From DNA Sequences to Living Systems

ISSN: 1050–6101, Issue number 47 Vol. 11, Nos. 3–4, July 2001

In This Issue From DNA Sequences to Living Systems

In the News Genomes to Life, Microbial Cell Project—Complementary New DOE Programs Explore Critical Life Processes Genomes to Life ...... 1 OASCR and GTL...... 1 he complete DNA sequences for organisms ranging from humans to mice Tand microbes are presenting an even greater scientific challenge—to under- DOE Microbial Cell Project ...... 2 stand how life’s component parts function together and are influenced by envi- Human Genome Draft ...... 3 ronmental factors in creating and operating dynamic living systems. DOE, a Genomes: A Perspective...... 5 key player in the genomics revolution, is poised to make important contributions to this next grand scientific quest through the Microbial Cell Project (MCP) Honor for DeLisi ...... 5 and the proposed Genomes to Life (GTL) program. New NIH Institute...... 6 Structural Genomics ...... 7 The MCP takes a whole-genome development of appropriate tools. The approach to understanding the func- two programs will formulate more Synchrotron Use...... 7 tion and regulation of all genes for a high-throughput methodologies for Proteome Organisation...... 7 single living system and the pathways simultaneously studying many compo- Breast Cancer Research ...... 8 in which the protein products interact. nents of living systems. The MCP will play a leading role in The extraordinary applications of this Nuclear Medicine...... 13 GTL, DOE’s major new undertaking. Toxicogenomics Center...... 14 holistic approach will help DOE fulfill The GTL will build on previous Office its broad missions in energy, environ- Kettering Prize ...... 14 of Science research that includes the mental remediation, and protection of Zeta Phi Beta Conference ...... 15 Human Genome Program and the human health. [For more details on Microbial Genomes...... 18 Microbial Genome Program initiated GTL, see color centerfold and http:// in 1994. The plan for GTL is to use DOEGenomesToLife.org; for informa- Sloan-DOE Fellowships...... 21 DNA sequences from both microbes tion on MCP, see article, p. 2, and à See color centerfold about GTL and higher organisms, including http://microbialcellproject.org.] between pages 12 and 13. humans, to systematically tackle questions about essential life pro- Comparative Genomics cesses conserved across species. OASCR Joins OBER Sushi Delicacy ...... 8 Advanced technological and computational resources tested in Genomes to Life Program Arabidopsis Sequence...... 9 and modeled in the MCP will he DOE Office of Biological and Envi- AAAS Prize...... 9 be used to identify and under- Tronmental Research (OBER) and Office Microbial Conference...... 9 stand the underlying mecha- of Advanced Scientific Computing Research nisms that enable organisms Mouse and Resources...... 10–12 (OASCR) have formed a strategic alliance to to function in diverse environ- meet the challenges of studying complex sys- Resources mental conditions. tems. OASCR fosters and supports funda- Next-Generation Computing....17 In a sense, the MCP is advance mental research in advanced scientific HGMIS Resources...... 19 reconnaissance for GTL, and computing and computational science—applied mathematics, computer sci- Other Resources ...... 19–23 the two programs are and will remain closely entwined. ence, and networking—and operates For Your Information supercomputer, networking, and related facil- Both GTL and the MCP con- ities. These tools enable researchers to ana- Event, Training Calendars 22–23 tribute toward the shifting of lyze, model, simulate, and predict complex biology to a more quantitative phenomena relevant to DOE’s biological mis- Funding Information...... 23 science, involving the collection, Subscription, Requests...... 24 sions. The proposed Genomes to Life program integration, and dissemination fits readily into this portfolio.à Acronyms...... 24 of diverse data and the

All issues of Human Genome News are online (www.ornl.gov/hgmis/publicat/hgn/hgn.html). 2 Human Genome News 11(3–4) July 2001

