Genome Research Institute Research Articles

Mass spectrometry for screening of metabolic disorders

Background/aim Inborn errors of metabolism (IEM) are a group of congenital disorders that result from deficiency of enzymes or transporters involved in different metabolic pathways in the human body. The most severe form of these disorders appears early in the neonatal period; however, most types of IEMs are responsive to treatment if started early enough before the appearance of serious complications. The introduction of mass spectrometric techniques for analysis of metabolites accumulated in IEM facilitates the early diagnosis through enabling analysis of a large number of samples in a short period of time using small sample sizes suitable for patients in the neonatal period. The aim of this study was to find out the prevalence of amino acids, fatty acids, and organic acids disorders, using mass spectrometry among Egyptian children with metabolic disorders who were referred to the Biochemical Genetics Lab, Human Genetics, and Genome Research Institute, National Research Centre, Cairo, Egypt, over a period of 9 years. Patients and methods The present study enrolled 9245 children who visited Biochemical Genetics Department, Human Genetics, and Genome Research Institute, National Research Centre Cairo, Egypt, during the period from 2013 to 2021. All children were subjected to quantitative analysis of amino acids and acylcarnitine profiles in blood, using liquid chromatography/tandem mass spectrometry, whereas qualitative analysis of organic acids was done in urine by gas chromatography/mass spectrometry. Results Of 9245 suspected patients, 552 (5.97%) patients were diagnosed with 13 different types of IEM. A total of 383 (4.1%) patients were diagnosed with aminoacidopathies, 167 (1.8%) patients were diagnosed with organic acidurias, and two (0.02%) patients were diagnosed with fatty acid oxidation disorders. Phenylketonuria is the most prevalent IEM of this study (2%) followed by maple syrup urine disease (0.98%). Conclusion The simultaneous analysis of amino acids and acylcarnitines in dried blood spots with analysis of organic acids in urine using mass spectrometry provides an integrated panel for the early detection of IEMs in early years of life, facilitating prompt provision of treatment and avoiding serious complications that can be fatal.

Finding stories in noise: Mitochondrial portraits from RAD data.

Mitochondrial DNA (mtDNA) has formed the backbone of phylogeographic research for many years; however, recent trends focus on genome-wide analyses. One method proposed for calibrating inferences from noisy next-generation data, such as RAD sequencing, is to compare these results with analyses of mitochondrial sequences. Most researchers using this approach appear to be unaware that many single nucleotide polymorphisms (SNPs) identified from genome-wide sequence data are themselves mitochondrial, or assume that these are too few to bias analyses. Here, we demonstrate two methods for mining mitochondrial markers using RAD sequence data from three South African species of yellowfish, Labeobarbus. First, we use a rigorous SNP discovery pipeline using the program stacks, to identify variant sites in mtDNA, which we then combine into haplotypes. Second, we directly map sequence reads against a mitochondrial genome reference. This method allowed us to reconstruct up to 98% of the Labeobarbus mitogenome. We validated these mitogenome reconstructions through blast database searches and by comparison with cytochrome b gene sequences obtained through Sanger sequencing. Finally, we investigate the organismal consequences of these data including ancient genetic exchange and a recent translocation among populations of L.natalensis, as well as interspecific hybridization between L.aeneus and L.kimberleyensis.

Smooth Sailing, So Far: Venter Institute Wins Early Skirmish in Lawsuit Filed by Human Longevity

Clinical OMICsVol. 5, No. 5 Smooth Sailing, So Far: Venter Institute Wins Early Skirmish in Lawsuit Filed by Human LongevityAlex PhilippidisAlex PhilippidisSearch for more papers by this authorPublished Online:11 Sep 2018https://doi.org/10.1089/clinomi.05.05.12AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 5Issue 5Sep 2018 InformationCopyright © GEN PublishingTo cite this article:Alex Philippidis.Smooth Sailing, So Far: Venter Institute Wins Early Skirmish in Lawsuit Filed by Human Longevity.Clinical OMICs.Sep 2018.16-18.http://doi.org/10.1089/clinomi.05.05.12Published in Volume: 5 Issue 5: September 11, 2018PDF download

Alternative hosts and seed transmissibility of soybean blotchy mosaic virus

The Association of African Universities (AAU), the Genomics Research Institute (GRI) at the University of Pretoria, South Africa and through the National Research Foundation Incentive Grant for Rated Scientists.

