Message from ISCB ISCB Honors Temple F. Smith and Merry Maisel

Introduction sequences. The second is to use the Center at the Boston University College approaches thus developed to identify of Engineering is a superlative resource ages have observed that society structure, function, and regulation in for a wide variety of endeavors.’’ often honors its living DNA, RNA, and proteins. Smith obtained his doctorate in conformists and its dead S The pursuit of these objectives, nuclear physics from the University of innovators; ‘‘but we prefer to honor Smith notes, ‘‘has led to the Colorado in 1969 and was a National living innovators,’’ says Thomas formulation and testing of major Institutes of Health (NIH) postdoctoral Lengauer, professor of computational hypotheses in the areas of molecular fellow with Stanislaw Ulam, T. T. Puck, , director of the Max Planck evolution, gene regulation, and John R. Sadler, studying bacterial Institute for Informatics (Saarbru¨ cken, developmental genetics, and protein genetic regulation. He then took an Germany), and chair of the awards structure–function relationships.’’ The appointment as professor of physics at committee of the International Society success of Smith’s research program Northern Michigan University, for Computational Biology (ISCB). The has been attested to in many ways, not spending summers as a visiting staff committee, composed of a group of least by his receipt of the ISCB’s member in applied mathematics and current and past directors of ISCB Accomplishment by a Senior Scientist theoretical biology at Los Alamos along with previous award recipients, Award for 2007. Scientific Laboratory, with Stanislaw selects honorees for its two annual The award recognizes members of Ulam, George Bell, Walter Goad, Bill awards to innovative scientists. In 2007, the computational biology community Beyer, and, of course, Mike Waterman. the recipients are Temple F. Smith of who have made major contributions to It was there that he helped to organize Boston University (Boston, the field through research, education, GenBank. Massachusetts, United States) and Eran service, or a combination of the three. In 1978–1979, Smith spent a Segal of the Weizmann Institute of It acknowledges community members sabbatical year working with Harold Science (Rehovot, Israel). Smith will who are more than 12 years post- Morowitz at Yale University, exploring receive the 2007 ISCB Accomplishment degree. the relationships among biology, by a Senior Scientist Award, and Segal ‘‘Professor Smith’s contributions go physics, and history. In the following will receive the 2007 ISCB Overton well beyond those for which he is best year, he was a visiting professor at the Prize. known,’’ says Lengauer, ‘‘and he is a University of Southern California. The awards will be presented in towering figure in bioinformatics, one From 1985 to 1991, Smith directed the Vienna, Austria, at the ISCB’s Fifteenth of the founders of the discipline. In Molecular Biology Computational Annual International Conference on addition to starting GenBank and Research Resource of Dana-Farber Intelligent Systems for Molecular being the Smith of the Smith– Cancer Institute, Harvard Medical Biology (ISMB), to be held in Waterman algorithm, he has done School, and Harvard School of Public conjunction with the Sixth European seminal work on the entropy of the Health. Conference on Computational Biology genetic code and on pattern-directed Moving to Boston University in 1991, (ECCB), July 21–25, 2007. protein structure prediction. Other Smith became a professor in the Accomplishment by a Senior influential work includes research on departments of bioengineering and pharmacology and director of BMERC. Scientist Award: Temple F. Smith gene prediction, molecular phylogenies, multiple sequence His center is currently working under The BioMolecular Engineering alignments, and the analysis of NIH and NSF (National Science Research Center (BMERC) at Boston sequence patterns. His results have had Foundation) grants on activation of University, directed by Professor tremendous impact on the field. He has Temple F. Smith (see Image 1), has two been an organizer and co-organizer of major research objectives. The first is the meetings and symposia of the to develop statistical and other multiple disciplines that intersect in Citation: Maisel M (2007) ISCB honors Temple F. computational approaches to the computational biology as well as of Smith and Eran Segal. PLoS Comput Biol 3(6): e128. detection of syntactic and semantic educational and outreach programs for doi:10.1371/journal.pcbi.0030128 patterns in DNA, RNA, and protein young students. Smith feels that the Copyright: Ó 2007 Merry Maisel. This is an open- organizing of the ‘Waterville Valley’ access article distributed under the terms of the Creative Commons Attribution License, which meetings [starting in 1986] was key in permits unrestricted use, distribution, and introducing many younger scientists to reproduction in any medium, provided the original both bioinformatics and the fields of author and source are credited. the older leaders. He has served on Merry Maisel is a freelance science writer based in, undergraduate, graduate, curriculum, San Diego, California, United States of America. E- mail: [email protected]. (General queries and tenure committees as well. And his about the ISCB and its annual awards should be BioMolecular Engineering Research directed to B. J. Morrison McKay: [email protected].)