In the News

In addition to working with academic, DOE Microbial Cell Project nonprofit, and industrial partners, A Perspective by Daniel Drell DOE will take advantage of the scientific capabilities of its national ore than 50 scientists from such other disciplines laboratories. These capabilities Mcomplete as engineering; chemistry; physics; include high-throughput genomic microbial genome and the computer, imaging, and even DNA sequencing, microbial biochemistry and array development and sequences have management sciences. been deciphered analyses; physiology; very high resolu- since the publica- Why Microbes? tion imaging; and structural biology. tion of the first in National user facilities such as 1995. These Microbes have evolved for 3.7 billion synchrotrons will play important sequences offer years and have colonized almost every roles, as will high-performance computing. scientists an Daniel Drell environment on earth. In the process, unprecedented DOE Human they have developed an astonishingly The MCP’s ultimate aim is to learn opportunity to Genome Program diverse collection of capabilities that enough about cellular functions so study cellular life in can be used to help DOE meet its chal- they can be manipulated knowledge- its simplest form lenges in toxic-waste cleanup, energy ably to enhance beneficial and sup- and to begin understanding how nature production, global climate change, and press unintended effects. MCP orchestrates the activities of living biotechnology. planners are well aware that it is systems. Additionally, their internal organiza- premature to explore manipulations This opportunity is at the root of DOE’s tion and complex regulatory systems or interventions. Given the complexity new Microbial Cell Project (MCP), allow microbial cells to adapt to a myr- of metabolic networks in even the begun in 2001 by the Office of Science’s iad of environments. They work as simplest cell, such actions would be offices of Biological and Environmental miniature chemistry laboratories, analogous to throwing the proverbial Research (OBER) and Basic Energy making unique products and carrying monkey wrench into a complex Sciences (OBES), allied with the Office out functions specific to their environ- machine; the outcomes most likely of Advanced Scientific Computing mental conditions. would not be useful and informative. Research (OASCR). OBER and OBES When greater knowledge is gained Understanding the complex function- contributed $12 million and OASCR about the parts, their interactions, ing of a single microbial cell ultimately $3 million through its Advanced the functional pathways to which will enable science to go far beyond Modeling and Simulation of Biological they belong, their partners in bio- just exploiting the beneficial capabilities Systems Program. chemistry, and their temporal and of microbes to meet DOE’s missions. spatial distribution within the cell, The challenges are great. Although the Much of the knowledge gained will these interventions—if and when complete list of life’s working parts for apply to cells in all living organisms. they merit exploratory research— sequenced genomes is now online, many The MCP thus represents a first step can be more precise and predictable. perform unknown functions. Addi- in moving from cataloguing molecular tionally, little is understood about how parts to constructing an integrative The MCP is as bold and major an and when the parts function together in view of life at the level of a whole undertaking as DOE’s Human living cells and respond to environmen- organism—microbe, plant, or animal. Genome Initiative was in 1987. tal changes. Gaining an understanding Much of the MCP’s research appeal of the complexities of systems-level Goals stems from the simple fact that this is where the science is leading. Like functioning also requires new ways of The MCP has four main goals: thinking and collaborations with fortunate children with their first Determine how microbial proteins Lego set who have seen the pictured combine into molecular machines item and know it can be built, we * Image Galleries that fulfill many of life’s important have opened the box and found the intracellular processes. pieces. The instructions are missing, High-quality, original graphics can be however, so we must complete the Characterize the internal cell environ- downloaded from the HGMIS Web site. construction through experimenta- ment and its effects on the proteins No permission is needed, but please let tion. Fortunately, we can build on HGMIS know where they were used. and protein machines that perform decades of intense biological Human Genome Project Information: functions relevant to DOE missions. research to make the job easier. www.ornl.gov/hgmis/graphics/ Characterize the intracellular dis- slides/images1.html tribution, quantities, and fluxes of The MCP makes its first grant awards Genomes to Life Program: the proteins and protein machines this summer. A list will be available via http://doegenomestolife.org/ inside a microbial cell. the Web (http://microbialcellproject. gallery/images1.html org/funding) and will be the subject Please cite the U.S. Department of Use high-end computing to model of an article in the next issue of Energy Human Genome Program and gene-to-gene, gene-to-protein, and HGN. [Daniel Drell, 301/903-4742, list the Web site’s home page.à protein-to-protein interactions and [email protected]] à the cell’s internal biochemistry. July 2001 Human Genome News 11(3–4) 3