Genome reprogramming for synthetic biology

The ability to go from a digitized DNA sequence to a predictable biological function is central to synthetic biology. Genome engineering tools facilitate rewriting and implementation of engineered DNA sequences. Recent development of new programmable tools to reengineer genomes has spurred myriad advances in synthetic biology. Tools such as clustered regularly interspace short palindromic repeats enable RNA-guided rational redesign of organisms and implementation of synthetic gene systems. New directed evolution methods generate organisms with radically restructured genomes. These restructured organisms have useful new phenotypes for biotechnology, such as bacteriophage resistance and increased genetic stability. Advanced DNA synthesis and assembly methods have also enabled the construction of fully synthetic organisms, such as J. Craig Venter Institute (JCVI)-syn 3.0. Here we summarize the recent advances in programmable genome engineering tools. Open image in new window

Rgg-LIKE TRANSCRIPTIONAL REGULATORS IN STREPTOCOCCUS spp.

An ability of pathogenic bacteria to survive in different ecological niches, to successfully adapt to changing environments, to colonize different organs and tissues, and to cause numerous diseases in human and animals including severe invasive diseases is provided, in particular, by the presence of specific proteins involved in regulation of gene transcription. This review summarizes the current data on the Rgg-family (TIGR01716 family, The Institute for Genomic Research, http://www.jcvi.org) of regulatory proteins encoded by some of the low G+C gram positive bacteria such as Streptococcus gordonii, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus mutans, Streptococcus thermophilus, Streptococcus suis and Streptococcus pyogenes. Proteins of this family has helix-turn-helix (HTH) motif at N-terminus which is able to bind promoter regions of the genes and regulate their transcription. The mechanisms of Rgg-dependent transcriptional regulation and the role of certain amino acids for functioning of Rgg-like proteins are discussed. The Rgg-like regulators have evolved to regulate diverse set of genes associated with virulence, metabolism, stress response, competence, biofilm formation, etc. The Rgg-like regulators are also involved in quorum sensing. Rgg-like proteins regulate not only the genes located adjacently to rgg, but also distantly located genes. Rgg-like proteins of different bacterial species have certain sequence similarity, and it is suggested that their genes are horizontally acquired. Rgg-dependent transcriptional regulation varies in a strainand species-specific manner that supports the hypothesis of the complexity of transcriptional regulation in gram-positive bacteria. The current review also discusses the role or Rgg-like regulators in control of virulent properties of gram-positive bacteria and their interaction with human host. Given the importance of Rgg-like regulators for virulence, these proteins (their genes or transcripts) can be considered as targets for development of the novel selective agents against different bacterial infections.

The fungi that ate my house.

