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 family 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 representing 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 8 Human Genome News 11(3–4) July 2001

Comparative Genomics

Model Organism Sequence and Function Studies Flourish odel organism genomes sequenced in the Human Genome Project (HGP) have helped researchers iden- Mtify many functionally important human DNA regions, including genes, and further studies will help elucidate fundamental biological processes common to all species. These organisms include the mouse, fruit fly, yeast, the bacterium Escherichia coli, and the roundworm. Outside the HGP, vast amounts of genomic data are being generated for a variety of microbial, animal, and plant systems. In this section are articles on the flowering plant Arabidopsis thaliana and the pufferfish Fugu rubripes, followed by those on the laboratory mouse and an algorithm for comparisons of model organisms.à

New Genome Project Tackles Sushi Delicacy

cientists searching human genome comprises only about 400 million Sdata for genes and the DNA bases as compared with the 3.2 billion sequences that control their activity bases that make up human DNA. soon will have a valuable new resource, With far less noncoding (sometimes courtesy of the Japanese delicacy known as “junk”) DNA to sort known as Fugu (Fugu rubripes) or through, identifying biologically pufferfish. An international consortium, important regions in the Fugu led by researchers at the DOE Joint genome should be a much easier task. Genome Institute (JGI), has announced Comparing such DNA sequences from Black-Spotted Pufferfish. Photo by a collaborative agreement to sequence different species is an effective method Jeff Jeffords, http://divegallery.com the Fugu genome (www.jgi.doe.gov/ because evolution tends to conserve programs/fugu.htm). these regions. Although the Fugu genome contains JGI is generating draft sequences for Jazz, a new sequence assembler writ- essentially the same genes and regu- the Fugu genome project and applying ten at JGI. latory sequences as the human, it Sequence finishing and computational annotation are being done with In the News other consortium members: U.K. Human Genome Mapping Project Role of Key Breast Cancer Gene Identified (www.hgmp.mrc.ac.uk); Institute of esearchers Genevieve Nonet, Martha Stampfer, and Paul Yaswen at Molecular and Cell Biology, Singapore RLawrence Berkeley National Laboratory and Joe Gray, Koei Chin, and (www.imcb.nus.edu.sg); Molecular Colin Collins at the University of California, San Francisco, published an Sciences Institute, Berkeley article focusing on the functional characterization of the gene ZNF217 in (www.molsci.org/welcome.shtml); and the February 15th issue of Cancer Research 61. The gene is located in a Institute for Systems Biology, Seattle region of chromosome 20 found to have an increased copy number in many (www.systemsbiology.org). tumors, including 40% of breast cancer cell lines. Reintroduction of the ZNF217 gene into normal human breast cells in culture enables the cells to Pufferfish are raised in bulk on farms grow past the point at which they would normally stop. In addition to in Japan, where the taste is consid- becoming immortal, the epithelial cells containing ZNF217 gain several ered addictive. If prepared improp- other features characteristic of tumor cells, such as the ability to express erly, however, the flesh can be lethal telomerase. These results support the hypothesis that ZNF217 plays a role due to a highly potent neurotoxin in breast cancer by allowing the cells to continue growing and accumulat- present in Fugu ovaries, intestines, ing other changes necessary for malignant progression. à and livers. Eating pufferfish claims the lives of about 70 to 100 adventure- some (or unsuspecting) diners each Breast Cancer Researchers Use Gene Expressions year, most in rural areas and from sing gene-expression profiling, an international group of researchers led fish improperly cleaned at home. It is Uby Jeffrey Trent (NIH National Human Genome Research Institute) has the only food forbidden to be served made it possible to distinguish between hereditary and sporadic breast to Japan’s royal family. tumors for the first time. Simultaneous microarray assessments of some Fugu’s deadly effects have caught 6000 genes within breast cancer cells revealed clear and unique differences the imagination of many authors, in activity patterns, leading to a new test that shows exactly which genes including Ian Fleming. Near the end are active in a tumor cell. This capability may have important implications of From Russia with Love, the fic- for both diagnosis and treatment. The findings were published in the New tional James Bond is almost killed England Journal of Medicine 344(8), 539–48 (February 22, 2001). à by Fugu toxin.à July 2001 Human Genome News 11(3–4) 9

Comparative Genomics Plant Genome Significant to Agriculture, Energy, Human Health

or the first time, scientists have The complete sequence of Arabidopsis Fsequenced the complete genetic is directly relevant to human biologi- material of a plant, that of the mus- cal functions as well, because many tard weed Arabidopsis thaliana. The fundamental life processes at the international Arabidopsis Genome Ini- molecular and cellular levels are com- tiative (AGI) consortium published mon to all higher organisms. Some of the results and early analyses in the those processes are easier to study in December 14, 2000, issue of Nature, Arabidopsis than in human or animal Arabidopsis thaliana Source: National Science Foundation and articles are freely available on the models. Arabidopsis contains numer- Web through Nature’s Genome Gate- ous genes similar to those that prompt way (www.nature.com/genomics/ human diseases ranging from cancer with known functions. Strategies will papers/a_thaliana.html). and premature aging to ailments involve inactivating or over expressing such as Wilson’s disease, in which the each gene, one at a time, and observing Scientists expect that systematic stud- human body’s inability to excrete cop- the consequences. The NSF 2010 Proj- ies will illuminate numerous features per can be fatal. ect is part of a worldwide Arabidopsis of plant biology, including those of sig- functional genomics effort that will be nificant value to agriculture, energy, Gene Function Project coordinated in a manner similar to the environment, and human health. To help researchers capitalize on the Arabidopsis genome sequencing project. AGI, a collaboration of research groups genome sequence, NSF has begun the in the United States, Europe, and “2010 Project” to study the function of Data Japan, is funded by government agen- 26,000 Arabidopsis genes over the next For news, data, an interactive cies on three continents. U.S. research decade. Thus far, scientists have MapViewer, analysis tools, laboratory was supported in large part by DOE’s determined experimentally the roles protocols, and useful links, see The Office of Basic Energy Sciences, the of only about 1000, with another Arabidopsis Information Resource U.S. Department of Agriculture, and 14,000 estimated using computational (TAIR, www.arabidopsis.org). [Denise the National Science Foundation (NSF). methods to identify similarities of genes Casey, HGMIS]à Related to broccoli and cauliflower, Arabidopsis has emerged as a power- Drosophila Researchers Win Prize ful tool in plant molecular biology because of its rapid life cycle, small t its annual meeting in San Francisco on February 17, the American Asso- physical size, and relatively small Aciation for the Advancement of Science presented the prestigious Newcomb genome (125 Mb). The genome is orga- Cleveland Prize to five researchers representing the teams that completed the nized into 5 chromosomes containing sequence of the fruit fly. Gerald Rubin and Susan Celniker accepted the prize on some 26,000 genes. Genes are compact behalf of the Berkeley Drosophila Genome Project (BDGP), and J. Craig Venter, and closely spaced (about 4.6 kb apart), Gene Myers, and Mark Adams represented Celera Genomics. BDGP is a suggesting short regulatory regions partnership among Lawrence Berkeley National Laboratory; the University compared with animal genomes. of California, Berkeley; and Baylor College of Medicine. Potential Applications The 2000 prize, which recognized an outstanding paper published in Science between June 1, 1991, and May 31, 2000, was awarded for “The Genome Having the entire genome will help Sequence of Drosophila melanogaster.” The paper is a series of articles jointly researchers identify plant-specific authored by hundreds of scientists, technicians, and students from 20 public and gene functions and develop rapid, sys- private institutions in 5 countries. It appeared in the March 24, 2000, special tematic ways to locate genes impor- issue (www.sciencemag.org/content/vol287/issue5461). tant for growing larger crops that are Celera and BDGP began a collaboration in 1998 to determine whether the more resistant to disease and weather whole-genome shotgun-sequencing method pioneered by Venter could be used on and produce useful chemicals more organisms having many thousands of genes encoded in millions of DNA base efficiently. Plants also hold great pairs. The technique, previously tested successfully in much smaller bacterial potential as sources of renewable genomes, proved in the larger fruit fly genome to be faster and more efficient à energy, although they currently repre- than traditional methods. sent just 3% of U.S. energy resources. Completion of the Arabidopsis genome Microbial Conference Set for Tennessee sequence is revealing new information on how photosynthesis converts solar he Ninth International Conference on Microbial Genomes will be held Octo- energy and carbon dioxide into biomass, Tber 28–November 1 in Gatlinburg, Tennessee (www.esd.ornl.gov/microbial_ helping scientists develop better genomes). Hosted by Jizhong Zhou and Oak Ridge National Laboratory, the plants for fuel and chemical uses. meeting will focus on DNA sequence, sequence comparison analysis, and recent advances in functional genomics. [Contact: Web site, [email protected], or [email protected]] à 10 Human Genome News 11(3–4) July 2001

