|The 2010 Wieland Prize went to Croatian scientist Professor Nenad Ban of the Institute of Molecular Biology & Biophysics of the ETH Zurich for his definition of the molecular structures of fatty acid synthases (FAS) in fungi and mammals, the molecular assembly lines for lipid production. His great achievement now allows a precise understanding of how these large, complex biological machines function.|
Heinrich Wieland Prize 2010 goes to Professor Nenad Ban for work on key structures in human fatty acid synthesis
Ingelheim, Munich, Germany, 28 October 2010 - The 2010 Heinrich Wieland Prize went to Prof. Nenad Ban of the Institute of Molecular Biology & Biophysics of the ETH Zurich (Swiss Federal Institute of Technology) for his definition of the molecular structures of fatty acid synthases (FAS) in fungi and mammals, the molecular assembly lines for lipid production. Endowed with prize money of 50,000 euro, this renowned award is one of the most prestigious scientific distinctions in biochemistry and life sciences in Germany. Prof. Ban's work on mammalian fatty acid synthase, one of the most complex enzymes in human cells, is regarded as a milestone in biochemical research.
Beyond its function in cell biology, fatty acid synthase is a potential target for drugs in the treatment of cancer and metabolic disorders such as obesity, making it particularly interesting for medical research. Fatty acids are essential to metabolism in all living organisms. These fatty acids, which are present in the cell membranes, function as energy storage compounds while also serving as messenger molecules. Individual steps in the synthesis have been studied in isolated bacterial enzymes in the past. However, in higher organisms, fatty acid synthesis is catalysed by large multifunctional proteins: many individual enzymes are brought together to form a "molecular assembly line". Following many years of research, Prof. Ban et al. have determined the structures of two representative classes of fatty acid synthases in higher organisms at atomic detail: fungal and mammalian FAS.
These fatty acid synthases represent two different architectural solutions of giant multi-enzymes that shift the products of one enzyme’s active site to the next. Fungal FAS, one of the most complex eukaryotic multi-enzymes, is a large molecule with a mass of 2.6 MDa. The mammalian FAS carries seven functional domains on a single polypeptide chain of approximately 2,500 amino acids and forms a 540,000 Da assembly.
The structures identified by Prof. Ban and his group provide high-resolution structural information on the three-dimensional arrangement of the five catalytic and two non-enzymatic domains of the protein. It also reveals the topology of its linkers and inserted functional domains. The structural insights into FAS can help to understand the dynamic aspects of substrate shuttling in related cellular machines of many multi-enzymes. Prof. Nenad Ban, born in Zagreb, Croatia, studied at the University of Zagreb. He completed his PhD with the Department of Biochemistry, University of California, at Riverside, USA. For his postdoctoral scientific work he joined the Department of Molecular Biophysics and Biochemistry at Yale University in 1995 where he achieved pioneering results with the X-‐ray crystallographic structure of the large ribosomal subunit in the laboratory of Nobel laureate Thomas Steitz. In 2000, he was appointed assistant professor of structural molecular biology at the ETH Zurich, becoming a full professor in 2007. The main goal of his research is to study the structure and function of large cellular assemblies using a combination of crystallographic, electron microscopic and biochemical methods. His research has had a significant impact on the fields of protein synthesis and fatty acid synthesis.
The Board of Trustees of the Heinrich Wieland Prize emphasized the fundamental role of Prof. Ban's work for different fields of research. His work on fatty acid synthase even establishes a direct link to Heinrich Wieland whose student and later son-‐in-‐law Feodor Lynen (Nobel Prize 1964) first identified the eukaryotic fatty acid synthases and characterized the biological reactions. "In truly pioneering work Nenad Ban succeeded in generating high-‐quality crystals from these molecular factories and used them to determine their crystal structure at atomic detail" concluded Prof. Konrad Sandhoff (Bonn), Chairman of the Board. "This great achievement now allows for a precise understanding of how these large, complex biological machines function."
The Heinrich Wieland Prize is named after the German Nobel laureate Prof. Heinrich Otto Wieland (1877 to 1957) and has been awarded every year since 1964. It honours outstanding innovative scientific work in the biochemistry, chemistry, physiology und medical aspects of lipids und other biologically active substances. The prize-winner is chosen by an independent Board of Trustees. The Heinrich Wieland Prize is sponsored by Boehringer Ingelheim. Heinrich Wieland, who was related to the founders of Boehringer Ingelheim, set up the company’s scientific research department.
