Chemistry

Nobel Prize in Chemistry 2018 – The Evolutionary Tale of Enzymes and Antibodies

Posted on by Judith M. Reichel

This blog post is part of a series of articles on the scientific research that led to this year’s Nobel Prizes. The official Nobel Prize Award Ceremony will take place in Stockholm on 10 December 2018.

Evolution and natural selection – those are the driving forces that turned us from the simple single-celled organisms into the complex, trillion of cells containing beings that we are today. But how could anyone ever ‘harvest’ the ‘power of evolution’? This year’s Nobel Laureates in Chemistry did just that.

The award went to three highly distinguished scientists – half of it was shared by George P. Smith, Professor Emeritus at the University of Missouri-Colombia, and Sir Gregory P. Winter, Professor at the University of Cambridge, UK. The other half was awarded to Frances H. Arnold, biochemist at the California Institute of Technology (Caltech). According to the Nobel Foundation, Frances Arnold received the prize “for the directed evolution of enzymes”. George P. Smith and Sir Gregory Winter were lauded “for the phage display of peptides and antibodies”.

It was in the early 1990s at Caltech where Frances Arnold, born in 1956 in Pittsburgh, first developed what she was now awarded the Nobel Prize for: a method called ‘directed evolution’. This method is used to generate proteins that are not found in nature. Proteins are the building blocks of life. And enzymes, the catalysts involved in pretty much every biochemical reaction, are made up of proteins. Thus, the function of an enzyme and therefore of a biochemical reaction depends on the proteins involved. The structure and function of proteins, in turn, depends on the underlying DNA sequence. In order to generate a specific protein or enzyme function, Arnold induces DNA mutations within a specific DNA sequence of a protein with a function related to her target product. That altered sequence is then introduced back into a host organism or cell culture, where the sequence is translated into a new protein with an altered function. These altered functions are then tested, and the entire process is repeated over and over again until the protein and thereby the enzyme with the desired characteristics and functions is generated. What makes her method stand out is the fact that she is neither trying to design a new enzyme DNA sequence or protein structure from scratch, nor is she waiting for random mutations to introduce alterations that might or might not be useful (as is the case in evolution). Rather, by specifically inducing mutations at areas of interest, she is harvesting the random power of evolution for her benefit. Furthermore, by using rapidly proliferating bacteria as hosts for her newly synthesised DNA sequences, she is also able to quickly assess whether the proteins do in fact exhibit the desired functions – without needing to fully understand the complex co-dependence of protein-structure and its function. Since the beginning of the method in 1993, it has been refined several times and is now the gold-standard for developing new catalysts.

 

 

Another method to produce large amounts of peptides, proteins or antibodies is the so-called ‘phage display’. This method was first developed by George Smith, born in 1941 in Connecticut. The coating proteins of bacteriophages (or ‘phages’, in short), which are viruses that can infect bacteria, can be altered to specifically ‘display’ certain proteins. In 1985, Smith first introduced a protein sequence into a phage and the respective protein was subsequently ‘displayed’ on its surface. Such proteins on the phages are binding sites for peptides or other proteins. If such peptides or proteins bind to them, their binding dynamics and protein-protein interactions can be studied. Moreover, one phage can display several different binding sites. Thus, large libraries of proteins can be screened and selected for their functions and interactions, a process somewhat analogous to natural selection, where the ‘fittest’ version with the most appropriate functions survive or are ‘selected’.

 

 

Finally, if the DNA sequence of a protein is known, this can be introduced onto the surface of the phage. If a peptide then binds to this surface protein, that specific binding site can be isolated and its genetic code be sequenced; this way a new antibody can be identified and subsequently generated in the lab.

Last but not least, Gregory P. Winter, born in 1951 in the Leicester, UK, developed this intricate method of phage display even further to produce new pharmaceuticals. Because of his improvements, many antibodies intended for human use no longer needed to be synthesised in mice or other host species, thereby minimising cross- and allergic reaction. Winter was so successful with his new antibody developing tool that he founded ‘Cambridge Antibody Technology’ in 1989 – one of the first biotech companies involved in antibody engineering. The first pharmaceutical antibody developed with this method was approved in 2002. It is an antibody to TNF alpha, a part of the inflammatory response, and is used to treat rheumatoid arthritis, psoriasis and inflammatory bowel diseases. It was the world’s top selling pharmaceutical in 2017 with sales over USD 18bn.

