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Message from ISCB International Society for Computational Biology Honours Gunnar von Heijne and Ziv Bar-Joseph with Top Bioinformatics/Computational Biology Awards for 2012 Justin Mullins1, BJ Morrison McKay2* 1 Freelance Science Writer, London, United Kingdom, 2 International Society for Computational Biology (ISCB), University of California San Diego, La Jolla, California, United States Gunnar von Heijne (Image 1) decided, tational methods.’’ Polypeptide energetics on whim, to brush up on his rusty, was only the start, however. schoolboy French. He took a few lessons By the early 1980s, molecular biologists and also subscribed to the French popular had begun to determine the sequence of science magazine La Recherche. amino acids in the signal peptides from Flicking through its pages, he came different proteins. However, little had across a short article on protein secretion been done to study the properties of signal Introduction and the signal hypothesis, the mechanism peptide sequences as a group. Each year, the International Society for that describes the way secretory proteins von Heijne changed this. He began Computational Biology (ISCB; http:// cross a membrane. comparing the sequences, looking for www.iscb.org) makes awards for excep- At the time, the late-1970s, very little recurring patterns that might help to tional achievement to two scientists. The was known about this process, but some identify them. ‘‘I looked at 20 to 30 signal ISCB Accomplishment by a Senior Sci- ideas were beginning to emerge. For peptides. Once you did that, some clear entist Award honours career achievement example, it was thought that a so-called patterns emerged that had not been seen in recognition of distinguished contribu- signal peptide—a short chain of amino before,’’ he says. tions over many years in research, acids—at the end of the protein carried He found that small, uncharged amino teaching, service, or any combination of the signal that determined how the acids tended to occupy certain positions in the three. In 2012 this award is going to proteins are transported out of the cell. signal peptide chains, the -3 and -1 Gunnar von Heijne of the Stockholm The article confused him, however. It positions. It is at this site that the signal University in Sweden. The Overton Prize showed a diagram of a hydrophobic signal peptide is later cleaved from the protein recognizes a young scientist in the early to peptide squeezing through the similarly once it has passed through a biomem- mid-stage of his or her career who has hydrophobic membrane. ‘‘That didn’t brane. This pattern has since become already achieved a significant and lasting make sense to me. The hydrophobic known as the (-3, -1)–rule. impact in the field of computational peptide ought to become anchored in the ‘‘Nowadays you would say this was a biology. In 2012, the Overton Prize is membrane,’’ he says. very trivial bioinformatics study,’’ he says being awarded to Ziv Bar-Joseph of The puzzle piqued his interest. He modestly. However, this was an important Carnegie Mellon University in Pittsburgh, solved it by calculating the energetics of discovery and von Heijne’s paper has since Pennsylvania, United States. a polypeptide chain passing through lipid become one of the most highly cited in the The recipients were chosen by the bilayer, which he published in 1979. This field. ISCB’s awards committee chaired by work by a theoretician created ripples in a He then used the newly discovered Alfonso Valencia at the CNIO (Spanish field dominated by experimentalists. patterns to make predictions about pro- National Cancer Research Centre) in And so began the career for which he teins. For example, it became possible to Madrid. The winners will receive their now receives the Accomplishment by a create an algorithm that would take a awards at the ISCB’s annual Intelligent Senior Scientist Award from the Interna- protein sequence and predict whether it Systems for Molecular Biology (ISMB) tional Society for Computational Biology had a signal peptide at the end. meeting, where they will deliver keynote (ISCB). ‘‘Gunnar is one of the big stars of Initially, that was not very useful. When talks. ISMB 2012 (http://www.iscb.org/ our field,’’ says Burkhard Rost, president molecular biologists sequenced a gene or ismb2012) marks the 20th anniversary of of the ISCB. ‘‘He is one of the few who messenger RNA, they generally knew the conference, and will take place July completely change the field using compu- what they were working on; whether it 15–17 in Long Beach, California, United States. Citation: Mullins J, Morrison McKay BJ (2012) International Society for Computational Biology Honours Gunnar von Heijne and Ziv Bar-Joseph with Top Bioinformatics/Computational Biology Awards for 2012. PLoS Comput 2012 ISCB