In the News Human Genome Working Draft: First-Edition Travel Guides

n February, scientists from the pub- genome sequencing centers produced The total number of genes is esti- Ilic Human Genome Project and the over 22.1 billion bases of raw mated at 30,000 to 35,000—much private company Celera Genomics sequence data, comprising overlap- lower than previous estimates of published the long-awaited details of ping fragments totaling 3.9 billion 80,000 to 140,000 that had been the working-draft DNA sequence bases and providing sevenfold cover- based on extrapolations from gene- achieved less than a year before. age (sequenced seven times) of the rich areas as opposed to a composite Although the draft is filled with mys- human genome. Over 30% is high- of gene-rich and gene-poor areas. teries, the first panoramic view of the quality, finished sequence, with eight- human genetic landscape has to tenfold coverage, 99.99% accuracy, Almost all (99.9%) nucleotide bases revealed a wealth of information and and few gaps. All data are freely are exactly the same in all people. some early surprises. Papers describ- available via the Web (www.ornl.gov/ The functions are unknown for over ing research observations in the jour- hgmis/project/journals/sequencesites. 50% of discovered genes. nals Nature (Feb. 15) and Science html). (Feb. 16) are freely accessible via the The Wheat from the Chaff The entire working draft will be fin- Web (www.ornl.gov/hgmis/project/ Less than 2% of the genome codes ished to high quality by 2003. Coinci- journals/journals.html). for proteins. dentally, that year also will be the Although clearly not a Holy Grail or 50th anniversary of Watson and Repeated sequences that do not code Rosetta Stone for deciphering all for proteins (“junk DNA”) make of biology—two early metaphors up at least 50% of the human commonly used to describe the genome. coveted prize—the sequence is a magnificent and unprecedented Repetitive sequences are resource that will serve as a thought to have no direct func- basis for research and discovery tions, but they shed light on throughout this century and chromosome structure and beyond. It will have diverse prac- dynamics. Over time, these tical applications and a profound repeats reshape the genome by impact upon how we view our- rearranging it, creating selves and our place in the tapes- entirely new genes, and modi- try of life around us. fying and reshuffling existing genes. One insight already gleaned from Reprinted by permission from Nature (Feb. 15, the sequence is that, even on the 2001). Copyright 2001 Macmillan Magazines Ltd. During the past 50 million molecular level, we are more Reprinted with permission from Science years, a dramatic decrease than the sum of our 35,000 or so (Feb. 16, 2001). Copyright 2001 American seems to have occurred in the genes. Surprisingly, this newly Association for the Advancement of Science. rate of accumulation of repeats estimated number of genes is in the human genome. only one-third as great as previ- Crick’s publication of DNA structure How It’s Arranged ously thought and is only twice as that launched the era of molecular The human genome’s gene-dense many as those of a tiny transparent genetics (www.nature.com/genomics/ “urban centers” are predominantly worm, although the numbers may be human/watson-crick). Much will composed of the DNA building revised as more computational and remain to be deciphered even then. blocks G and C. experimental analyses are performed. Some highlights from Nature, Science, At once humbled and intrigued by and The Wellcome Trust follow In contrast, the gene-poor “deserts” this finding, scientists suggest that (www.ornl.gov/hgmis/project/ are rich in the DNA building blocks the genetic key to human complexity journals/insights.html). A and T. GC- and AT-rich regions lies not in the number of genes but in usually can be seen through a how gene parts are used to build dif- What Does the Draft Human microscope as light and dark bands ferent products in a process called Genome Sequence Tell Us? on chromosomes. alternative splicing. Other sources of added complexity are the thousands of By the Numbers Genes appear to be concentrated in random areas along the genome, post-translational chemical modifica- The human genome contains tions made to proteins and the reper- with vast expanses of noncoding 3164.7 million chemical nucleotide DNA between. toire of regulatory mechanisms bases (A, C, T, and G). controlling these processes. Stretches of up to 30,000 C and G The average gene consists of 3000 bases repeating over and over often The draft encompasses 90% of the bases, but sizes vary greatly, with human genome’s euchromatic portion, occur adjacent to gene-rich areas, the largest known human gene being forming a barrier between the which contains the most genes. In dystrophin at 2.4 million bases. constructing the working draft, the 16 genes and the “junk DNA.” Theseß 4 Human Genome News 11(3–4) July 2001

In the News

CpG islands are believed to help reg- HGP Sequenced Genomes ulate gene activity.