However, phage display as used by Winter is not only useful for broad diseases that affect all patients in a similar way. It has also become a very promising approach to treat (metastatic) cancers: Phage display is used to create and select synthetic antibodies that target the surface proteins of the tumour. These are then made into synthetic receptors for T-Cells collected from the patient, another essential part of the immune system. Thus, the patient’s own immune system is then able to recognise and fight the cancer cells, a process particularly useful for treating metastatic cancers.

Additional information: A new series of Mini Lectures concerning DNA and its replication and modification can be watched in our mediatheque. 

Thomas A. Steitz 1940–2018

Posted on by LiNo News

Thomas Steitz with young scientists at the Lindau Nobel Laureate Meeting 2018. Photo/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

The Council and Foundation Lindau Nobel Laureate Meetings deeply mourns the loss of laureate Thomas Steitz, who sadly passed away on 9 October 2018 at the age of 78. He received the 2009 Nobel Prize in Chemistry for his studies on ribosomes.

Steitz completed his Ph.D. in biochemistry and molecular biology at Harvard University in 1966. After research stays in Europe, he moved back to the US. He was a Sterling Professor of Molecular Biophysics and Biochemistry and Professor of Chemistry at Yale University.

Thomas Steitz participated in four Lindau Nobel Laureate Meetings, only recently in 2018. The Council and Foundation extend their deep sympathies to Thomas Steitz’ family.

2018 Nobel Prize in Chemistry

Posted on by LiNo News

2018 Nobel Laureates Frances H. Arnold, George P. Smith and Sir Gregory P. Winter. Illustration: Niklas Elmehed. Copyright: Nobel Media AB 2018.

On Wednesday, 3 October 2018, the Royal Swedish Academy of Sciences has awarded the Nobel Prize in Chemistry 2018 to Frances H. Arnold “for the directed evolution of enzymes”  and to George P. Smith and Sir Gregory P. Winter “for the phage display of peptides and antibodies”.

Find out more about the 2018 Nobel Prize in Chemistry here.

The Power of Evolution: Nobel Prize in Chemistry 2018

Posted on by LiNo News

Today, the Royal Swedish Academy of Sciences announced the 2018 Nobel Laureates in Chemistry. Frances H. Arnold (USA) received one half of the prize “for the directed evolution of enzymes”; the other half of the prize was awarded to George P. Smith (USA) and Sir Gregory P. Winter (UK) “for the phage display of peptides and antibodies”.

2018 Nobel Laureates Frances H. Arnold, George P. Smith and Sir Gregory P. Winter. Illustration: Niklas Elmehed. Copyright: Nobel Media AB 2018.

From the press release of the Royal Swedish Academy of Sciences:

“The power of evolution is revealed through the diversity of life. The 2018 Nobel Laureates in Chemistry have taken control of evolution and used it for purposes that bring the greatest benefit to humankind. Enzymes produced through directed evolution are used to manufacture everything from biofuels to pharmaceuticals. Antibodies evolved using a method called phage display can combat autoimmune diseases and in some cases curemetastatic cancer.”

Read more about the 2018 Nobel Prize in Chemistry here.

A Long Road to Becoming a Chemist

Posted on by Ana Torres

The path to my professional career as a chemist was not easy but constructive and challenging in some ways. I grew up in a small, quiet and traditional town in the state of Mexico Texcoco. Both of my parents had to overcome severe economic difficulties to pursue their own career in biology. Thankfully, I was blessed with their pledge to provide me a good education.

I attended a private school to learn English and because the academic programme was more challenging. During my basic education, I participated in several science and academic contests and I enjoyed the school profoundly. My generation was the first that stayed at home, there were not more chances to play in the streets or the neighbourhood, because of the numerous cars in the streets and the worsening of security. Then, in the middle school, I attended a math workshop where I learned tricks to do arithmetic operations in a flash and to solve math puzzles. With that training, I was selected to participate in Math Counts and the Pierre Fermat contest. Later, I enrolled in the EPT-UAEM public high school and was benefitted with a scholarship. During my last year there, I was invited to train for the regional Chemistry Olympiads. I was selected to continue to the state and furthermore the national contest.  That stage was meaningful for my further decision to study chemistry since I was selected to attend Mexico’s National Olympiad of Chemistry. This privilege implied a strong commitment by means of travelling two hours to the school of Chemistry of UAEM-Mexico to be trained for the competition, and then two hours more for the way back. I travelled with my mother after the school in an old van provided by the principal two or three days a week during some months. We arrived at home almost at midnight, exhausted but enthusiastic about my training and the hopeful support within my family. I valued that experience greatly because other peers and I received fascinating lessons with devoted teachers and scientists.