Accomplishment by a Biol 8(5): e1002535. doi:10.1371/journal.pcbi.1002535 Senior Scientist Award: Gunnar Published May 31, 2012 Copyright: ß 2012 Mullins, Morrison McKay. This is an open-access article distributed under the terms of the von Heijne Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Perhaps it all began with the French lessons. As a young PhD student in Funding: JM was paid by ISCB to write this article. theoretical physics at the Royal Institute Competing Interests: The authors have declared that no competing interests exist. of Technology (KTH) in Stockholm, * E-mail: [email protected] PLoS Computational Biology | www.ploscompbiol.org 1 May 2012 | Volume 8 | Issue 5 | e1002535 membrane proteins are the gates and gatekeepers to our cells; they determine what gets in and what stays out,’’ explains Rost. ‘‘That’s why around two-thirds of drugs target membrane proteins.’’ Understanding the structure of trans- membrane proteins provides crucial in- sight into how cells work and is also useful for future drug development. ‘‘That’s why the methods developed by Gunnar are so important,’’ says Rost. To continue his work, von Heijne set up the Stockholm Bioinformatics Centre at the beginning of the millennium. And today, von Heijne runs the Centre for Biomembrane Research in Stockholm, where he has brought together computa- tional, modelling, and experimental groups. Few places can boast the same breadth of experience under one roof. Throughout this time, von Heijne has maintained an impressive work–life balance Image 1. Gunnar von Heijne of Stockholm University. Photo by Max Brouwers. as a scientist, a husband, and a father. He says doi:10.1371/journal.pcbi.1002535.g001 that’s been possible, at least in part, because he was working in a new field with few would have a signal peptide on the end or either in or out. But which orientation competitors. ‘‘I never felt stressed that we’d not. should the protein take? be scooped. I work hard but not crazily.’’ But that changed when sequencing ‘‘We discovered a very simple principle Others clearly admire his positive ap- became faster and biologists started to that determines this,’’ he says. The regions proach, which he combines with a relaxed attitude. ‘‘He also looks ten years younger sequence things they didn’t know much that connect the transmembrane segments than he has any right to!’’ says one envious about. ‘‘The algorithms have continually contain positively charged amino acids, colleague. improved and are now extremely useful,’’ which give them an electric potential. The For a while in the 1980s, he spent half he says. simple principle is that the segments with the his time working as a science journalist for Secretory proteins have to move across greatest number of positive charges end up the Swedish National Radio. ‘‘You decide a lipid bilayer through a molecular inside the membrane, an idea that has since on Monday what you broadcast on Friday machine called a translocon. The signal become known as the ‘‘positive inside rule’’. so there is immediate feedback, which has peptide guides the ribosome that makes ‘‘This is very important work and a good pulse to it,’’ he says. the protein, towards the translocon. This provides some of the best data on But for von Heijne, doing science is triggers the opening of this protein-con- membrane proteins,’’ says Valencia, chair more satisfying than reporting it. ‘‘Radio ducting channel through the membrane. of the ISCB awards committee. stories have a short half life; they’re on air, But other types of protein only make the In the late 1980s, von Heijne began to then they’re gone,’’ he says. ‘‘The rewards journey partway, becoming embedded realise that he could gain significant in science are greater and longer lasting.’’ half in and half out of the membrane. insight into these and other problems by It’s surprising how far schoolboy French These so-called membrane proteins use doing experiments rather than just theory can take you. the same translocon machinery as the work. So he set up his own lab. ‘‘I trained secretory proteins. ‘‘So it was a natural as a chemist so I wasn’t a complete novice 2012 ISCB Overton Prize: Ziv step to start looking at these membrane in a wet lab,’’ he says. proteins next,’’ says von Heijne. This first idea was to see whether it was Bar-Joseph The part of the protein that ends up in possible to make proteins that inserted Ziv Bar-Joseph (Image 2) loves to run. the membrane is very different to the parts ‘‘upside-down’’ into the membrane. He He rises early and hits the streets and trails outside exposed to water. This transmem- could show that by changing the location around Pittsburgh where he lives, often in brane section must be much more hydro- of the positively charged amino acids in a training for a long-distance race.

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