Comparative Genomics ORNL Mouse Program Provides Powerful Tools for Studying Human Genes Connecting Sequence and Function equencing genomes was the easy Human Disease Models Spart. Some major challenges facing Two allelic mutations were recently the new era of post-sequencing biology discovered that serve as models for include finding all genes and deducing human acute and chronic tyrosinemia their functions, elucidating the con- (Aponte et al., Proc. Nat. Acad. Sci. nections between mutations and dis- USA 98, 641–45, 2001). The group Dabney Johnson and friend. ease, and untangling the complex also has identified a significant candi- Source: ORNL networks of interactions controlling all date gene for an obesity-associated these processes in living systems. quantitative trait locus that may have by N-ethyl-N-nitrosourea and Model organisms such as the mouse, an imprinted or maternal-effect com- cryopreserving both tissues and whose genes and DNA regulatory ponent (Dhar et al., Physiol. Genomics gametes. DNA or RNA from these regions are remarkably similar to 4, 93–100, 2000). mice can be used to screen for point those of humans, provide powerful mutations in any gene. The muta- tools for illuminating our own genetic MGG is evaluating specific candidate tions are identified by high-through- material. genes for induced mutations leading put heteroduplex analysis followed to (1) abnormal hematopoiesis (pro- by DNA sequencing of PCR products Researchers in the Mouse Genetics duction of red blood cells), iron trans- from this large bank. Stocks of mice and Genomics (MGG) section at Oak port, and skeletal development; (2) carrying the specific gene mutation Ridge National Laboratory (ORNL) abnormal brain function, resulting in can be reconstituted from the frozen are using mouse genetics and muta- epilepsy; (3) defective kidney function, gametes. An allelic series of mouse genesis strategies to annotate biologi- resulting in juvenile death; (4) mutations for any preselected gene cally important features of the DNA perinatal death, possibly due to skull then can be used to test specific sequence and to provide functional or brain abnormalities; (5) early hypotheses about the structure- information for parts of the genome embryonic death due to a failure of function relationships of the gene that are expressed or that regulate yolk-sac hematopoiesis; (6) defective product in the context of a specific gene expression (http://bio.lsd.ornl.gov/ skin function, leading to alopecia and genetic network or environmental mgd). A complementary effort exploits increased risk of skin cancer; and (7) response. Initial targets for this type genome data for a better understanding modification of the agouti signaling of analysis will include DNA-repair of normal and abnormal biological proc- pathway involved in pigmentation, and other types of radiation- and esses defined by genetic and phenotypic obesity, diabetes, and cancer. stress-response genes; intracellular- analyses of mouse mutations. Screening Libraries transport genes; regulatory regions of selected genes, including imprinted Mouse Mutations High-throughput mutation scanning MGG is screening about 10% of the ones; signaling molecules; and cancer- is central to these gene-discovery susceptibility genes. mouse genome for chemically induced efforts, so MGG is producing a large recessive mutations affecting a wide bank of 3000 to 5000 inbred User Facility variety of physiological, neurological, C57BL/6JRn mice. They will carry The Mouse Genetics Research Facility behavioral, morphological, develop- point mutations induced in their sires is a DOE Biological and Environmen- mental, reproductive, cancer, aging, tal Research User Facility, offering and other genetic phenotypes (http:// expertise in mouse genetics and muta- bio.lsd.ornl.gov/mgd/mutagenesis/ MicroCAT Scanner Used for Screening genesis, molecular biology, and func- mutagenesis.htmlx). This activity tional genomics. Mutant mouse stocks, expands on previous studies that iden- A high-resolution X-ray–computed mutagenesis and phenotyping proto- tified over 50 mutations associated tomography (CT) system developed at cols, and genomic expression and with visible or lethal phenotypes in 1% ORNL by Mike Paulus and Shaun phenotype data are available to the of this genome. The group is integrating Gleason provides researchers with a high-throughput method of internally functional genomics and wider bio- microarray and proteomics technologies logical research communities through into these and other mutagenesis screening mice for defects and dam- age resulting from mutations. The database, cryopreservation, and crosses for a molecular-based set of MicroCAT scanner, which generates mouse-distribution efforts at ORNL. assays to complement whole-organism 3-D images in 7 to 20 minutes, elimi- The Mutant Mouse Database pro- phenotypic screening. Point-mutation nates the need to sacrifice and dissect vides searchable, one-stop shopping maps describing single-base changes the mice. This allows researchers to for new and archived mutant-mouse of the target mutagenized regions are monitor ongoing changes in animals, thereby facilitating studies on disease stocks created over the program’s being merged with DNA sequence 50-year existence. [Dabney Johnson, maps to correlate mutant phenotypes progression, consequences of aging, and responses to therapies. ORNL, [email protected], with specific genes. http://bio.lsd.ornl.gov/mgd] à July 2001 Human Genome News 11(3–4) 11

Comparative Genomics Consortium Achieves Draft Mouse Sequence

n May the international Mouse 85% to 90% of gene sequences are directly into the genomes of mouse ISequencing Consortium (MSC) similar in mouse and human, with embryos. Many will develop into mice announced the completion of a draft similarities ranging from 60% to 90%. that show symptoms similar to those map (3× coverage) representing at of affected humans, thus facilitating In addition to highlighting gene least 95% of the mouse DNA sequence. studies and the development of new sequences, mouse-human DNA compar- MSC plans to use longer DNA therapies. isons will help identify other regions stretches of known map position and responsible for turning gene expres- The new mouse data already have assemble the sequence fragments into sion on and off. Genome comparisons been used to locate the mouse equiva- a finished, highly accurate form. The also will provide insights into the evo- lent of a human gene that may be mouse is an invaluable resource for lutionary mechanisms underlying related to schizophrenia. The discov- interpreting human genome data and overall gene organization. ery may help researchers develop a finding human genes and other func- mouse model to study further the tionally important DNA regions con- Like all mammals, humans and mice gene’s association with this devastat- served by evolution. share the same physiological systems ing mental disorder. à and develop many of the same dis- “The success of MSC and other public- eases. Because of its private research consortia no doubt will small size, high fer- lead to future cooperative efforts to tility rate, and ease solve big problems quickly, especially * NCBI Mouse Resources of manipulation, the when the resulting data belong in the laboratory mouse Raw MSC data are freely available in the National public domain,” said Arthur Holden, offers great promise Center for Biotechnology Information Trace Archive cochairman of MSC. Comprising three (www.ncbi.nlm.nih.gov/Traces/trace.cgi) and in the in the study of the private companies and six NIH insti- Ensembl Trace Server (http://trace.ensembl.org). The genetic bases of dis- tutes, MSC was formed in October 2000. private company Celera Genomics also has generated ease susceptibility, a draft mouse genome sequence, which is accessible At 3 billion bases, the mouse genome development, and by subscription (www.celera.com). is comparable in size to that of humans. progress. Biotechno- The NCBI Mouse Genome Resources page (www.ncbi. Even more important, almost every logical methods now nlm.nih.gov/genome/guide/M_musculus.html) includes human gene appears to have a coun- allow DNA sequences the Graphical Mouse Genome Map Viewer for search- terpart in the mouse; among 4000 containing gene ing data by map position, gene symbol, gene name, or genes studied, fewer than 10 are pres- mutations associated marker name; Human-Mouse Homology Map; and ent in only one of the two species. with human diseases special BLAST form to facilitate searches of finished Researchers expect to find that about to be introduced mouse genome sequence.

Human-Mouse Comparisons Identify Candidate Sequences

A more detailed version of this article 19 (HSA19) nearly a year ago. Since human) and nonconserved features appeared in Science on July 6. then a DOE Joint Genome Institute distributed across the chromosome. (JGI) team headed by Lisa Stubbs at Comparison of related mouse and ess than 5% of the 3.2 billion bases LLNL has focused on functionally anno- HSA19 DNA identified more than in the human genome sequence is tating this chromosome, beginning with L 12,000 conserved sequence elements, thought to be occupied by genes, regu- an effort to identify and delineate all including candidate undiscovered latory elements controlling gene functional components of resident human exons (protein-coding gene expression, and other DNA regions genes. that serve important known biological fragments) as well as whole novel genes functions. One of the most efficient Spanning some 65 to 70 million bases and an estimated 4000 candidate reg- ways to identify these rare sequence and containing an estimated 1100 ulatory DNA sequences. Analyses features is to compare human DNA genes, HSA19 is one of the smallest, showed that highly conserved versions sequence with that of a related but yet most gene-dense, of the 24 human of virtually all single-copy human divergent species such as the mouse. chromosomes. To provide a tool for genes are found in mouse DNA and The power of the mouse model in functional annotation and evolutionary that mouse and human genes are studying human disease and in dissect- studies, the JGI-LLNL group isolated organized in very similar ways. and sequenced sets of overlapping ing gene function adds an important However, Stubbs and her team also BAC clones spanning mouse DNA dimension to such comparisons. noted striking species-specific differ- sequences related to HSA19. The draft ences in the content and functional A clone-based physical map assembled sequence’s high quality and solid capacity of certain types of genes, by scientists at Lawrence Livermore anchorage between human sequence including those encoding zinc-finger National Laboratory (LLNL) provided and related mouse clones enabled an transcription factors, olfactory the framework for completing the unusually comprehensive view of the draft sequence of human chromosome conserved (common to both mouse and (see Comparisons, p. 12) 12 Human Genome News 11(3–4) July 2001