Ten years ago, I was a professor of cell and molecular biology at Tulane University in New Orleans, Louisiana. I was riding high on a series of recent academic honors for my work studying toxigenic molds and was looking forward to spending a sabbatical leave at The Institute for Genomic Research, now the J. Craig Venter Institute, in Maryland. Then, in August 2005, just a few weeks before I was to leave on sabbatical, Hurricane Katrina nearly destroyed my university and my city. The storm upended my comfortable life and unexpectedly sent me down a new research trajectory. ![Figure][1] ILLUSTRATION: ROBERT NEUBECKER > “As I sampled my house, wearing gloves and a mask, I started to feel sick.” The weeks after Hurricane Katrina were some of the worst of my life. My family and I had safely evacuated to New Jersey, where we had friends who could house us, but our home had been flooded and our city devastated. I suffered acute insomnia, heightened by the fact that I knew too much about mold metabolism. Fungi, the life forms that had fascinated me since childhood, secrete digestive enzymes into the environment, often turning their substrates to slime, and then reabsorb the breakdown products. They are nature's great recyclers. I hated knowing that molds were recycling the contents of my waterlogged home. More than a month after Hurricane Katrina, we flew back to New Orleans to survey the damage. When we unlocked our front door, we were greeted with fungal anarchy. Molds were growing on everything: rugs, curtains, wallpaper, upholstered furniture, and—worst of all—some of my most treasured books. The odor was overpowering. Before my return to New Orleans, I figured I might salvage something from the loss of my home if I turned it into a living laboratory. I visited Jim White, a mycologist friend at Rutgers University in New Jersey, who equipped me to sample the molds in my flooded home. I traveled with a suitcase full of sterile swabs, masks, gloves, and 10 sleeves of petri dishes filled with growth media. As I sampled my house, wearing gloves and a mask, I started to feel sick. I had to take several breaks and go outside. I began to empathize with people who claimed to have gotten sick from indoor mold exposure, a controversial condition sometimes called “sick building syndrome.” I vowed that if I ever got a functioning lab again, I would study the volatile compounds that were causing the odious smell in my house. Later that fall, Rutgers invited me to finish my sabbatical leave there. The hurricane had kept me from my original sabbatical plans, and all of the microbial cultures in my Tulane laboratory had died during the weeks without power after the storm, so it was an attractive offer. Several months later, I agreed to stay on at Rutgers as founder and associate vice president of the Office for the Promotion of Women in Science, Engineering, and Mathematics. During my first years at Rutgers, I worked on issues related to women in science while reinventing my research career. In my new laboratory, as I had promised myself after Hurricane Katrina, my team adapted genetic models to study the possible physiological effects of fungal volatile organic compounds (VOCs). We found that several common fungal VOCs are neurotoxic in a Drosophila (fruit fly) model. Somewhat surprisingly, we also found that the VOCs from the most common fungus isolated from my flooded home, a Trichoderma species, can make the plant Arabidopsis and tomatoes grow better. Although I haven't been able to demonstrate that the gases from molds contribute to sick building syndrome, I have been able to show that they have many profound physiological effects. I don't recommend experiencing a devastating hurricane and losing your home as a way to revitalize your research. Nevertheless, my science has kept me focused on future possibilities rather than on past losses. The Hurricane Katrina catastrophe has led me to what may be the best science that I have ever done. [1]: pending:yes

Nonlinear analysis of random walks: a tool to analyze nucleic acid sequences

We have performed a comparison of computer-generated random sequences with tRNAs nucleotide sequences present in Bacteria represented as random walks. Nucleotide sequence data of tRNA genes were obtained from the Institute for Genomic Research (TIGR) and the GeneBank library. Random sequence data (white noise) were obtained from the algorithm by Press and Teukolsky. Random walks of nucleotide sequences were obtained by letting the orbit walk a unit step in one of four directions (down, left, right, and up), depending upon the next base (A,C,G, and T) in the sequence, and the distances from the origin calculated. The Visual Basic routines here applied to perform the analysis are presented. Relative Lempel-Ziv complexity. Entropy (sum of the positive Lyapunov indexes) and Hurst indexes of nucleotide sequences and of computer-generated random data were evaluated over the distances of their random walk. Our data show that the values of nonlinear parameters obtained from the bacteria are lower than the values of randomly generated sequences (p<0.01, p<0.05, p<0.01), meaning that the tRNA sequence is more ordered than a pure destructured random data and it owns a “memory”. The observed deviation from pure randomness should be arisen from some constraints like the secondary structure of this biologic macromolecule and/or from the peculiar origin of this macromolecule by repeated subunits. These data indicate that evolution earlier chose nonrandom “alphabets”: order together randomness were present at the dawn of life. Our method, here presented and described, provides an efficient tool to assess the amount of order/disorder in the primary structure of nucleic acid sequences.

Novel mycosin protease MycP₁ inhibitors identified by virtual screening and 4D fingerprints.