Chromosome 1 has the most genes Organism Size Yr. No. of Gene (2968), and the Y chromosome has (Mb) Seq. Genes* Density** the fewest (231). Saccharomyces cerevisiae yeast (eukaryote) 12.1 1996 60341 483 How the Human Compares Escherichia coli bacterium (prokaryote) 4.6 1997 42002 932 with Other Organisms Caenorhabditis elegans roundworm (eukaryote) 97 1998 19,0991 197 Unlike the human’s seemingly random distribution of gene-rich areas, Arabidopsis thaliana plant (eukaryote) 100 2000 25,0001 221

many other organisms’ genomes 1 are more uniform, with genes Drosophila melanogaster fruit fly (eukaryote) 180 2000 13,061 117 evenly spaced throughout. Homo sapiens human (eukaryote) 3000 2000 35,000– 12 draft 45,0001 Humans have on average three times as many kinds of proteins as Sources the fly or worm because of mRNA 1. Nature 409, 819 (Feb. 15, 2001) (www.nature.com/nature/journal/v409/n6822/fig_ transcript “alternative splicing” tab/409818a0_F1.html) and chemical modifications to the 2. Entrez Genomes (www.ncbi.nlm.nih.gov/PMGifs/Genomes/micr.html) proteins. This process can yield dif- *Gene predictions are made by computational algorithms based on recognition of gene- ferent protein products from the sequence features and similarities to known genes. Current gene estimates await fur- same gene. ther confirmation, including characterization of their protein products and functions. **Gene density = Number of genes per million sequenced DNA bases. Humans share most of the same protein families with worms, flies, and plants, but the number of gene fam- ily members has expanded in humans, Applications, Future With whole-genome sequences and especially in proteins involved in Challenges new high-throughput technolo- development and immunity. gies, they can approach questions Deriving meaningful knowledge from systematically and on a grand The human genome has a much the DNA sequence will define research scale. They can study all the greater portion (50%) of repeat through the coming decades to inform genes in a genome, for example, sequences than the mustard weed our understanding of biological or all the transcripts in a particu- (11%), the worm (7%), and the fly (3%). systems. This enormous task will lar tissue or organ or tumor, or require the expertise and creativity of how tens of thousands of genes Although humans appear to have stopped tens of thousands of scientists from and proteins work together in accumulating repeated DNA over 50 varied disciplines in both the public interconnected networks to million years ago, there seems to be no and private sectors worldwide. orchestrate the chemistry of life. such decline in rodents. This may account for some of the fundamental differences The draft sequence already is having Post-sequencing projects are well between hominids and rodents, although an impact on finding genes associated under way worldwide (see related gene estimates are similar in these spe- with disease. Over 30 genes have been articles, pp. 1 and 7). These explo- cies. Scientists have proposed many the- pinpointed and associated with breast rations will result in a more com- ories to explain evolutionary contrasts cancer, muscle disease, deafness, and prehensive, new, and profound between humans and other organisms, blindness. Additionally, finding the understanding of complex living including those of life span, litter sizes, DNA sequences underlying such com- systems, with applications to inbreeding, and genetic drift. mon diseases as cardiovascular dis- human health, energy, global cli- ease, diabetes, arthritis, and cancers is mate change, and environmental Variations and Mutations being aided by the human variation cleanup, among others. [Denise Scientists have identified about 1.4 mil- maps (SNPs) generated Casey, HGMIS]à lion locations where single-base DNA dif- in the HGP in cooperation with the ferences (SNPs) occur in humans. This private sector. These genes and SNPs information promises to revolutionize provide focused targets the processes of finding chromosomal for the development of locations for disease-associated effective new therapies. Take a Genome Tour sequences and tracing human history. National Center for Biotechnology Informa- One of the greatest tion (NCBI) tutorial on how to use the publicly The ratio of germline (sperm or egg cell) impacts of having the available DNA sequence data and analysis tools: mutations is 2:1 in males vs females. sequence may well be in www.ncbi.nlm.nih.gov/Tour Researchers point to several reasons enabling an entirely new NCBI Human Genome Map Viewer: for the higher mutation rate in the approach to biological www.ncbi.nlm.nih.gov/cgi-bin/Entrez/hum_srch male germline, including the greater research. In the past, Guide to online information resources: number of cell divisions required for researchers studied one or www.ncbi.nlm.nih.gov/genome/guide/human sperm formation than for eggs. a few genes at a time. July 2001 Human Genome News 11(3–4) 5