Professor Nenad Ban winner of the Roessler prize of the ETH Zurich
Nenad Ban from the Institute of Molecular Biology and Biophysics has become the first person to win the Max Rössler Prize. The ETH Zurich professor won the award and 200,000 Swiss francs in prize money for his outstanding teaching and research in the field of molecular structural biology. What can you do to encourage talented professors who are just embarking on a great career in science? Recognize their work and provide ample means for them to conduct free and creative research, according to Professor Peter Chen, Vice-President of Research and Corporate Relations at ETH Zurich. These means should be assigned at a point in the researcher's career where they have the highest impact. With the Max Rössler Prize, ETH Zurich now has an ideal instrument for honoring professors and their achievements. Potential candidates are any ETH-Zurich professors who have been granted a full professorship in the last two years. Moreover, with 200,000 Swiss francs' worth of prize money, the Max Rössler Prize is one of the most highly remunerated advancement awards in Switzerland.
First winner researches giant molecules
The winner of the first Max Rössler Prize is extraordinary in many respects. 43-year-old Nenad Ben, professor of molecular structural biology at the Department of Biology, joined ETH Zurich in 2000 as an assistant professor and became full professor in 2008. Nenad Ban is being honored for his groundbreaking structural analyses of biological macromolecules, which went a long way towards explaining the subunit of a ribosome. As ribosomes play a crucial role in antibiotic resistance, this was a major step in the development of drugs.
Another giant molecule that Ban is researching is fatty acid synthase. Fatty acids are essential for life because, as part of biological membranes, they play an important role in energy storage and signal transduction. Complex protein molecules are responsible for the production of these fatty acids. The detailed structure of fatty acid synthase makes it easy for researchers to find specific weak points against fungal diseases.
Strategic funds for high-quality projects
For Nenad Ban, the Max Rössler Prize is an acknowledgement of the research work of his whole team, which has now been working intensively and successfully together for a number of years. "The prize tops off this period perfectly and marks the beginning of a new one", says Nenad Ban. The prize money is not designated for any project in particular, and the team is free to spend it on their research as they see fit.
The prize was made possible by a donation of 10 million Swiss francs from Max Rössler and the "Max Rössler Funds of the Empiris Foundation" to the ETH Zurich Foundation. The Foundation uses donations to support strategic projects and outstanding scientific talents. An awards committee elects the prize winners from candidates nominated by ETH Zurich. Alumnus and donor Max Rössler explains his involvement by pointing to the importance of providing qualitatively superior education: "Switzerland is more reliant on well-educated, innovative engineers, mathematicians and scientists than ever."
ETH Zurich (Swiss Federal Institute of Technology Zurich) has a student body of fifteen thousand students from 80 nations. More than 360 professors teach mainly in engineering sciences, construction and geomatics, natural sciences and mathematics, system-oriented sciences, management and social sciences, as well as carry out research that is highly valued worldwide. Distinguished by the successes of 21 Nobel laureates, ETH Zurich is committed to providing its students with unparalleled education and outstanding leadership skills.
Professor Nenad Ban
Nenad Ban was born in Zagreb, Croatia and educated at the University of Zagreb where he obtained a BS degree in Molecular Biology and Biochemistry. He obtained his PhD degree in the US at the Department of Biochemistry at the University of California at Riverside (1990-1994) where his research focused on structural immunology and virology. His interest in large macromolecular assemblies led him for his postdoctoral work in 1995 to the Department of Molecular Biophysics and Biochemistry at Yale University where he spearheaded the X-ray crystallographic structure determination of the large ribosomal subunit, a 1.5 MDa ribonucleoprotein complex, and determined its atomic structure in 2000 as part of the group in the laboratory of Thomas Steitz. These results revealed that the active site of the ribosome is formed out of RNA demonstrating that the ribosome is a ribozyme. The structure also opened up new possibilities for the development of new and improvement of existing antibiotics since many clinically available antibacterial drugs inhibit the ribosome. Based on the structure of the large ribosomal subunit the largest biotech startup company Rib-X was established in the US in 2000 and has been operating successfully ever since, developing several new antibiotics that are currently in clinical studies.
In 2000, Nenad Ban was appointed assistant professor of structural molecular biology at the ETH Zurich (Swiss Federal Institute of Technology) becoming full professor in 2007. The main goal of the research in his laboratory is to study structure and function of large cellular assemblies using a combination of crystallographic, electron microscopic and biochemical experiments. This research has significantly impacted two fields, protein synthesis and fatty acid synthesis. In particular, the pioneering structural and mechanistic studies of various ribosomal complexes involved in co-translational protein processing, folding, and targeting provide critical insights into this aspect of ribosomal function. The work on giant multifunctional enzymes involved in fatty acid synthesis offer first mechanistic insights into substrate shuttling and delivery in such megasynthases, with direct implications on our understanding of polyketide synthases and non-ribosomal peptide synthases. Nenad Ban is a member of EMBO and the German Academy of Sciences and the recipient of several prizes and awards including the Roessler prize of the ETH Zurich, the Latsis prize of the Latsis foundation, the Friedrich Miescher Prize of the Swiss Society for Biochemistry, and the AAAS Newcomb Cleveland Prize.
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