The rise of drug-resistant Mycobacterium tuberculosis lends urgency to the need for new drugs for the treatment of tuberculosis (TB). The identification of a serine protease, mycosin protease-1 (MycP1), as the crucial agent in hydrolyzing the virulence factor, ESX-secretion-associated protein B (EspB), potentially opens the door to new tuberculosis treatment options. Using the crystal structure of mycobacterial MycP1 in the apo form, we performed an iterative ligand- and structure-based virtual screening (VS) strategy to identify novel, nonpeptide, small-molecule inhibitors against MycP1 protease. Screening of ∼485 000 ligands from databases at the Genomics Research Institute (GRI) at the University of Cincinnati and the National Cancer Institute (NCI) using our VS approach, which integrated a pharmacophore model and consensus molecular shape patterns of active ligands (4D fingerprints), identified 81 putative inhibitors, and in vitro testing subsequently confirmed two of them as active inhibitors. Thereafter, the lead structures of each VS round were used to generate a new 4D fingerprint that enabled virtual rescreening of the chemical libraries. Finally, the iterative process identified a number of diverse scaffolds as lead compounds that were tested and found to have micromolar IC50 values against the MycP1 target. This study validated the efficiency of the SABRE 4D fingerprints as a means of identifying novel lead compounds in each screening round of the databases. Together, these results underscored the value of using a combination of in silico iterative ligand- and structure-based virtual screening of chemical libraries with experimental validation for the identification of promising structural scaffolds, such as the MycP1 inhibitors.

A Conversation with J. Craig Venter, PhD

A Conversation with J. Craig Venter, PhD

From simplicity to complexity: The size of the genomes of human pathogens

Harold J. Morowitz; Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia. (e-mail: morowitz@gmu.edu) A substantial number of bacterial species have now been sequenced and show a surprising range of genome sizes. If we examine a recent table of human pathogens, the reported sizes range from 582,970 base pairs for the smallest genome of Mycoplasma genitalium to 7,010,000 base pairs for the versatile versaphile, Burkholderia multivorans. The ratio is about 12. To date, no pathogens appear above Burkholderia. The smallest, Mycoplasma genitalium, has been chosen by the Venter Institute to synthesize a cell. The largest of the listed taxa are distributed over the entire size range. The lower size range consists of obligate heterotrophs, difficult to culture and infecting various human organs. They may be genitally or orally transmitted or exchanged by other direct human-to-human contact. Phylogeny is usually determined by 16S RNA. Going outside of human pathogens, the largest genome reported is 13,033,779 base pairs for the Proteobacterium, Sorangium cellulosum or 22.4 times as large as the smallest genome. Sometime before the beginning of the Cambrian period, bacteria began to find niches within and upon the surface of the animalia. These evolved, along with the evolution of the host and changes in the bacterial genome leading to a large number of bacterial taxa that are animal pathogens or commensals. Today, we examine a group of 78 bacteria that are common human pathogens. For purposes of comparison, we note that fully functional autotrophs which are probably ancestral to all bacteria seem to require between 1.5 and 2 megabase pairs. If we look at taxa with smaller genomes, they appear to have lost gene function in three ways. First, they derive almost all necessary structural and functional monomers from the host. Hence, they have lost the genes for autotrophic synthesis. Second, they are a group having defective cell walls or complete loss of cell walls, thus robbing the immune system of targets. They are not very stable outside the host, and thus tend to be transmitted orally and genitally. These groups include Mycoplasma, Chlamydia, Treponema, Rickettsia, and Gardnerella. They survive by being minimalists living in ecosystems, where everything is supplied and they have few molecular signals to trigger the host defenses.

A Scientist and an Advocate

A Scientist and an Advocate

Correction: Molecular Epidemiology of Neisseria meningitidis Serogroup B in Brazil

There was an error in the author byline. Author Julie C. Dunning Hotopp was inadvertently excluded. The author's affiliation is: 5 J. Craig Venter Institute (JCVI), Rockville, Maryland, United States of America, and the author's current address is: Institute of Genomic Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America. The author's order in the byline is sixth and the author's contributions are: Performed the experiments, analyzed the data, and contributed reagents/materials/analysis tools.