In the News

Genomes: 15 Years Later We shall not cease from exploration And the end of all our exploring A Perspective by Charles DeLisi, HGP Pioneer Will be to arrive where we started And know the place for the first time. common ques- In a very real sense, much of biology —T. S. Eliot, “The Four Quartets, Ation asked by is about change. Reference genomes, Little Gidding” incredulous audi- along with various machine-learning ences 15 years ago algorithms developed and adapted was, “Whose during the genome project, also are toward the integrative systems physi- genome will you bringing microarray technologies to ology required to understand cell sequence?” After all, full power. In a few years, annotation behavior. High-throughput genomic there are several of the human genome will be com- methods, which are a revolution for billion human plete, and probes for every gene will global characterization, are a start in genomes, we were Charles DeLisi be arrayed on a solid phase substrate that direction. The long leap from reminded, all of of a few square centimeters. What characterizing to understanding, how- them different. microarray technology does better ever, will be possible only after analo- than any other current method is to gous technologies are developed for I often answered somewhat cryptically monitor and characterize change, proteins. that we would sequence everyone’s whether it is the result of normal cell and no one’s. We were after a refer- Although massively parallel technolo- growth and development, progression ence human genome—the organiza- gies for protein profiling are not yet toward disease, or response to exoge- tional and structural properties of the available, ideas are abundant and nous ligands. Diversity thus will be genome that are invariant across our fledgling methods are proliferating. In characterized with a precision and species. With this reference sequence the next 5 to 10 years we can expect breadth that may well revolutionize now in hand, we are in a position to the emergence of high-throughput medicine during the coming decades. return to the more subtle and complex technologies for profiling proteins in problem of diversity and to approach But, perhaps, an even more funda- various states of modification. Since it with a power that scarcely could mental change has begun. The many patterns of information process- have been imagined 15 years ago. high-throughput computational and ing, feedback control, memory, and experimental methods of the the like will be widely conserved Understanding diversity was in fact a post-HGP era are forcing molecular across species, bioinformatics tools— central motivation of the Human biology away from its spectacularly many yet to be developed—will amplify Genome Project from the start. I recall successful reductionist roots back what is revealed. The result will be a in 1985 Mark Bitensky, then Director à of Biological Sciences at Los Alamos National Laboratory, arguing passion- ately for genomic tools to characterize the molecular basis of disease predis- DeLisi Honored by President position and resistance and to develop harles DeLisi (Boston University), DOE Associate Director for Health an understanding that would make Cand Environmental Research in the mid-1980s, was one of 28 honorees possible individualized medicine— to whom President Bill Clinton presented the Presidential Citizens Medal what we now call pharmacogenomics. on January 8. According to the award citation, DeLisi was the first govern- Characterizing human polymorphisms ment scientist to conceive and outline the feasibility, goals, and parameters would require rapid and accurate of the Human Genome Project. He helped to galvanize an international technologies for differential sequenc- team of researchers to pool resources, create new technologies, and launch ing to detect that rare 1 in 1000 base the monumental task of gene mapping and sequencing. substitution that on average distin- At the presentation ceremony President Clinton added, “Charles DeLisi’s guishes different genomes. The imagination and determination helped to ignite the revolution in sequenc- required technology was not available ing that would ultimately unravel the code of human life itself. Thanks to in 1985, but today mass spectrometry his vision and leadership, in the year 2000 we announced the complete techniques can be used to perform sequencing of the human genome. Researchers are now closer than ever to 250,000 assays a day for single base finding therapies and cures for ailments once thought untreatable.” substitutions at an error rate of less than one part in 10,000, thus provid- Established in 1969 by Executive Order 11494, the medal is awarded at ing the gold standard for single nucle- the president’s sole discretion to U.S. citizens (living or dead) who have otide polymorphism verification. We performed exemplary deeds of service for the nation or for their fellow citi- now are beginning to assemble the zens. The 2001 award winners were recognized for their remarkable ser- database required for the arduous vice and accomplishments in a variety of areas, including civil rights, task of associating complex disorders medicine and health, sports, human rights, religion, education, disability with sets of common alleles (that is, advocacy, government service, journalism, and the environment. They different versions of the same gene). include Hank Aaron, Muhammad Ali, Elizabeth Taylor, Ronald Brown, Archibald Cox, Robert Rubin, Warren Rudman, and Charles Ruff.à 6 Human Genome News 11(3–4) July 2001