 

Photo: Courtesy of Ana Torres

Ana Torres in front of the Rudder Fountain on the Texas A&M University campus, Photo: Courtesy of Ana Torres

 

After the enriching experience of attending the national contest and motivated by my teachers I decided to study chemistry in the School of Chemistry of the National Autonomous University of Mexico. So therefore, I spent four hours on a round-trip each day to Mexico City to pursue my bachelor degree. Sometimes I travelled by car with my father before dawn, but other days I had tiring trips in the overcrowded subway and the bus, which arrived in the middle of nowhere, where my parents picked me up. Fortunately, quantum chemistry captivated me and I joined a theoretical research workgroup after I had my first course in that subject area.

One year later, I got my bachelor degree with honours and continued my postgraduate studies in chemistry supported by a grant of the National Council of Science and Technology. Usually, there are very few students willing to pursue a career in Theoretical Chemistry in my program. It is worth mentioning that while I studied, my advisor and other theorists designed the Quantum and Computational Chemistry post-graduate courses – indeed some of the lectures were given for the very first time. Furthermore, at that time I started my own family and I had to organise my time efficiently to get a functional balance between motherhood, research and teaching. Therefore, through family shared efforts, hard-work and passion for science I graduated with honours, gaining the M.Sc. and Ph.D. degrees in chemistry, whereas my son developed a love for math.

 

Ana Torres with her parents, Photo: Courtesy of Ana Toores

Ana Torres with her parents, Socorro Hernandez and Pablo Torres, at the National Autonomus Unviersity of Mexico, Photo: Courtesy of Ana Torres

 

I became a teacher and mentor for undergraduate students just after I got my Master’s degree. Then, for the Ph.D., I moved to the Materials Research Institute where Prof. Serguei Fomine became my advisor. From him I learned a strong discipline of work and a structured way to analyse the chemical problems. This contributed positively since I graduated in less time than my postgraduate program demarked. After I graduated, I was accepted for a postdoctoral position within the group of Prof. Perla Balbuena in Texas A&M University. Thus, I dealt with almost six months of paperwork to get a scholarship and arrange the immigration documentation for my son, my husband and for me. I arrived in the US one month later than the start date of the programme given the migratory issues. At present, I am grateful for the support and academic guidance of Prof. Balbuena and committed to work hard on my research project. My family and I are partaking this opportunity to grow in academic and personal areas and I shall respond to their great effort. Science has opened me the doors to travel to countries abroad and to build collaborations and friendships. Currently, I am member of the Graduate Women in Science organisation, the Toastmasters club as well as the group of Bible studies for women and I enjoy sharing Spanish classes.

 

Lindau Alumni 2017 Ana Torres and Octavio Saucedo, Nobel Laureate Mario Molina, former President of the Mexican Academy of Sciences Jose Franco and Director of International Cooperation CONACYT, Arturo Borja (from left to right) after a discussion on Public Policy at the 67th Lindau Meeting, Photo: Courtesy of Ana Torres

Lindau Alumni 2017 Ana Torres and Octavio Saucedo, Nobel Laureate Mario Molina, Jose Franco, former President of the Mexican Academy of Sciences, and Arturo Borja, Director of International Cooperation CONACYT, (from left to right) after a discussion on Public Policy at the 67th Lindau Meeting, Photo: Courtesy of Ana Torres

 

The main goal of my current research project is to perform a theoretical study of the interfacial phenomena relevant for the development of new generation rechargeable batteries. Likewise, I will address the confinement effect exerted by molecular sieves, solvents, nano-structured materials or an inert gas matrix over the chemical reactions, which are important for chemical catalysis. It is expected that the outcome of this project would support experimental research that has been developed for both the description and design of battery materials and catalytic systems. Nowadays, it is important to assist the novel frontier materials design (with enhanced features) using theoretical methods and computational calculations before being synthetised in the laboratory. This could be very helpful to optimise resources and facilitate the materials implementation for the manufacturing process of technological devices.

From Copper Photocatalysts to Chemical Topology

Posted on by Melissae Fellet

When Jean-Pierre Sauvage started his own research lab, he focused on developing copper catalysts that could absorb light and use that energy to split water into hydrogen and oxygen gases. After characterising the shape of one of these catalysts, the focus of his research changed to that recognised by the 2016 Nobel Prize in chemistry: synthesising molecules with interlocking rings and knots.