Comparative Genomics

Comparisons (from p. 11) VISTA Software Widens Comparative View ith the increasing availability of cVISTA (complementary VISTA) is receptors, pheromone receptors, Whuman and mouse genomic used to look at differences between cytochrome P450, serine proteases, and sequence, a challenge confronting biol- such recently evolved species as mice many other types of proteins. These ogists is how to convert these large and rats or humans and chimpan- types of genes, which often are found amounts of data into useful biology. One zees. rVISTA (regulatory VISTA) organized into tandem clusters of 5 to of the more powerful algorithms for iden- combines a search of the transcrip- more than 60, are present in different tifying functional regions in genomic tion-factor binding-sites database numbers and types in mouse and DNA, including both genes and sur- with comparative sequence analysis, human DNA. This reflects the very rounding regulatory elements, involves thus greatly reducing the number of active duplication, divergence, and comparative sequence analysis. predicted binding sites and suggest- either functional or total loss of genes ing plausible hypotheses for further since separation of rodent and primate Confronted by a scarcity of tools for such studies, investigators led by Inna biological studies. Used extensively lineages. Stubbs and her colleagues esti- in LBNL’s Genome Sciences Depart- mate that these changes have given rise Dubchak and Edward Rubin in the Genome Sciences Department at Law- ment, VISTA also has become the to at least 100 actively expressed genes main comparative sequence analysis that are unique to either humans or rence Berkeley National Laboratory (LBNL) have developed a suite of soft- tool of several large sequencing mice. These lineage-specific genes are centers. likely to have significant impacts on ware tools called VISTA (VISualization biology, defining at least some of the Tools for Alignment). Incorporating a Individuals can use VISTA by anony- major physiological, morphological, and novel global-alignment procedure and mously sending sequence data to the behavioral differences between rodents components for visualization and anal- Web site (www-gsd.lbl.gov/vista) or and primate species. ysis, VISTA enables large-scale com- requesting a stand-alone computer parisons between DNA sequences of program (free for academic institu- HSA19 is related to mouse DNA found two or more species. Its visual output tions; modest licensing fee for private in 15 conserved segments from differ- is clean and simple, allowing for easy industry). More than 250 investiga- ent portions of mouse chromosomes 7, identification of conserved regions. Simi- tors have used VISTA online since it 8, 9, 10, and 17. Because both human larity scores are displayed for the entire became available in July 2000, and and mouse sequences were derived sequence, thus helping in identification close to 150 copies of the program from precisely mapped clones, the JGI of shorter conserved regions or regions have been distributed in academic team could identify the boundaries or with gaps. institutions of 20 countries. [Edward “breakpoints” of these 15 homology seg- Rubin, LBNL, [email protected]] à ments and examine the sequence con- Various modifications of VISTA deal tent and structure of the chromosome- with particular biological problems. rearrangement sites. Repeated sequences including clustered gene family members, LINE1, retrovirus sequences, and MGI Release 2.7 Enhances Allelle Detail Searching local duplications were found at all breakpoint sites. Results of this study ouse Genome Informatics (MGI) of a spontaneous or genetically indicate that, throughout evolution, Mprovides integrated access to data engineered allele; “Molecular “illegitimate” recombination (i.e., recom- on the genetics, genomics, and biology Information” reference describing of the laboratory mouse (www.informa- bination of related DNA sequences at or identifying the molecular tics.jax.org). Release 2.7 incorporates nature of the mutation responsi- nonhomologous chromosomal sites) the following enhancements to the ble for a given phenotypic allele; between gene families and other dupli- “Allelle Detail” page. cated sequences has driven evolution- and “Synonym References” con- New query field for “Promoter taining an allele synonym). ary changes in chromosome structure. Notes” can be used to search for “Gene Expression in This Mutant” The JGI team is now extending these when and where a transgene is expressed. includes the number of assays, studies to comparisons of related regions with a link to a display on the in a nonmammalian vertebrate species, “Molecular Information” (previously “GXD Expression Summary” page the chicken. Together with JGI’s emerg- “Molecular Description”) section of all expression data assayed in ing sequence of the pufferfish and other may include mutations, ES cell line mice carrying the allele. The vertebrate genomes being sequenced by and strain, promoter, notes (molecu- “Allele Detail” page no longer dis- public efforts worldwide, these studies lar), and reference (molecular). plays the mode of inheritance if it will provide the basis for deeper evolu- References associated with a is not applicable. tionary and functional studies of the esti- phenotypic allele used experimen- Allele Query Form: www.informa- mated 1200 HSA19 genes. The resulting tally or included as a major part of a tics.jax.org/searches/allele_form.shtml data and resources will be used to iden- review article are added. The page Help document on Using the Allele tify all HSA19 genes and their regulatory also displays three other kinds of Query Form: www.informatics.jax. elements and pave the way for studies of references (“Original Reference” org/userdocs/allele_help.shtml à biological function in model organisms. reporting the creation or discovery [Lisa Stubbs, DOE JGI and LLNL] à July 2001 Human Genome News 11(3–4) 13

In the News Converting Energy to Medical Progress Although typically focused on only one part of DOE’s Biological and Environ- Some Highlights of BER-Funded Research mental Research (BER), Human Genome News will now include material in Nuclear Medicine from the Medical Sciences Division Brookhaven National Laboratory, New York (MSD), which shares the same mission. One of the world’s leading laboratories for the design, synthesis, and applica- MSD’s nuclear imaging has all but elim- tion of radiopharmaceuticals for such priorities as substance abuse, aging and inated the need for exploratory surgeries. degenerative diseases, and the biology of tumors. Following is a summary of MSD’s new Lawrence Berkeley National Laboratory, California booklet, Converting Energy to Medical Specialized instrument development to improve detection of prostate, breast, Progress (April 2001). The booklet is and other cancers for such priorities as SPECT imaging for brain studies of available from HGMIS and can be mental illness. New radiotracers to study aging, heart disease, and cancer. downloaded from the Web Oak Ridge National Laboratory, Tennessee (www.doemedicalsciences.org). Genesis of BER when ORNL made available a vast selection of radionuclides for nuclear medicine research. Studies of new radiopharmaceuticals’ potential for uclear medicine is an exciting diagnostic and therapeutic applications in cancer and coronary artery disease. Nfield in healthcare that provides important information for diagnos- Memorial Sloan-Kettering Cancer Center, New York ing, evaluating, and managing dis- Pioneering work in the use of “monoclonal antibodies” to treat cancer. Novel ways to produce a variety of radionuclides to treat lymphoma, leukemia, and ease. Virtually all hospitals, as well prostate cancer. as many clinics and doctors’ offices, conduct nuclear medicine tests and University of California, Los Angeles scans. About 13 million (35,000 a New ways to image the biology and genetics of several diseases, including cancer, diabetes, heart disease, Alzheimer’s disease, and Parkinson’s disease. Pio- day) such procedures are performed neers in PET and microPET, which allows scientists to watch cells at work in each year on patients in the United the living person or mouse. States (and many more in other Washington University, St. Louis, Missouri countries) in cardiology, oncology, Innovative use of radionuclides in medicine. Important contributions to PET. neurology, sports and internal medi- Development of new organic carrier molecules and a new class of PET radio- cine, thyroid disorders, surgery, gas- pharmaceuticals based on metal radionuclides and first hormone receptor agents. trointestinal ailments, pulmonary University of Michigan, Ann Arbor disorders, infection, and dementia. Research in the chemical design and synthesis of radiopharmaceuticals and Nearly every nuclear medicine scan or their implementation in PET and SPECT brain-chemistry studies. Development test used today was made possible by of computer science for nuclear medicine imaging systems. Insight into several research funded by BER and its pre- neurological disorders that affect movement, memory, aging, and dementia. decessor agencies on radiotracers, radiation-detection devices, gamma cameras, positron emission tomogra- abnormal biochemical (physiological) process of disease, and even the molec- phy (PET) and single-photon emission changes. With its unique ability to ular errors that cause disease. computed tomography (SPECT) scan- reveal biochemical processes, nuclear Radiotracers interact with such biological ners, and computer science. medicine provides crucial information processes as bone mineral turnover, about numerous diseases. Nuclear In managing DOE’s nuclear medicine potassium transport in heart muscle, or medicine procedures are different from research program, MSD pursues two glucose metabolism in various organs X rays, scans by computed tomography main areas of scientific investiga- or tumors. Highly sensitive scanners (called CT) and magnetic resonance tion—imaging systems and detect and process the energy signals, imaging (called MRI), and ultra- radiopharmaceuticals (radiotracers). after which computer programs recon- sound, all of which primarily visual- The aim is to develop beneficial appli- struct them into diagnostic images. ize structure and shape (anatomy). cations of nuclear technologies for PET and SPECT, for example, produce medical diagnosis and treatment of Nuclear medicine images are produced 3-D images that look like multiple slices many diseases. by low levels of energy emitted from through the body. medically useful radiotracers intro- Biological Imaging Imaging Gene Expression All human characteristics depend on a duced into a patient’s body. SPECT gives off gamma rays and PET emits BER scientists have successfully cre- galaxy of biochemical reactions that ated images of genetically altered organ occur many millions of times per min- positrons, another form of energy that converts to gamma rays. Radiotracers function in animals. Now, MSD has ini- ute within the cells and tissues of the tiated exploratory research to develop body. A deranged chemical process can are designed to provide insights about cause disease, resulting in other healthy, normal biology, the biological (see Imaging, p. 14) 14 Human Genome News 11(3–4) July 2001

In the News

Toxicogenomic strategies under National Center for Toxicogenomics development through NCT are based on microarrays containing he outpouring of human genome To develop the field of toxicogenomics thousands of messenger RNA Tdata and the development of and coordinate an international (mRNA) fragments, the intermedi- large-scale, rapid, efficient technolo- research effort, the NIH National ary products of active genes, to cre- gies to probe them have transformed Institute of Environmental Health ate “gene-expression profiles.” Using the field of toxicology and engendered Sciences (NIEHS) created the bioinformatics tools, researchers a new specialty—toxicogenomics. National Center for Toxicogenomics combine these data with those from Researchers in this new field study (NCT). NCT aims to promote protein-expression profiles to deter- gene response to environmental advances in toxicogenomics and mine how disease may be influenced stressors and toxicants and seek to catalyze their application to the pre- by environmental factors. NCT’s understand the role played in disease vention and amelioration of environ- goal is to combine these microarray- by gene-environment interactions. mentally related diseases (www.niehs. based strategies into a unified The use of DNA microarray and nih.gov/nct.org.htm). approach, together with the infor- proteomic techniques to assess The establishment of NCT was matics infrastructure necessary to changes in gene and protein expres- announced in December 2000 by understand it. sion is a rapidly growing research NIEHS Director Kenneth Olden and area that will have a large impact in Deputy Director Samuel Wilson. NCT many areas, including the environ- (see Toxicogenomics, p. 15) Director is Raymond Tennant, NIEHS. mental health sciences.