PLoS Computational Biology | www.ploscompbiol.org0947 June 2007 | Volume 3 | Issue 6 | e128 the next couple of days.’ With a fresh perspective, the team returned to bioinformatics work and published the Smith–Waterman sequence alignment algorithm the following year. It remains one of the most referenced papers in molecular biology.’’ Of his award, Smith says, ‘‘I’m truly honored to join my longtime friend and colleague Mike Waterman, who preceded me in winning this award last year, as well as the distinguished company of previous winners. ‘‘People sometimes date the history of our field back to the algorithm that I Image 1. Temple F. Smith wrote with Mike. I find, instead, that Image 2. Eran Segal (Credit: Kalman Zabarsky, Boston University) the seeds of both computational (Credit: Weizmann Institute of Science) doi:10.1371/journal.pcbi.0030128.g001 approaches and general doi:10.1371/journal.pcbi.0030128.g002 interdisciplinarity were sown somewhat inflammation stress response pathways, earlier—for example, at a Symposium of 10 million basepairs, the chromatin cellular signaling problems (with the on Evolving Genes and Proteins held at is likely to contain about 50,000 Alliance for Cellular Signaling), the Rutgers [University] in 1964 and nucleosomes. The largest genomes are generation of automated models of published in The Quarterly Review of estimated to contain up to 100 billion protein folds, and the core genomics of Biology in March 1966. The problems of basepairs, and the chromatin to the origin of eukaryotes. Smith serves our age are also prefigured in the works package that would need to have 500 on the editorial boards of Molecular of those we count as the great thinkers million nucleosomes, all in the nuclear Biology and Evolution and the Journal of in evolutionary biology: J. B. S. space of a few microns in diameter. Computational Biology. Haldane, D’Arcy Thompson, Sewall But what determines the detailed Interviewed recently by a science Wright, Salvador Luria, and Max positions of nucleosomes along the writer at Boston University, Smith Delbru¨ ck. As I hope to explain in my genome? Such positions are important explained how he and Waterman came keynote address at ISMB/ECCB 2007, for even the most basic cellular to write their only geology paper. It was what is new today in computational processes, including , a serendipitous event, Smith told biology is the wealth of data that we since these processes are carried out by Michael Seele, that occurred when have and the overwhelming complexity the binding of regulatory factors to Waterman visited him at Yale of biological systems as we move ‘‘naked’’ DNA basepairs that are not University. Seele wrote, for an toward future challenges in within nucleosomes. Scientists have upcoming issue of the Boston University bioinformatics.’’ agreed that there must be some College of Engineering Magazine: Last year’s winner of the nonrandom control at work, but there ‘‘As the pair walked to lunch, they Accomplishment by a Senior Scientist has been a lot of argument about just passed through the geology department Award, Mike Waterman, will present what it might be. In the summer of lobby, where two large core samples on the award in Vienna and introduce 2006, Eran Segal (see Image 2) of the display stopped them in their tracks. Temple Smith’s keynote address, titled Weizmann Institute of Science Similar sequences of strata on different ‘‘Computational Biology: What’s (Rehovot, Israel) and colleagues columns were connected by strings. Next?’’ to close the conference on July published a study in Nature (442: 772– Smith and Waterman immediately saw 25, 2007. To read additional 778) hypothesizing that the instructions the columns as strands of DNA and the biographical information and an for wrapping DNA around comparable strata as the short protein abstract of Smith’s keynote address, see nucleosomes are contained in the DNA sequences they were trying to align. http://www.iscb.org/ismbeccb2007/ itself. The authors used a statistical ‘We now faced the possibility that a keynotespresentations/#smith. computational model to predict exactly geologist had solved the problem how that is done, and they completed Overton Prize: Eran Segal before us,’ Smith said. Resigned, Smith the proof by verifying the predictions and Waterman visited the geology As a freshman biology student should with experiments in yeast. chairman and asked how the sequence learn, every eukaryotic organism’s ‘‘This important paper brought Segal alignment had been done. Their mood genome, carried in every somatic cell and his main collaborator, elevated when the chairman informed nucleus, is packaged into a structure experimentalist Jonathan Widom of them that visual observation and string called chromatin. The basic repeating Northwestern University, a lot of were as far as anyone had advanced unit of chromatin is the nucleosome, attention,’’ says Lengauer. ‘‘It was with a solution. ‘Lo and behold! This and each nucleosome consists of featured in Nature’s ‘News and Views’ was an unsolved problem in geology,’ histone proteins around which 147 section in an article by Tim Richmond, Smith said. ‘This resulted in our first basepairs of the genomic DNA are and the work was also described in a geology paper, basically written over wrapped. To accommodate a genome ‘Making the Paper’ section. And it