The game-changing catalyst was a copper ion binding to the concave portions of two crescent-shaped phenanthroline molecules. Because of its binding geometry, the copper ion held the arcs in perpendicular planes. Sauvage realised that closing each crescent to form a loop would create a molecule with two interlocking rings, called a [2]catenane. “At that stage, we had to decide whether we would continue in the field of inorganic photochemistry, or be more adventurous and jump into a field we didn’t know so well,” Sauvage said. “We decided to jump.”

 

Jean-Pierre Sauvage during his lecture at the 67th Lindau Meeting, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

Jean-Pierre Sauvage during his lecture at the 67th Lindau Meeting, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

The field less familiar to him at that time is called chemical topology, and it has foundations in mathematics and biological molecules. Topology is the study of infinitely deformable objects. Mathematicians classify topological knots as identical if they have the same number of loops and crossings, even if their shapes appear drastically different. Topological knots can also be found in biological structures. Some bacteria have a loop of DNA, and two interlocking rings of nucleic acid can appear as an intermediate during cell replication. In viruses that infect bacteria, intertwined cyclic proteins can provide rigidity to their outer shells.

In 1961, H. L. Frisch and E. Wasserman, at Bell Labs, connected topology to the chemical world, publishing ideas to synthesise molecules with interlocking rings and knots. Three years later, Profs. Schill and Lüttringhaus synthesised the first molecule with two interlocking rings, in an elegant, but lengthy, process that built each ring of the [2]catenane sequentially.

About twenty years later, Sauvage recognised that his copper catalyst pre-assembled the interlocking portion of the catenane, providing a fast and efficient route to the simplest molecular chain. In 1983, he, along with Christiane Dietrich-Buchecker and J.P. Kintzinger, synthesised a [2]catenane in two steps, compared to the 15 steps needed in the previous synthesis. Sauvage says the researchers knew their work was novel, but they partly hid it in the literature, publishing in a lesser-read journal and writing the article in French. Although the paper remains one of the few French papers of his career, the concept of templating catenane synthesis has become a standard method in the field.

 

A molecule with interlocking rings syntheised by Jean-Pierre Sauvage and Christiane Dietrich-Buchecker in 1983. Credit: Wikimedia Commons

A molecule with interlocking rings synthesised by Jean-Pierre Sauvage and Christiane Dietrich-Buchecker in 1983. Credit: Wikimedia Commons

Over the next decade, Sauvage and his group synthesised and characterised molecules with more complex topologies, including a doubly-interlocking catenane and molecular trefoil knot with three loops and three crossings.

As the researchers continued to follow their interest in the challenge of making molecules with novel structures, they also developed an interest in molecular motion. In interlocking rings, for example, one ring can rotate around the other. With a reliable way to make a variety of interlocking molecules, researchers could then build new structures, experiment with ways to control the motion, and then convert that motion to work in molecular machines – advances achieved by Sauvage’s colleagues, co-laureates, and friends J. Fraser Stoddard and Bernard L. Feringa.

From the story of his research, Sauvage had four pieces of advice for the young scientists:

Novelty is the most important thing when choosing research, and he stressed the importance of working in a team, interacting with other scientists inside or outside your group. Moving to an unfamiliar field can be very beneficial, Sauvage said. And although that jump can be intimidating, he encouraged the young scientists to be self-confident: “Do not ask yourself whether you are good enough to tackle a new problem: Just do it!”

#LiNo17 Daily Recap – Thursday, 29 June

Posted on by Laura Schönhardt

Thursday was the last day in Lindau but not the last day of the meeting. Friday is going to take the participants to Mainau Island, so while they are enjoying their last day on the picturesque island, let’s take a look at what happened yesterday. Here are our highlights from Thursday:

 

Video of the day:

All six panelists – Nobel Laureates Sir John E. Walker and Dan Shechtman, Wiltrud Treffenfeldt (Chief Technology Officer of Dow Europe GmbH), May Shana’a (Head of Research & Developmen of Beiersdorf AG) and young scientist Thomas L. Gianetti from ETH Zurich as well as chairwoman Alaina G. Levine – have strong opinions on “Science Careers” and gave excellent advise for #LiNo17 participants.

You are welcome to browse through our mediatheque for more panel discussions, lectures and other informative videos.

 

Picture of the day:

Nobel Laureate Peter Agre’s lecture on “Aquaporin Water Channels” was not only educational, but also made the young scientists laugh. Most definitely one of the best pictures of Thursday.

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Audience in Peter Agre's lecture

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

When Nobel Laureates come to Lindau, photographer Volker Steger presents each with a surprise task. Find out what it is and how the laureates “sketch their science”.