Imaging (from p. 13) new radiotracers based on messenger can identify new molecular targets for Future Impacts RNA for dynamic imaging of gene imaging the biological activity of dis- The nuclear medicine of tomorrow expression in animals in real time. ease. In time, drugs may be custom will depend on the discovery of BER researchers at Sloan-Kettering, made for individual patients based on radiopharmaceuticals that seek spe- for example, created iodine-124 FAIU, genetic “fingerprinting,” and nuclear cific molecular and genetic targets, a highly specific radiopharmaceutical medicine will play a crucial role in this the design of companion advanced that provides the first nuclear medi- pursuit. scanners for creating meaningful cine images showing the expression of PET imaging techniques developed at images, and the promise of new certain genes in tumors in a live Washington University, for example, radiopharmaceutical treatments for animal. à are helping to identify which patients cancers and genetic diseases. As scientists discover more informa- with breast cancer will respond to tion about the relationship between tamoxifen hormone therapy. Scien- genes and disease or behavior, they tists there also have developed fluo- rine-18 fluoroestradiol that targets estrogen receptors on breast tumors. The presence or absence of PET Developers Win abundant estrogen receptors in Kettering Prize breast cancer cells can help doctors select the most appropriate chemo- avid Kuhl (University of Michi- therapy for these patients. Dgan, Ann Arbor) and Michael Phelps (University of California, Since mice can be engineered biolog- Los Angeles, School of Medicine) ically to carry genes that produce are co-winners of the Charles F. disease, molecular probes such as Kettering Prize for their involvement microPET allow the imaging of dis- in the development of positron emis- ease initiation and progression in a Miniature PET sion tomography (PET). The living mouse. In concert with this scanner, the Kettering Prize, sponsored by the research, scientists are investigat- “microPET” for imaging mice, General Motors Cancer Research ing highly sophisticated drugs developed at Foundation, recognizes the most out- designed to correct the molecular the University standing recent contribution to the errors of disease. Combined with of California, diagnosis or treatment of cancer. the explosive growth of knowledge Los Angeles, Both researchers have long-standing from genome research, PET and with scan inset. BER research support involving PET microPET play a major role in the and its medical applications for diag- promising new era of molecular nosis and therapy.à diagnostics and therapeutics. July 2001 Human Genome News 11(3–4) 15

In the News Exploring the Impact of Genetics Research on Minorities

ne of the goals of the National Pictured left to OEducational Foundation of Zeta right: Kathryn Phi Beta Sorority, Inc., is to empha- Malvern (Zeta Phi size education in minority communi- Beta Sorority, Inc.), ties. In keeping with this goal, the Ari Patrinos (DOE Office of Biological foundation has planned and con- and Environmental ducted three major informational Research), Issie conferences on the challenges and Jenkins (Zeta Phi impacts of the Human Genome Project Beta Sorority, Inc.), (HGP) within the last 3 years: New and Daniel Drell Orleans in April 1999, Philadelphia (DOE Human in July 2000, and Atlanta in July. Fol- Genome Program). low-up meetings and training sessions all over the country have been carried out by members of the educational foundation. Following is a sum- The conference took place several concerns raised by HGP research, mary of the Philadelphia meeting, weeks after President Bill Clinton’s including ethical, legal, and social held July 7 and 8, 2000. announcement that a rough draft of issues (ELSI). The symposium also The 250 attendees included represen- the human genome sequence had addressed the need to expand the tatives of minority organizations, been completed and that differences pool of minority scientists and the civic and religious groups, health had been resolved between private challenge of interesting minority communities, government, student and public sectors in the sequencing students in science. groups, and the public. Because the race. Meeting objectives were to make conference was held in conjunction minority communities more aware of Conference Program with the sorority’s national meeting the HGP and its status, to inform The keynote speaker was DOE Associ- (July 9–14), minority representatives them of the project’s benefits, and to ate Director of Biological and Envi- from states across the country also provide a forum for minority input. ronmental Research Ari Patrinos. were present. Other topics were implications and He discussed the history and accomplishments of the HGP and provided background information on Clinton’s announcement. Indicating that the Toxicogenomics (from p. 14) HGP’s outcome will dramatically affect the country’s economy, Patrinos emphasized the importance of involv- This challenge exemplifies the ongoing making possible the early diagnosis ing minority communities so that all paradigm shift occurring across the of cellular responses and the preven- can share in project benefits and life sciences. Researchers are moving tion of or intervention in human related concerns can be avoided or toward monitoring cellular events on a disease. responsibly addressed. large-scale, global level that will facili- Other NCT goals are to increase tate a broader view of how living sys- Presenters included John Quackenbush understanding of the pathways tems respond to specific stresses, (The Institute for Genomic Research), involved in biological response to drugs, and toxicants. Data generated who spoke on “Decoding the Book of environmental stressors and how by such research will provide extraor- Life” and how genomics will influence these changes differ with genetic and dinarily detailed information on coor- approaches to a variety of problems dose differences; establish a publicly dination profiles for cellular networks in modern biology. The challenge for available relational database of of responding genes and proteins, help the future, he said, will be to identify toxicogenomics research; and pro- define important target molecules for specific genes, determine their func- mote collaborative research that will toxicity studies, and suggest future tions, and explore genetic changes combine toxicology and disease biomarkers and alternative testing that can lead to disease. pathology with gene-expression pro- procedures. filing, proteomics, and single-nucleo- Panels Experiments using such microarray tide polymorphism analysis using the A panel discussion on the project’s technologies also will help define com- Chemical Exposure in Biological Sys- implications for minority health plex regulatory circuitry within a cell, tems Data Base. A symposium on issues included Georgia Dunston and tissue, or organ that is responding to Gene Expression and Proteomics in Robert Murray (both at Howard Uni- specific stressors. Studies may help Environmental Health Research will versity Medical School). In address- pinpoint locations and time points for be held December 3–4 in Bethesda, ing recent programs that screen for effectively interceding in a cascade of Maryland. [James K. Selkirk, Deputy genetically determined health biochemical and molecular events Director NCT, 919/541-2548, influenced by environmental stressors, Fax: -1460, [email protected]]à p. 16 à 16 Human Genome News 11(3–4) July 2001

In the News disorders, Murray spoke of ethical and used to stigmatize or discriminate not included in the baseline tem- legal conflicts that can arise when the against minorities. plate, some might not be considered disorder will not be manifested for a by the big pharmaceutical compa- Dunston questioned the genetic sam- number of years and intervention is nies intent on making commercial ples being used in human genome unknown or of questionable value. He drugs linked to specific genotypes. research and whether they represent indicated that such problems often Jackson pointed out that minorities enough variation in populations. Indi- arise when a person is merely placed cannot assume inclusiveness at any cating that the genome study deals in a category of increased risk for stage of the HGP and that the pat- with the foundation of identity, she developing the condition; this situa- tern of sampling often reflects power expressed concern that current tion is more likely to have serious neg- relationships. Minorities may need research could be too limited. ative consequences for members of to demand such inclusiveness. minority groups. Finding a solution to Mary Kay Pelias (Louisiana State Daniel Drell (DOE Human Genome this dilemma is imperative before any University Medical School) spoke on Program) presented a review of the widespread genetic screening pro- genetic problems in clinical practice HGP and a recap of the first day’s grams are put in place, according to and biomedical research. Using hered- proceedings. Murray. He and Dunstan agreed that, itary traits and diseases as illustra- without protective measures, informa- tions, Pelias described how they are At the panel on HGP ELSI for tion from genetic screening could be manifested in Louisiana’s diverse pop- Minorities, facilitator Issie Jenkins ulation and how relevant historical (then foundation chair) raised the developments and patterns of immi- issue of confidentiality and uses of gration can influence health issues. individual genetic information; the potential for discrimination in Fatimah Jackson (University of Mary- healthcare, health insurance, and land) emphasized that consideration employment; the potential for use of the African-American perspective and misuse of genetic data in the on human genome research is critical, criminal justice system; and the ben- although it cannot be used as a substi- This newsletter is intended to facilitate communi- efits of minority participation in tute for those of other groups. Insights cation and collaboration, help prevent duplica- clinical trials. Jeroo Kotval (School tion of research effort, and inform persons of African Americans are important of Public Health, New York State interested in genome research. Views ex- because they so frequently have been pressed are not necessarily those of the Depart- University) spoke of ethical issues victims of “science” and “quasigenetic” ment of Energy Office of Biological and involved in a market-driven Environmental Research. Suggestions are in- inquiries. This group was among the healthcare system and identified the vited. first to call for representative sam- following four principles as central: Human Genome Management pling in the HGP, Jackson said, and Information System (HGMIS) just distribution and quality of for the inclusion of African-American Oak Ridge National Laboratory healthcare, cost-effective care, and 1060 Commerce Park, MS 6480 genetic sequences in the human trust. Each of these principles could Oak Ridge, TN 37830 genome’s template. If all groups were 865/576-6669, Fax: /574-9888 www.ornl.gov/hgmis Managing Editor Editors/Writers/ Betty K. Mansfield Designers [email protected] Anne E. Adamson Denise K. Casey ¶ Minorities and the Human Genome Project Production Assistants Judy M. Wyrick Marissa D. Mills The book Plain Talk About the Human Genome Project, edited by Edward Sheryl A. Martin Smith and Walter Sapp, is a compilation of talks presented during a 3-day Laura N. Yust conference at Tuskegee University in September 1996 [HGN 8(2), 9–10]. Dis- U.S. Department of Energy tinguished leaders, scientists, ethicists, educators, and students spoke on Office of Biological and wide-ranging topics related to the Human Genome Project’s promise and per- Environmental Research ils, matters of race and diversity, and education about the project and its Ari Patrinos, Associate Director www.science.doe.gov/ober/ober_top.html implications. 292 pp., 1997. [Ordering Information: http://agriculture.tusk. edu/Genome2/Plain_Talk_HGP/Plain_Talk.html] Life Sciences Division, OBER Marvin E. Frazier, Director The Human Genome Project and Minority Communities: Ethical, Social, and www.science.doe.gov/ober/lsd_top.html Political Dilemmas, edited by Raymond Zilinskas (Monterey Institute of Contact: Daniel W. Drell, 301/903-6488, International Studies) and Peter Balint (University of Maryland) addresses Fax: -8521 the divisions between minority groups and the scientific community, particu- [email protected] or larly in the area of medical and genetic research. The book consists largely of [email protected] talks by distinguished speakers at the conference, “The Human Genome Pro- Special thanks to Carolyn Krause, ORNL ject: Reaching the Minority Communities in Maryland,” held in June 1997 at the University of Maryland at Baltimore [HGN 9(1–2), 19–21)]. In an essay that was not part of the conference, the editors argue that, although minori- This newsletter is prepared at the request ties tend to be skeptical of medical research in general and genetics research of the DOE Office of Biological and Envi- in particular, the Human Genome Project has the potential to make dra- ronmental Research by the Life Sciences matic positive contributions to the health of all people. 144 pp., 2000. [Avail- Division at Oak Ridge National Labora- able through bookstores, including online suppliers.]à tory, which is managed by UT-Battelle, LLC, under contract AC05-00OR22725. July 2001 Human Genome News 11(3–4) 17