In the News very rapid increase in the rate of path- relatively small. The best estimate, determined computationally. The way and network discovery, classifica- based on rigorous statistical sampling ability to obtain virtually any struc- tion, and correlation with cell theory, is about 1300 for water-soluble ture at will opens the way to behavior. We thus will begin to build a domains. The same calculation indi- cell-system design, pathway modifi- deep understanding of the molecular cates that, with an increase of 20% a cation, and selection by directed correlates of change, of the differences year in protein-structure determina- mutations in proteins. and similarities between cells, and of tion, 95% of all such folds can be deter- Although humans took center stage the differences between identical cells mined in the next 15 years, even if we in the genome project, every scien- under varying chemical and physical continue to select sequences at ran- tist recognized the universality of conditions. These will include some dom. That’s a generous estimate on the methods. In particular, their largely overlooked conditions such as time because, by using the right type potential applicability to DOE’s envi- stress imposed by mechanical forces of information, we can readily choose ronmental programs was of great and the constraints of geometry. sequences in a way that increases the interest from the outset. odds of finding a new fold. The second At the heart of biological processes, reason for optimism has to do with Indeed, the new DOE plan, Genomes whether thermodynamically or kineti- advances in algorithms for structure to Life, reminds us that microbes are cally driven, is molecular structure. determination and, more important, “. . . the largest reservoir of . . . The ability is well within reach to the development of accurate and rap- diversity on the planet.” Specify an determine the structure of almost any idly evaluatable free-energy functions environmental condition, whether in protein domain computationally—and that include solvation. a deep sea vent where temperatures therefore rapidly and inexpensively. hover above 100°C or in a waste site A fold provides only a first approxima- where radiation levels greatly There are two reasons for such opti- tion to geometry, but, with the fold in exceed lethal human doses, and mism. First, the number of folds is hand, the detailed structure can be there will be found an ecological niche with microbial communities that have learned to accommodate and flourish. Among the most impor- New Institute at NIH tant challenges of post-HGP biology will be characterizing, understand- n April 20, the Secretary of the U.S. Department of Health and Human ing, preserving, and exploiting life’s Services approved the establishment of the National Institute of Biomedi- O robustness. cal Imaging and Bioengineering (NIBIB) and, at the same time, the Office of Bioengineering, Bioimaging, and Bioinformatics (called OB3) was abolished. As experimental methods become NIH is now proceeding with the selection of a NIBIB staff, director, and advi- increasingly powerful, the mathemat- sory council; and a Web site will be in place before the end of 2001. ical and computational methods of systems engineering will be essential Meeting Summary, Slides Available for converting data to knowledge, and A summary of the March 23 Bioengineering Research Partnership Grantee yet another discipline will be drawn Meeting can be downloaded from the Web (grants.nih.gov/grants/becon/ into the biological sciences. The dex- brpannualmeet2001.pdf). Slides from meeting presentations are at terity with which the computer sci- grants.nih.gov/grants/becon/brppresentations/.à ence community responded to the genomic challenge and the increasing acceptance of computation in the bench ¶ NSF Quantitative Systems Biology Report scientist’s tool kit constitute one of the most extraordinary developments The report of the National Science Foundation Workshop on Quantitative in the recent sociology of science. Systems Biotechnology (QSB), held in September 2000, is on the Web These trends no doubt will continue (www.wtec.org/qsb). QSB is defined as engineering research to augment the and become more pervasive as the prediction of a living organism’s phenotypic behavior from genomic infor- abstractions underlying life processes mation and environmental conditions. Workshop objectives were to suggest are revealed and data generation con- the scope of a new QSB program solicitation and to examine the possibility tinues to accelerate. The recently of conducting an international study in this area.à added Centers of Excellence in Bio- medical Computing at the National ¶ Booklet on Structural Biology Basics Institutes of Health and similar programs at the National Science Founda- The Structures of Life, a new 60-page, full-color booklet from the NIH tion and DOE are excellent initial steps National Institute of General Medical Sciences, explains how structural in preparing for the future of a science biology provides insight into health and disease and is useful in creating whose culture is changing almost as new medications. Geared toward an advanced high-school or early col- rapidly as the science itself.à lege-level audience, the booklet also features “Student Snapshots” designed to inspire young people to consider careers in biomedical research (order through www.nigms.nih.gov/news/publist.html). à July 2001 Human Genome News 11(3–4) 7