Sketches of Science Slider

Do take a look at more of our inspring blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

We will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

 

#LiNo17 Daily Recap – Tuesday, 27 June 2017

Posted on by Laura Schönhardt

We are already three days into this year’s chemistry meeting and there are so many interesting things happening. We have collected a huge amount of exhilarating pictures, exceptional lectures and thought-provoking blog contributions. So you can guess that there is so much more that you should definitly check out on our mediatheque than we present to you in our daily recap . Enjoy the following highlights!

 

Video of the day:

“This meeting is about mentorship, and it’s about the future, it’s not about the Nobel Laureates, it is [in fact] about mentoring the next generation of scientists – OUR BEST HOPE FOR THE FUTURE” – Brian Malow has provided us with a live video featuring seven young scientists.

 

 

Picture of the day:

After having the Poster Flashes on Monday, our Poster Session proved to be a success. Frank Biedermann, a young scientist explaining his research about “Supramolecular Sensing Ensembles” to Nobel Laureate Erwin Neher.

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Poster Session

 

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

“When scientific issues become publicly controversial, Nobel Laureates have a history of making strong statements at the Lindau Nobel Laureate Meetings,” writes Melissae Fellet in her new article on science in a post-truth era. Politics and the question of what scientists can do to rebuild trust is one of the main topics being discussed by the participants of the 67th Lindau Meeting.

Post-truth_Slider

Press Talk on ‘Science in a Post-Truth Era’ hosted by Deutsche Welle during the 67th Lindau Meeting. Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Do take a look at more of our exciting blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

 

Over the course of the next four days, we will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

#LiNo17 Daily Recap – Monday, 26 June 2017

Posted on by Laura Schönhardt

Yesterday, the scientific programme of the 67th Lindau Nobel Laureate Meeting commenced. It was a fantastic day full of science and exchange – this short recap can only give you a glimpse of everything that happened, but for us the following are our personal highlights!

 

Video of the day:

The first of today´s many inspirational lectures was the one given by Bernard L. Feringa, 2016 Nobel Laureate in Chemistry. He took the young scientist on a journey into the world of molecular switches and motors, the process of discovery and his personal experiences through his scientific career. In particular, he addressed how fundamental questions and molecular beauty have guided him on this journey.

 

Picture of the day:

Nobel Laureate Martin Chalfie enjoys interacting with young scientists.

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings, Young Scientists in talk with Martin Chalfie

 

 

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog post of the day:

Mexico hosted the International Day on Monday. A good reason for us to feature a young scientist from Mexico, Ana Torres, who said: “I urge each woman […] to play an active role in our nation.”

Do take a look at more exciting blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

 

Over the course of the next five days, we will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

#LiNo17 Daily Recap – Sunday, 25 June 2017

Posted on by Laura Schönhardt

“I close my remarks by asking the young students gather this week at the Lindau Nobel Laureate Meeting to consider joining the effort to combat climate change.” – Steven Chu

Yesterday, the 67th Lindau Nobel Laureate Meeting started in grand fashion with the festive opening ceremony featuring the warm and heartfelt welcome address by Countess Bettina Bernadotte and a very poignant and moving keynote by Steven Chu. The Nobel Laureate himself was, unfortunately, unable to attend, but his fellow laureate William E. Moerner luckily stepped in to deliver the powerful speech on “Science as an Insurance Policy to the Risks of Climate Change”.

 

Video of the day:

“A changing climate does not respect national boundaries.”
First highlight is Steven Chu’s keynote, read by William Moerner. Chu addressed the highly topical issue of climate change and reminded all of us how important it is to treat the earth well.

Obviously, this is not the only video from yesterday and today! You are more than welcome to browse through our mediatheque for more.

 

Picture of the day:

Standing Ovations
William Moerner’s presentation of Steven Chu’s keynote was one of the most moving moments.

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, Germany

67th Lindau Nobel Laureate Meeting, 25.06.2017, Lindau, Germany

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog post of the day:

“A Stellar Meeting Where the Stars Shine Bright, the Science Is Chill, and the Networking Is Chem-Tastic.”
Another highlight is the blog post from science writer Alaina G. Levine. She is back in Lindau for #LiNo17 and gives a preview of the panel discussion on science careers that she will chair on Thursday (replacing Karan Khemka).

Do take a look at more exciting blog posts.

 

Tweets of the day:

 

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

 

Over the course of the next six days, we will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.