In the News be impacted by the new genetic tests pursue internships in science and conduct more research into minority and their implications. related fields. issues and concerns. Jenifer Smith (DNA Analysis Unit, Interest minority students in Leanne Washington (Pennsylvania FBI Laboratory) explained how law math and science courses in mid- House of Representatives member) enforcement officials use DNA evi- dle and high school; college is too was the closing luncheon speaker. dence and the Combined DNA Index late to begin. She spoke of state involvement and System (CODIS)—a collection of DNA of the important need for informa- databases from forensic laboratories Closing Session tion in minority communities. She around the United States. CODIS The closing session was conducted by committed to sponsoring a state-wide includes DNA profiles of individuals Kathryn Malvern (now foundation conference on the HGP. convicted of such serious crimes as chair) on “What Next?” for continued minority involvement in education The foundation received many favor- rapes and homicides. These profiles able comments on the informative are compared with those collected in about genomic research developments. Suggestions were made to conference. A number of participants other cases waiting to be solved. All expressed the desire to keep abreast states have legislation allowing the continue information sessions at or involving local churches, prepare and of developments and contribute to collection of DNA samples from con- policy and legislative decisions regard- victed offenders. Questions were disseminate conference proceedings and collaborate with other groups. ing genetic research and the use of raised about the use of such evidence genetic information. The proceedings with respect to minorities. Attendees also recommended dissem- of this meeting are on the Web Phyllis Epps (Health Law and Policy inating factual information written (www.ornl.gov/hgmis/publicat/ Center, University of Houston Law in layman’s terms at Black Expo and zetaphibeta/) [Issie L. Jenkins, Esq.] Center) spoke of recent advances in minority festivals and on videotapes. ______pharmacogenomics (drug targeting to Information in cartoon form should The conference was supported by DOE a patient’s genetic makeup) that have be developed for children. and NIH through the ELSI components of their respective human revealed drug-metabolism differences They also saw a need to form local linked to race, ethnicity, and gender. genome programs. The U.S. Equal HGP Awareness Teams to keep Employment Opportunity Commission, As a result, drug manufacturers, abreast of developments; provide eas- Philadelphia District Office, provided researchers, and physicians will have ily understood examples of the pro- assistance as a cooperating agency legitimate reasons to consider race in ject’s benefits; develop a Web site sponsor. Funding also was received from judging the effectiveness of medi- with short lists of benefits and posi- the March of Dimes and Merck cines. Given past history, patients will tive and negative potentials; and Research Laboratories.à regard race-based treatment with sus- picion, and the medical community will find it a great challenge to balance the benefits of different treatments against the risks inherent in classify- ing persons for whatever reason. Sandia, Celera, Compaq Work Workshops on Next-Generation Computing Three afternoon workshops led to a n January, Sandia National Labora- bringing together the capabilities of series of recommendations and con- Itories and Celera Genomics, Inc., three leaders in bioinformatics, cerns that included the following: signed a 4-year Cooperative Research high-performance computing, and Monitor the status of health insur- and Development Agreement to massively parallel systems. Using ance coverage for genetic testing begin work on the next generation of both public and private resources, and counseling, an important issue computer software and hardware for the multimillion-dollar arrangement for minority communities. computational biology and a full first was suggested by Sen. Pete V. range of applications in the life sci- Domenici (R-N.M.) and guided to Create more training opportunities ences. Under contract to Sandia, completion by Ari Patrinos, Associate for veteran teachers and encourage Compaq Computer Corporation will Director of the DOE Office of Biologi- mentors for minority students in design the new machine, which is cal and Environmental Research. such scientific developments as expected to achieve 100 trillion oper- genetics. J. Craig Venter, Celera’s president ations per second (100 TeraOps). By and chief scientific officer, said, “Just Develop career-day presentations sharing some computing technologies 3 years ago, the computational needs to increase minority student developed by Sandia, Celera and of biology were thought to be minor awareness of the large number and Compaq ultimately may reach the and irrelevant to the computing types of current and future opportu- “petacruncher” level (1000 TeraOps). industry. Today, biologists are setting nities in the genomic, biomedical, This level of cooperation is necessary the pace of development in the and biotechnology industries. to meet the dramatic demands of industry.” Encourage minority students to emerging genomics and proteomics volunteer, take part-time jobs, and applications at affordable prices by (see Computing, p. 18) 18 Human Genome News 11(3–4) July 2001

In the News

extra genetic material (plasmids) Scientists Decode Genes of Microbe that house genes conferring resis- that Thrives in Toxic Metals tance to the harmful effects of a wide array of heavy metals. Having the nderstanding the genetic makeup team, now are seeking to understand draft genome sequence will make Uof microbes that thrive in polluted and manipulate the sequence. The manipulation of these naturally environments may one day help scien- research was funded in part by DOE’s existing resistance factors more fea- tists engineer bacteria to clean con- Microbial Genome Program. sible. Scientists also are working on taminants from soil. In a step toward ways to limit the ability of bacteria This bacterium was first isolated in that goal, the DOE Joint Genome to spread genes inadvertently so Belgium in 1976 from settling-tank Institute has released the draft DNA they will stay in the bacteria where sludge that was polluted with high sequence of the toxin-tolerant Ralstonia they are put. This can be done by concentrations of heavy metals. Exam- metallidurans. Researchers at DOE’s crippling Ralstonia’s ability to trans- ination revealed that, in addition to its Brookhaven National Laboratory fer genes or by using host strains chromosomal genes, Ralstonia has (BNL), in collaboration with a Belgian that normally do not transfer genes. Potential future benefits include transferring Ralstonia’s heavy- metal resistance genes to microbes ¶ Microbial Genome Program Flyer Available with capabilities for breaking down A brochure on the DOE Microbial Genome Program is available in print other pollutants, thereby engineer- from HGMIS and can be downloaded from the Web site (www.ornl.gov/ ing strains with a combination of microbialgenomes/pubs.html). The text includes information on DOE’s useful traits. Another possible reasons for studying and sequencing microbes, possible microbial appli- application is to link Ralstonia’s cations, and related research and Web sites. All current and past DOE- heavy-metal uptake to genes that supported microbial projects are listed with details on their status and cause bacteria to glow, or biolumi- their potential usefulness. nesce, when indicating the presence of heavy metals in the soil. The * JGI Planning Another “Microbe Month” higher the concentration of metals, the brighter the glow. Because of the success of last year’s “Microbe Month,” DOE’s Joint “What we’re doing is building on the Genome Institute (JGI) in Walnut Creek, California, is planning another diversity of biology,” said BNL’s John such event for this fall. Last October, high-quality draft sequences of 15 Dunn. “Here’s a bacterium that bacterial genomes were produced—a rate of more than one genome for potentially could be used as a tool to every one and a half working days (www.jgi.doe.gov/tempweb/News/ help us clean up the environment news_11_2_00.html). In addition to their value in basic research, many and to monitor how well we’re microbes have immediate implications for the economy and the environ- accomplishing that goal.”à ment. Xylella fastidiosa, for example, is a pathogen carried by insects that infects grapevines; citrus and almond trees; oleander bushes, used as median strips on California highways; and other important plants. [More information: http://compbio.ornl.gov/channel]