In the News International Group Coordinates Structural Genomics Efforts Shapes of Biomolecules Offer Clues to Their Function

s the human genome sequence available in all countries soon after scheduled for October 2002 in Anears completion, new projects their determination. In addition, the Berlin. The executive committee con- are under way to determine the 3-D agreement recognized the potential sists of Thomas Terwilliger (Los shapes of all proteins and other for collaboration among researchers Alamos National Laboratory), Udo important biomolecules encoded by in academia and industry. Heinemann (Max-Delbrück-Center the human genome and those of key for Molecular Medicine, Berlin), and The group elected an executive com- model organisms. The goals of inves- Shigeyuki Yokoyama (RIKEN mittee to establish an international tigators in the international struc- Genomic Sciences Center, Yokohama, organization for structural genomics tural genomics community are to Japan). à and to plan the next meeting, discover, analyze, and disseminate 3-D shapes of protein, RNA, and other biological macromolecules rep- resenting the range of nature’s struc- Imaging Biological Structures tural diversity. Currently, there is significant funding for such research Because molecular shape often provides clues to function in biological sys- in the United States, Canada, Euro- tems, obtaining a detailed knowledge of structure can help elucidate the pean Union, Israel, China, and basic principles of cell and organism function and the role of faulty struc- Japan. tures in disease. A broad collection of structural data will provide valuable information beyond that available from individual structures and will Airlie Meeting, Agreement have applications in the life sciences, biotechnology, and medicine. In April, a group of some 150 people Key advances making structural genomics research possible include the from 4 continents met at Airlie Center availability of synchrotrons and high-field NMR (nuclear magnetic reso- near Washington, D.C., to discuss the nance) instruments; the MAD (multiwavelength anomalous diffraction) general principles and coordination of method of phase determination; high-throughput cloning and recombinant research in structural genomics expression; a flood of information from genome sequencing projects; and (www.nigms.nih.gov/news/meetings/ bioinformatics methods for protein-fold assignment, model building, and airlie.html). The meeting was spon- function prediction.à sored by the NIH National Institute of General Medical Sciences, Insti- tute of Physical and Chemical Biologists Driving Synchrotron Use Rate Research (called RIKEN) in Japan, Life scientists (some 2400 of 6000) accounted for 40% of the users of the and U.K.’s Wellcome Trust. The four DOE synchrotron light sources in 2000, according to DOE Associate resulting “Airlie Agreement” builds Director for Biological and Environmental Research Ari Patrinos. Because on one produced at the first such of this demand, as many as 15 new synchrotron stations for protein crys- meeting held at the Wellcome Trust a tallography are expected to open in the United States alone by 2003, and year before (www.nigms.nih.gov/ more stations are under consideration. If half the protein crystallography news/meetings/hinxton.html). stations were devoted to high-throughput structure determination, The Airlie group reached general Patrinos estimated, 30,000 such structures could be generated each year. agreement on collaboration in a num- [Genome Technology, 21 (May 1, 2001).]à ber of areas, including standards for early data release, criteria for assess- ing the quality of structures, sharing of targeted protein lists, and archiv- ing and curating data. Human Proteome Organisation Formed Specifically, the “Airlie Agreement” provides for open sharing of scientific n June 25, the recently launched Human Proteome Organisation (HUPO) data and technological expertise. The Oannounced the election of Sam Hanash (University of Michigan) as its consensus conditions for data sharing Inaugural President (www.hupo.org). Proteomics is the high-throughput reflect the balance between two dif- study of protein expression and function. HUPO’s goals are to increase aware- ferent goals—timely and unrestricted ness of the Human Proteome Project (HPP) and the importance of proteomics release of all data and consideration in the diagnosis, prognosis, and therapy of disease; foster international cooper- for intellectual-property regulations ation; and promote scientific research. HUPO’s inaugural meeting, sponsored that vary significantly in different by Cambridge Healthtech Institute (CHI), was held in April in Virginia countries. For projects with public (www.healthtech.com/2001/hpr/), where topics included HPP, HUPO goals and funding, all data on biomolecular objectives, and nominations for the first president. CHI is planning the next shapes are to be made freely meeting for January 2002 in San Diego.à