechtman hält viele Vorträge weltweit zu solchen Themen, manche tragen den Titel ‘Failure? OK, Start Again’.

In einem Interview erklärte Shechtman 2013, dass er sich wie “ein Missionar fühlt, dessen Anliegen die Förderung von Bildung, Wissenschaft und Unternehmertum ist”. Ein wichtiges Anliegen ist ihm auch die naturwissenschaftliche Bildung schon ab dem Kindergartenalter. “Jede Gesellschaft braucht mehr Forscher und Ingenieure, mehr Biologen und IT-Experten”, erklärt er während der Podiumsdiskussion auf der Insel Mainau. “Das sind die Menschen, die neue Unternehmen gründen und eine Gesellschaft wirtschaftlich voranbringen. Aber heute wollen viele junge Menschen diese Berufe nicht mehr ausüben”, bedauert er. “Lieber wollen sie Anwälte oder Buchhalter oder Manager werden.” Das seien zwar alles sinnvolle Berufe, aber eine Gesellschaft aus lauter Anwälten würde nichts produzieren. “Start-Up-Firmen, Hightech-Firmen, kleine Neugründungen die größer werden – das alles wird uns eine bessere Zukunft bescheren,” also mehr Wohlstand für größere Teile der Weltbevölkerung.

 

Sein Eröffnungs-Statement bei der Mainau-Podiumsdiskussion lautete: “Der wichtigste Rohstoff eines Landes, und außerdem der nachhaltigste, ist der menschliche Einfallsreichtum. Diesen Reichtum müssen wir fördern und zwar so früh wie möglich.” Ein starker Satz, und Shechtman hat ihn sich zu eigen gemacht: Im Jahr 2012 begann er in seiner Heimatstadt Haifa, Erzieher und Erzieherinnen weiterzubilden, damit sie ihren Schützlingen wissenschaftliche Themen nahebringen. Aber dieser Ansatz funktionierte nur bedingt, viel ging in der ‘Übersetzungsarbeit’ verloren, in seinen Worten: “Part of it was lost in translation.” Die Erzieher verstanden nicht immer, was sie genau unterrichten sollten und konnten die Inhalte deshalb nicht gut rüberbringen.

Da Shechtman ein Scheitern nie akzeptiert, zog er zwei Schlüsse: Er wollte Kinder dieses Alters direkter ansprechen, und außerdem ein größeres Publikum erreichen. Also half er, ein Programm für Wissenschafts-Kindergärten in Israel auf den Weg zu bringen: der erste eröffnete im Herbst 2015. Zudem kontaktierte er den führenden Bildungs-Fernsehsender Israels und schlug eine Fernseh-Wissenschafts-Show vor. Der Sender griff diese Idee gerne auf: ‘Mit Prof. Dan Wissenschaftler sein’ wurde ins Leben gerufen; auf Hebräisch reimt sich dieser Satz.

Der TV-Sender richtete ihm ein kleines Labor in einem Fernsehstudio ein und stellte Prof. Dan eine Assistentin zur Seite, eine junge Schauspielerin. In jeder der 15-minütigen Sendung diskutieren die Kinder Wissenschaftsthemen mit den Erwachsenen: Wie kann man Dinge messen? Was ist Materie? Wie ist sie aufgebaut? Was verstehen Forscher unter Feldern, vom Magnetismus bis zur Schwerkraft? Man kann sich einzelne Folgen dieser Sendung auf Youtube anschauen, aber da sie ausschließlich mit hebräischen Buchstaben verschlagwortet wurden, sind sie schwer zu finden. Deshalb empfehle ich folgende Links: die Sendung über Materie, über Felder, über Atome und Kristalle, sowie über das Messen. Es ist eine wahre Freude zu sehen, wie leidenschaftlich Prof. Dan den Kindern Wissenschaft erklärt und wie begeistert die Kinder bei der Sache sind.

Diesen Sommer hielt Shechtman einen Lindau-Vortrag mit dem schönen Titel ‘Über die Schönheit und Wissenschaft von Seifenblasen’. Dieser anschauliche Vortrag soll der Ausgangspunkt für eine ganze Vortragsreihe über ‘Forschung und Ästhetik’ werden. Im kommenden Jahr auf dem 67. Nobelpreisträgertreffen möchte er über Kristallographie sprechen, das Themenfeld, in dem er 2011 seinen Chemienobelpreis erhielt.