* Educational Kit on the HGP Computing (from p. 17) The Human Genome Project and Patrinos noted, “The most fertile integrating system hardware and other sponsors have created a ground for scientific discovery lies at software and on optimizing multimedia kit as an educational the interface of disciplines, with the performance. tool for high school students and most important at the junction of the general public. The Human biology and information science.” The alliance will use Compaq Alpha Genome Project: Exploring our processors connected in a massively Molecular Selves includes a To accomplish the consortium’s goal parallel configuration with CD-ROM with seven varied seg- of creating a prototype by 2004, extremely high bandwidth and ments; The Secret of Our Lives,an Compaq and Sandia will collaborate low-latency mesh interconnects. award-winning video documen- on system hardware and software. Sandia currently operates the most tary; a commemorative wall Celera and Sandia will focus on powerful Linux-based supercom- poster; and Genetics, The Future of advanced algorithms and new visual- puter in existence and is home to Medicine, an informational bro- ization technologies for analyzing the ASCI Red, the first TeraOp super- chure. Request a free copy or use massive amounts of data generated computer, one of the fastest in the the kit online (www.nhgri.nih. by high-throughput machines. All world. à gov/educationkit). à three groups will contribute to July 2001 Human Genome News 11(3–4) 19

Resources

* HGMIS Notes HGP Handouts winners in chapter competitions were eligible for the international HGP Fact Sheet Published HGMIS will send multiple copies of contest. HGN and other genomics-related Updating articles drawn from the materials to relevant meetings on A HGMIS entry in the News and November 2000 issue of Human request and without charge (see con- Trade Articles category, “Genes, Genome News, the Human Genome tact, p. 16). Dreams, and Reality: The Promises Management Information System and Risks of the New Genetics” by (HGMIS) has published the 4-page Denise Casey, won a Merit Award Human Genome Project Fact Sheet HGMIS Documents, Web Site in Technical Publications. The arti- to provide quick and timely answers Win Awards cle appeared in the journal Judica- to frequently asked questions. ture 83(3) (www.ornl.gov/hgmis/ Topics include gene patenting, the The DOE Microbial Genome Program publicat/judicature). “rivalry” between public and private Report, produced by HGMIS, won a number of awards in the 2000–2001 STC, the largest organization of its sectors, HGP funding since 1987, type in the world, is dedicated to and challenges for the future. This competitions sponsored by the Soci- ety for Technical Communication advancing the arts and sciences of free document is available in bulk technical communication. Its for meetings and educational pur- (STC). HGMIS was initiated in 1989 by DOE to make information about 25,000 members include writers, poses (865/576-6669, mansfieldbk@ editors, illustrators, printers, pub- ornl.gov). the Human Genome Project accessible to many audiences. lishers, educators, students, engineers, and scientists employed in a HGMIS Requests Change In the STC East Tennessee Chapter variety of technological fields. of Address, Subscription (ETC) competition, the microbial report (www.ornl.gov/hgmis/publicat/ Web Awards Status microbial) received a Distinguished After each issue of HGN is printed (first place) Award in Online Commu- HGMIS also has received numer- and mailed, many copies are nications and two Merit (third place) ous awards for its Human Genome returned to HGMIS because the Awards, one in Technical Publica- Project Information Web site addressee has moved. Some sub- tions and the other in Technical Art. (www.ornl.gov/hgmis). Some recent scribers may wish to drop their print In addition, the document was judged ones are from Scientific American, subscriptions. Please use the back ETC’s Best of Show in Online Com- Schoolsnet, BigChalk, KidsHealth, page of any issue to notify HGMIS of munications and went on to receive CyberU, sciLINKs, Geniusfind, a change in address or subscription another Distinguished Award at the ISI, Hardin MD, Awesome Library, à status or to request information. international level. Only first place and ResPool Research Network.

Send article suggestions to Betty Mansfield ([email protected]).

* Genetic Testing, Counseling Resources GeneTests and GeneClinics, com- clinics; searchable by geography, specific hereditary diseases, as well panion resources on genetic counsel- population (age group), and as overviews on disease families. ing and testing for hereditary subspecialty, if applicable. GeneClinics contains about 80 dis- disorders, are freely available on the ease profiles and overviews. About Genetic Services: Primer of Web. In the past year, several new educational materials about genetics The two resources gradually are features and many disease profiles counseling and testing; useful for becoming more integrated, with have been added. consumers and nongeneticist links from GeneClinics profiles to GeneTests (www.genetests.org): healthcare providers. specific testing, counseling, and educational resources in GeneTests. Genetics Laboratory Directory: List Teaching Tools: Downloadable GeneTest search results link to rele- of about 500 U.S. and international PowerPoint slide presentation on vant GeneClinics profiles. laboratories that are testing for the availability and use of genetic some 820 diseases; searchable by a services; suitable for genetics profes- One-time registration is required for variety of parameters, including dis- sionals to teach nongenetics health- GeneTests (use the New Users but- ease name, gene name, affected care providers. ton on the Home Page to register organ system, and others. and select your passwords). [Con- GeneClinics (www.geneclinics.org) Genetics Clinic Directory: List of 950 tacts: [email protected] or Contains 113 expert-authored and U.S. genetics and prenatal diagnosis [email protected]] à peer-reviewed full-text articles on 20 Human Genome News 11(3–4) July 2001

Resources

Web Sites * U.K. Scholarships ¶ New Report Looks at Biotechnology Business Marshall Scholarships Small-Scale Solutions www.genomeweb.com Up to 40 scholarships for study Global Environmental Change: toward a degree in the United King- Microbial Contributions, Microbial News and information on the busi- dom are awarded yearly to U.S. citi- Solutions, a new report from the ness and technology of genomics and zens who hold a first degree with a American Society for Microbiology bioinformatics worldwide. minimum GPA of 3.7 after freshman (ASM), suggests that microbiology www.genengnews.com year. The scholarships pay full costs, can provide solutions to such seri- Information about all facets of the including travel and an allowance for ous environmental challenges as the biotechnology field worldwide from a dependent spouse. Candidates increase in greenhouse gases and Genetic Engineering News. must have received an undergradu- other stresses. Written by Gary M. www.bio.com/os/start/ ate degree in any discipline within 3 King (University of Maine), James years of taking up the scholarship, bioOnline site. Industry and research Tiedje (Michigan State University) which is tenable at any British uni- news, reports, education, career and the ASM Committee on Envi- versity for 2 to 3 academic years. center. ronmental Microbiology, the report Applications must be made through a makes four recommendations for www.signalsmag.com regional center in the United States enhancing microbiological solutions Online magazine of biotechnology and are due in mid-October of the to global change: industry analysis. year preceding tenure. Integrate an understanding of ELSI Marshall Sherfield Postdoctoral microbiological processes at all Fellowships organizational levels, from indi- www.humgen.umontreal.ca Two postdoctoral fellowships will be vidual organisms to ecosystems. Database on legal, social, and ethical awarded in 2002 for U.S. scientists Discover, characterize, and har- aspects of human genetics. Organized and engineers to undertake up to a ness the abilities of microbes that around a list of international year of research at British universi- play important roles in transfor- policymaking organizations and bibli- ties or research institutes. Fellow- mations of trace gases and vari- ographies of policy statements on ships cover full costs and allowances ous toxic elements. various topics.à for travel and accompanying spouse and children. Awardees are expected Implement policies that promote to engage in a meaningful collabora- effective long-term research on tion with a university or institute the microbiology of global change. ¶ Encyclopedia of Ethical, whose research is complementary to Establish programs to train peo- Legal, and Policy Issues their areas of expertise. Applications ple to solve tomorrow’s complex are due October 9. in Biotechnology environmental problems. More information about both programs In a comprehensive 2-volume, 1160-page The report can be downloaded is on the Web (www.acu.ac.uk/ reference work, the editorial team of (www.asmusa.org/pasrc/pdfs/ marshall).à Thomas Murray (The Hastings Center) globalwarming.pdf).à and Maxwell Mehlman (Case-Western Reserve’s Law-Medicine Center) bring together leading experts from a variety of fields to describe ethical, regulatory, ¶ Nature 2001 Yearbook and policy issues in biotechnology; analyze their implications; and pres- of Science and ent public policy options. Published Technology Next Wave Online late in 2000, the encyclopedia includes The Nature Yearbook of Science and Publication a chapter written by Daniel Drell of Technology 2001 provides a comprehen- the DOE Human Genome Program’s Next Wave, a weekly online publica- sive view of the major trends and Ethical, Legal, and Social Issues pro- tion from Science, covers scientific players in the fast-moving world of gram. This is the fourth and final training, career development, and science. It profiles thousands of insti- entry in the Wiley Biotechnology Ency- the science job market. It includes tutions and organizations in almost clopedias series. features, news items, career columns, every country in the world, including and perspectives in the job market, Visit the Web site for a detailed developing nations, and all U.S. career transitions, job hunting, description, table of contents, and a states. The reference work also diversity and work life, advice for sample article, “Human Enhancement includes specially commissioned arti- graduate students, science policy, Uses of Biotechnology,” by Robert cles and essays by leading experts in and postdoctoral and faculty issues. Wachbroit (www.wiley.com/products/ their fields. One volume, 2000 pp., Some articles are freely accessible, subject/reference/murray_index.html). 2001. [Orders: www.naturereference. and others require a modestly priced [Orders: Web site, 800/225-5945, or com/NatureYearbook/nature_ subscription (http://nextwave. [email protected]]à yearbookspecial.htm]à sciencemag.org).à July 2001 Human Genome News 11(3–4) 21