PLoS Computational Biology | www.ploscompbiol.org0948 June 2007 | Volume 3 | Issue 6 | e128 made The New York Times on July 25. But after idea, result after result, paper Koller and Nir Friedman, and my those of us who attend the ISMB and after paper. Part of it was the long students, colleagues, and RECOMB [Research in Computational hours, but a larger part was that he is collaborators, people without whose Molecular Biology] conferences have an extremely talented and effective efforts no progress could be made. In been aware of Eran Segal for a lot researcher. particular, I am enjoying close longer. Papers written for his doctoral ‘‘Another of his important qualities,’’ collaborations with several thesis have won best paper and best she continues, ‘‘is his ability to produce experimentalists such as Jon Widom, student paper awards at both meetings. meaningful innovations in two distinct Ulrike Gaul, and Howard Chang, and He has introduced very novel ways of disciplines. On the one side, he I’m extremely appreciative of their using statistical learning methods to identifies real biological problems, ability to confirm or refute in vivo the uncover important aspects of the which biologists care about; on the results that emerge from our lab’s regulatory program that is running in other, he comes up with novel effortsinsilico.We,inturn,takecues cells.’’ computational solutions that are well- from their results in revising or ISCB established the Overton Prize founded and technically insightful.’’ adjusting our models. This prize in 2001 in memory of G. Christian Segal spent a year as a research affirms the value of our process.’’ Overton, who was director of the fellow at the Center for Physics and Eran Segal will be given the 2007 Center for Bioinformatics at the Biology at Rockefeller University ISCB Overton Prize in Vienna at ISMB/ University of Pennsylvania and a major before joining the Weizmann Institute ECCB 2007, and he will give a keynote contributor to the field. ‘‘He was a of Science in 2005. ‘‘My lab develops address on July 23. To read additional member of the ISCB Board of quantitative statistical models aimed at biographical information and view an Directors, and his sudden death in 2000 understanding how molecular abstract of his talk, ‘‘Quantitative was a shock to the community,’’ components interact in performing Models for Chromatin and Lengauer said. ‘‘Those of us who complex biological functions,’’ Segal Transcription Regulation,’’ see http:// remember Chris Overton remember says. ‘‘We are interested in the control www.iscb.org/ismbeccb2007/ the kind of work he did—however of transcription and translation and keynotespresentations/#segal. “ laborious it was, it was always exciting the structure of chromatin as it and thought-provoking, dominated by contributes to these. We are currently Additional Information an innovative spark. Eran Segal seems applying our ideas to the to me to be especially deserving of this transcriptional network of the For the full agenda and registration award in Chris’s memory.’’ Drosophila embryo in an attempt to information for ISMB/ECCB 2007, Segal obtained his B.Sc. (summa cum develop thermodynamic models that where these ISCB award winners will laude) in computer science from Tel will explain how cells compute the speak, and where there will be eight Aviv University in 1998. He did his expression patterns of the system from other keynote lectures plus nearly 200 doctoral work in computer science and the cis-regulatory DNA sequence and additional scientific talks, please visit genetics at Stanford University, binding-site preferences of the the conference Web site at http://www. obtaining his Ph.D. in 2004. His advisor, participating transcription factors. iscb.org/ismbeccb2007. For a review of , remembers him vividly. We’re also continuing our work on the past ISCB Accomplishment by a Senior ‘‘One of Eran’s most impressive DNA sequence preferences of Scientist Award and Overton Prize qualities,’’ she says, ‘‘is his ability to get nucleosomes and the way in which they winners, please see http://www.iscb.org/ things done effectively and extremely specify the overall nucleosome ssaa.shtml and http://www.iscb.org/ well. He would be working on five organization.’’ overton.shtml, respectively. ‘‘ Funding. The author was paid by ISCB to projects, and I would be sure that at Of his award, Segal says, I’m very write this article. most one would get done. But not with much honored to be singled out, and I Competing interests. The author has Eran—he just kept producing idea must thank my mentors, Daphne declared that no competing interests exist.

PLoS Computational Biology | www.ploscompbiol.org0949 June 2007 | Volume 3 | Issue 6 | e128