Resources

* Twisted Ladder Media In the News Issues Two CD-ROMs Winners of Postdoctoral Fellowships Announced Two new groundbreaking CD-ROMs ince 1995, the Sloan Foundation and DOE have jointly supported up to use innovative multimedia and easy Sten Postdoctoral Fellowships in Computational Molecular Biology each navigation techniques to make the year. The program, which has been renewed for another 3 years, is aimed at genomic revolution understandable catalyzing career transitions into computational molecular biology from and accessible to many audiences. physics, mathematics, computer science, chemistry, and related fields. See the Sloan Web site for many other funding opportunities The New Genetics: Courseware for (www.sloan.org/programs/scitech_fellowships.shtml). Physicians is designed for medical doctors who wish to update their Winners of the competition that closed in February are shown below with knowledge about genetics and their Ph.D. institution and field, postdoctoral institution, and sponsoring genomics. Price includes Continuing senior scientist. Medical Education (CME) credits from Stanford University. Joyce Duan (Baylor College of Medicine; Biochemistry): University of Cali- fornia, Los Angeles; David Eisenberg The New Genetics: Medicine and the Human Genome presents the same Hugh MacMillan (University of Colorado; Applied Mathematics): Univer- content, without CME credits, for col- sity of California, San Diego; Andrew McCammon lege students, researchers, nurses, Jay Storz (Duke University; Biology): University of Arizona; Michael Nachman policymakers, attorneys, and others who are interested in the impact of Justin Fay (University of Chicago; Population Genetics): University of Cali- genetics and genomics on healthcare fornia, Berkeley; Michael Eisen and society. Shayan Mukherjee (Massachusetts Institute of Technology; Computational Both CD-ROMs can be ordered Neuroscience): Whitehead Institute; Todd Golub through the Web site, which contains Duncan Odom (California Institute of Technology; Chemistry): Whitehead sample text, complete content outline, Institute; Richard Young feature demonstrations, and animations (www.twistedladdermedia.com). They were produced by Sara Tobin (Stanford University) and Ann Boughton (Twisted Ladder Media), with support from the Ethical, Legal, ANL’s Advanced Photon Source Illuminates and Social Issues component of DOE’s Ribosomal Activities Human Genome Program. à sing the Advanced Photon Source Ramakrishnan stated that pharma- Uat Argonne National Laboratory ceutical and biotechnological com- * BSCS High-School (ANL) to gain a detailed picture of panies are keenly interested in such ribosomal function, a team from the studies because of their potential Curriculum Modules U.K. Medical Research Council Labo- usefulness in the design of new anti- Four high-school curriculum modules ratory of Molecular Biology (LMB) biotics that can overcome the grow- produced by the Biological Sciences has developed insights into how ribo- ing problem of resistance.à Curriculum Study (BSCS) and spon- somes manufacture proteins from sored by DOE can be downloaded amino acids to the exact specification free of charge from the BSCS site of genes on DNA. Led by LMB head (www.bscs.org): Venki Ramakrishnan, the team pub- Genes, Environment, and Human lished its work in Science on May 4 Behavior (2000) [J. M. Ogle et al., Science 292(5518), 897–902]. In Memoriam The Puzzle of Inheritance (1997) Such information aids in under- alter Goad, a pioneer in The Human Genome Project: Biol- standing not only how antibiotics WDNA sequence analysis, ogy, Computers, and Privacy work but also the basis of certain died November 2, 2000. After (1996) kinds of resistance. If an antibiotic a distinguished career in theo- Mapping and Sequencing the could induce a ribosome to make a retical physics at Los Alamos Human Genome: Science, Ethics, “mistake” and add the wrong amino National Laboratory, he cre- Policy (1997) acid onto the protein chain, for exam- ated the first DNA database, All but the last also are available in ple, such incorrectly made proteins GenBank, a key event in the print at $5 each for shipping and would not function. If this happened formulation and success of the handling (BSCS, 719/531-5550, in bacteria during development, they Human Genome Project.à [email protected]).à would be rendered ineffective. 22 Human Genome News 11(3–4) July 2001

Calendar of Genome and Biotechnology Meetings*

More comprehensive lists of genome-related meetings and organizations offering training are available on the Web (www.ornl.gov/hgmis) and from HGMIS (see p. 16 for contact information).

September 2001...... 16–18. Functional Genomics; (Environ. Mut. 16. Chemical Genomics/Chemogenomics: 10–11. NIH Natl. Advisory Council for Conf. satellite meeting); Seattle [C. Aaron, High-Throughput Discovery of Disease Genes Human Genome Research; Bethesda, MD 616/833-1399, Fax: -9722; Sid.Aaron@ and Drugs; Boston [see contact, Sept. 17–19] [K. Malone, 301/402-2205, Fax: -0837; pharmacia.com; www.genomicfunctions.org] 16–18. Science and Society: From Genomes [email protected]] 17–18. Pharmacogenomics 2; Paris [Institut to Cures; Heidelberg, Germany [EMBL; 13–15. Computational Challenges in the Pasteur; [email protected]; www.pasteur.fr/ [email protected]; www-db.embl- Post-Genomic Age-II; Durham, NC applications/euroconf] heidelberg.de:4321/CoursesConferences.html] [A. Komornicki, 650/786-0003; 18–19. Pharmacogenomics and Population 27–28. BERAC Meeting; Washington, DC [email protected]; Groups; Louisville, KY [C. Rupf, 502/852-4985; [J. Corcoran, 301/903-6488; joanne.corcoran@ www.sdsc.edu/Workshops/postgenomic] [email protected]] science.doe.gov; www.sc.doe.gov/production/ 17–19. Human Genetic Variation and 18–19. Biosilico 2001: Scientific American’s ober/berac.html] Pharmacogenomics; Boston [CHI, 617/630-1300, 2nd Annu. Bioinformatics and Genomics 29–Dec. 1. 5th Annu. Conf. on Computa- Fax: -1325; [email protected]; Conf.; New York [BioEdge, 402/996-9185, tional Genomics; Baltimore [see contact, www.healthtech.com] Fax: 973/429-8234; BioSilicoInfo@ Oct. 25–28] 20. Human Genetics, Environment, and bioedge.net; www.bioedge.net] December 2001 ...... Communities of Color: Ethical and Social 18–21. Bioinformatics and Medicine. From Implications; New York [S. Prakash, Molecules to Humans, Virtual and Real; 2nd 3–4. Symp. on Gene Expression and 212/961-1000 ext. 333, Fax: -1015; confer- Bioinformatics Industrialization Workshop; Proteomics in Environmental Health [email protected]; www.weact.org/conference] Hinxton, Cambridge, UK [N. Clarkson, +44- Research; Bethesda, MD [J. Selkirk; selkirk@ 1223/495002; Fax: /495023; nicky.clarkson@ niehs.nih.gov; www.niehs.nih.gov/nct/ 24–25. Next-Generation Technologies for workshop.htm] High-Throughput Proteomics; San Francisco hinxton.wellcome.ac.uk; www.wellcome.ac.uk/ [GBR, 530/478-1523, Fax: -1773; en/1/biosersymhinscibin.html] 6–9. Physiological Genomics & Rat Models; www.annualproteomics.com] 21–24. 15th Intl. Mouse Genome Conf.; Cold Spring Harbor, NY [see contact, Sept. 28–30] 28–30. Integrating Genome Sequence, Edinburgh [D. Miller, 865/574-0858, Fax: -1283; 17–19. 12th Intl. Conf. on Genome Informa- Sequence Variation, and Gene Expression; [email protected]; www.imgc2001.com] tics; Tokyo [Secretariat, +81-3/5449-5615, Cold Spring Harbor, NY [CSHL, 516/367-8346, 24–25. Structural Genomics in Pharmaceu- Fax: -5442; [email protected]; http://giw. Fax: -8845; [email protected]; www.cshl.org] tical Design: 15th Annu. Symp. for the Cen- ims.u-tokyo.ac.jp/giw2001/index.html] ter for Advanced Biotechnol. and Medicine; January 2002...... October 2001 ...... Princeton, NJ [PTI, 609/987-0586, Fax: -0092; 3–7. Pacific Symp. on Biocomputing 2002; 5–6. Genetics Policy and Law: Natl. Forum www.genomics-bioinformatics.com] Kauai, HI [K. Lauderdale, 650/725-0659, of the Natl. Conf. of State Legislators; Wash- 25–28. Genome Sequencing and Analysis ington, DC [NCSL, 303/830-2200; ncsl_ Fax: -7944; [email protected]; Conf.; San Diego [TIGR, 301/610-5959, http://psb.stanford.edu] [email protected]; ww.ncsl.org/programs/ Fax: /838-0229; [email protected]; www.tigr.org] health/genetics/oct-meet.htm] 5–11. Structural Genomics: From Gene 28–Nov. 1. 9th Intl. Conf. on Microbial Sequence to Function; Breckenridge, CO 9–10. Functional Genomics: Using a Systems Genomes; Gatlinburg, TN [J. Zhou, Biology Approach to Develop Novel Therapeu- [970/262-1230, Fax: /1525; info@ 865/576-7544, Fax: -8646; [email protected]; keystonesymposia.org; www.symposia.com] tics; Boston [see contact, Sept. 17–19] www.esd.ornl.gov/microbial_genomes] 9–12. Genomics Meets Nanoscience; Bar 5–11. Frontiers of Structural Biology; 29–Nov. 1. Chips to Hits; San Diego [IBC, Breckenridge, CO [see contact, Jan. 5–11] Harbor, ME [N. Place, 207/288-6257, 508/616-5550, Fax: -5522; www.ibcusa.com] Fax: -6080; [email protected]; www.jax.org/ 7–13. Molecular Mechanisms of DNA Repli- courses/documents/courses_2001.html] November 2001 ...... cation and Recombination; Snowbird, UT 10–12. Genetic Nursing: Cultures, 4–7. 20th Annu. NSGC Educ. Conf.; Wash- [see contact, Jan. 5–11] Consumers, Discoveries; San Diego ington, DC [A. Lombard, 610/872-7608, 9–11. Second Annu. Human Proteome Project; [ISONG, E. Rawnsley, 603/643-5706; Fax: /565-6220; www.nsgc.org] San Diego [see contact, Sept. 17–19] [email protected]; www.nursing. 4–7. 2nd Intl. Conf. on Systems Biology; 12–16. Plant Animal & Microbe Genomes X; creighton.edu/isong/Bulletin_board/ Pasadena, CA [ICSB, 626/395-6911, San Diego [D. Scherago, 212/643-1750 Conferences] Fax: /796-8914; [email protected]; ext. 20, Fax: 1758; [email protected]; 10–13. SNP and Complex Genome Analy- www.icsb2001.org] www.intl-pag.org/pag] sis; Stockholm [A. Brookes, +46-08-7286630, 7–8. Uses of Genomic Data in Risk Assess- 20–25. Protein Folding Dynamics; Ventura, Fax: -331547; [email protected]; ment: State of the Art 2001; Washington DC CA [GRC, 401/783-4011, Fax: -7644; http://snp2001.cgr.ki.se] [Society of Toxicology, 703/438-3115; [email protected]; www.grc.uri.edu] 11–12. Applications of Genomics to Animal www.toxicology.org] 28–31. Bioinformatics Technol. Conf.; Tucson, Models for Pharmaceutical Studies; Boston 7–10. NABT 2001 Natl. Conv.; Montreal AZ [A. Calvo, 707/829-0515, ext. 441; andrewc@ [see contact, Sept. 17–19] [NABT, 703/264-9696, Fax: -7778; office@ oreilly.com; conferences.oreilly.com/biocon/ 12. 11th Intl. HUGO Mutation Database Ini- nabt.org; www.nabt.org/sup/conferences] cfp.html] tiative Meeting; San Diego [R. Horaitis; 9–12. Beyond the Identification of Transcribed February 2002 ...... [email protected]; Sequences: Functional and Expression Anal- www.genomic.unimelb.edu.au/mdi/meetings/ ysis; Washington, DC [K. Gardiner, 2–6. Genomics and Structural Biol. in Medi- sandiego.html] 303/336-5652; [email protected]; cine: Miami Nature Biotechnol. Symp.; Miami [S. Black, 305/243-3597, Fax: /324-5665; American Society of Human Genetics; www.ornl.gov/meetings/bits2001] 12–16. [email protected]; www.med.miami. San Diego [M. Ryan, 301/530-7010, 15–18. In Silico Biology: Bioinformatics edu/mnbws] Fax: -7014; [email protected]; After the Human Genome; Atlanta [Organizing www.faseb.org/meetings/] Committee, 404/385-3501, Fax: /894-8925; 10–14. 27th Annu. Lorne Conf. on Protein Structure and Function; Lorne, Australia Genomic Information: Whitehead [email protected]; 14–16. [L. Sparrow, +61-3/9662-7284, Fax: -7101; Symp. XIX; Boston [G. Cervini, 617/258-0633; http://exon.biology.gatech.edu/conference/] [email protected]; www. [email protected]; www.whitehead.mit.edu/ biochemistry.unimelb.edu.au/lorne] cee/cee_conf.html] *Dates and meeting status may change; courses may also be offered at other times and places; check with contact person. Attendance may be either limited or restricted. July 2001 Human Genome News 11(3–4) 23

For Your Information

11–12. NIH National Advisory Council for * Exploring DNA Contractor-Grantee Meeting Human Genome Research; Bethesda, MD [see contact, Sept. 10–11] in the Classroom Scheduled for DOE Human 14–19. AAAS 2002 Annu. Meeting; Boston With the support of the DOE Human Genome Program [AAAS, 202/326-6450, Fax: /289-4021; [email protected]; www.aaas.org] Genome Program, the Biotechnol- n Jan. 27–Feb. 3, 2002, in Oakland, 19–24. Genotype to Phenotype: Focus on ogy Institute has published an California (contact: Donn Davy, Disease; Santa Fe, NM [see contact, Jan. 5–11] interactive CD-ROM for 7th to 12th 510/486-4162, [email protected]) 21–26. Epigenetics in Development and grade classrooms. DNA and Genes Disease; Taos, NM [see contact, Jan. 5–11] Odyssey, which can be used on PC 22–23. The End of Natural Motherhood? The or MAC, contains seven lectures, Artificial Womb and Designer Babies; Tulsa, numerous animations, and an U.S. Genome-Related OK [S. Gelfand, 405/744-9238; Fax: -4635; extensive teacher’s guide and is Research Funding [email protected]; http://philosophy. okstate.edu/motherhood.html] accompanied by a short videotape. Investigators wishing to apply for funding are Lecture topics are “DNA and Genes urged to discuss projects with agency staff 23–24. Genomic Partnering: Emerging and before submitting proposals. Early Stage Partners; (Genome TriConference); Basics,” “Uniqueness and Inheri- Santa Clara, CA [see contact, Sept. 17–19] tance,” “Human Genome Program,” DOE Office of Biological and 25–27. Human Genome Discovery: Commer- “Genetic Testing,” “Evolutionary Environmental Research cial Implications (Genome TriConference); Biology,” “Careers,” and “Predicting Human and Microbial Genome Santa Clara, CA [see contact, Sept. 17–19] the Future.” Lecture overheads and Programs 28–Mar. 1. Gene Functional Analysis teacher materials can be displayed • Funding opportunities: www.sc.doe.gov/ (Genome TriConference); SantaClara, CA on screen or printed. A teacher survey [see contact, Sept. 17–19] à production/grants/grants.html is at http://psych.la.psu.edu/jswim/ • Life Sciences Division: bioscied/DNAandGenes.htm. 301/903-6488, [email protected] • The spring issue of Your World mag- Medical Sciences Division: 301/903-3213, [email protected] Training Calendar azine, Cracking the Code, explores the impact of the Human Genome Computational Molecular Biology Postdoctoral Fellowships September 2001...... Project. Its publication coincided Support career transitions into computational 23–Oct. 6. Molecular Biol. Techniques; with the release of a 2-hour television molecular biology from other scientific fields. Chapel Hill, NC [W. Litaker, 919/966-1730, special titled “Cracking the Code of Funded by DOE and the Alfred P. Sloan Fax: -6821; [email protected]; Life,” produced by NOVA and Foundation. www.med.unc.edu/pmbb/welcome.htm] WGBH-TV and broadcast on PBS • Contact: Pat Stanley, Sloan Foundation; 29–Oct. 6. DNA Microarrays: Applications stations (www.pbs.org/wgbh/ 212/649-1628, [email protected], and Data Analysis; Heidelberg, Germany www.sloan.org/main.shtml [EMBL; [email protected]; nova/genome). Written for 7th to www-db.embl-heidelberg.de:4321/ 10th graders, Your World is the NIH National Human Genome CoursesConferences.html] magazine of biotechnology funda- Research Institute 30–Oct. 7. Mathematical Approaches to mentals and applications in • NHGRI program: 301/496-7531, the Analysis of Complex Phenotypes; Bar healthcare, agriculture, the environ- www.nhgri.nih.gov/About_NHGRI Harbor, ME [N. Place, 207/288-6326; • [email protected]; www.jax.org/courses/ ment, and industry. The publishers Funding opportunities: documents/courses_2001.html] are preparing Cancer and Biotech- www.nhgri.nih.gov/Grant_info nology for the fall issue and Micro- • ELSI: 301/402-4997 October 2001...... bial Genomics for spring 2002. 10–23. Gene Identification: From Candi- Small Business Innovation [Contact for CD-ROM and magazine: date to Phenotype; Cold Spring Harbor, NY Research Grants 800/796-5806, jeff@biotechinstitute. [CSHL, 516/367-8346, Fax: -8845; meetings@ DOE and NIH invite small business firms cshl.org; www.cshl.org] org; www.biotechinstitute.org] (under 500 employees) to submit grant 15–28. Bioinformatics: Writing Software for Text versions of main articles and applications addressing the human genome Genome Research; Cold Spring Harbor, NY topic. The two agencies also support the Small [see contact, Oct. 10–23] the teacher’s guide for the 1997 Business Technology Transfer (STTR) program 24–26. Analysis of Gene Expression Data; Human Genome issue of Your to foster transfers between research institu- Piscataway, NJ [G. Stolovitzky, World magazine are on the Web tions and small businesses. [email protected]; http://dimacs.rutgers. (www.bio.org/library/yourworld/ Contacts: edu/Workshops/GeneExpression.html] v5iss2.htm).à • DOE SBIR/STTR Office: 301/903-1414 or 31–Nov. 5. Computational Genomics; Cold -0569, Fax: -5488, [email protected], Spring Harbor, NY [see contact, Oct. 10–23] http://sbir.er.doe.gov/sbir; DOE SBIR and STRR due February 2002. November 2001...... December 2001...... • Bettie Graham (see ELSI contact, NHGRI). 14–16. Gene Identification and Protein NIH SBIR and STTR due April 1, August 1, Introd. Molecular Biol. Computing; Functional Analysis; Hinxton, Cambridge, 3–5. and December 1. UK [Human Genome Mapping Project Cambridge, UK [see contact, Nov. 14–16] • National resources, calendar: Resource Centre, +44-1223/494-513; 10–14. Advanced Linkage Course; New www.zyn.com/sbir Fax: -512; [email protected]; York [K. Montague, 212/327-7979, www.hgmp.mrc.ac.uk] Fax: -7996; [email protected]. • National SBIR/STTR conferences: 28–30. Protein Structure Prediction; edu; http://linkage.rockefeller.edu] 360/683-5742, Fax: -5391, [email protected]. Hinxton, Cambridge, UK [see contact, 18–20. Human Linkage Analysis; London • Alerting service: http://lyris.pnl.gov/cgi-bin/ Nov. 14–16] [see contact, Nov. 14–16] à ?enter=sbir-alert à