CharProtDB: a database of experimentally characterized protein annotations

CharProtDB (http://www.jcvi.org/charprotdb/) is a curated database of biochemically characterized proteins. It provides a source of direct rather than transitive assignments of function, designed to support automated annotation pipelines. The initial data set in CharProtDB was collected through manual literature curation over the years by analysts at the J. Craig Venter Institute (JCVI) [formerly The Institute of Genomic Research (TIGR)] as part of their prokaryotic genome sequencing projects. The CharProtDB has been expanded by import of selected records from publicly available protein collections whose biocuration indicated direct rather than homology-based assignment of function. Annotations in CharProtDB include gene name, symbol and various controlled vocabulary terms, including Gene Ontology terms, Enzyme Commission number and TransportDB accession. Each annotation is referenced with the source; ideally a journal reference, or, if imported and lacking one, the original database source.

A second special issue of Standards In Genomic Sciences from the Genomic Standards Consortium

Face-to-face meetings play a central role in the birth and maturation of communities. Intensive workshops filled with presentations, discussions and working group meetings have always been at the heart of the activities of the Genomic Standards Consortium (GSC). Such work-driven meetings are a key way in which the GSC fulfils its mission. Similarly, meeting reports provide a key mechanism for preserving and disseminating the consensus built at such meetings as they describe the range of speakers and participants present, topics covered and key outcomes and priorities agreed upon by the community. This issue contains a total of nine meeting reports, all from workshops held between April and December 2010. The first four describe GSC sponsored events. The first overviews the GSC 9 workshop at the J. Craig Venter Institute (JCVI) in April 2010 [1]. This pivotal meeting in the history of the GSC was the first attempt to organize an open registration meeting (with registration fees) and drew over 90 participants, the largest GSC meeting to date. The second report overviews the GSC 10 workshop held at Argonne National Labs in October of 2010 that focused on the M5 project [2]. The next two reports describe “Metagenomics, Metadata and MetaAnalysis” (M3) workshops held at the Intelligent Systems in Molecular Biology [3] and the International Society for Microbial Ecology meetings [4], respectively in 2010. Such satellite meetings allow the GSC to introduce the consensus-products of the GSC to a wider audience and also to collect essential feedback on what the community needs. As of the GSC 8 workshop, all GSC presentations have also been recorded and uploaded to the SCIVEE site. The GSC is planning its next two workshops at the Wellcome Trust Genome Campus in Hinxton, UK in April 2011 and at the Max-Plank Institute for Marine Microbiology in Bremen, Germany in September 2011. This issue also contains the first five meeting reports in SIGS contributed by external communities. The first describes a workshop held by the wider genomic annotation community as a step towards organizing a “Critical Assessment of Functional Annotation Experiment” (CAFAE) competition [5]. The next two describe the birth and early efforts to co-ordinate a megasequencing project called the Earth Microbiome Project (EMP) [6,7]. The fourth is the inaugural meeting of the BioSharing community [8]. The fifth describes the second workshop of the “Minimum Information about a Biological or Biomedical” (MIBBI) initiative [9]. The GSC is pleased to be an active member of all of these projects. We sincerely hope this special issue of meeting reports will pave the way for meeting report contributions from a wider range of related communities dedicated to creating and maintaining consensus-driven science.

Ligands of Thermophilic ABC Transporters Encoded in a Newly Sequenced Genomic Region of Thermotoga maritima MSB8 Screened by Differential Scanning Fluorimetry

The chromosome of Thermotoga maritima strain MSB8 was found to have an 8,870-bp region that is not present in its published sequence. The isolate that was sequenced by The Institute for Genomic Research (TIGR) in 1999 is apparently a laboratory variant of the isolate deposited at the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSM 3109) in 1986. This newly sequenced region from the DSMZ culture was located between TM1848 (cbp, cellobiose phosphorylase) and TM1847 (the 3' end of a truncated ROK regulator). The new region contained seven genes: a beta glucosidase gene (bglA), three trehalose ABC transporter genes (treEFG), three xylose ABC transporter genes (xylE2F2K2), and the 5' end of a gene encoding the ROK regulator TM1847. We present a new differential scanning fluorimetry method using a low pH that was necessary to screen potential ligands of these exceptionally thermostable periplasmic substrate-binding proteins. This method showed that trehalose, sucrose, and glucose stabilized TreE, and their binding was confirmed by measuring changes in intrinsic fluorescence upon ligand binding. Binding constants of 0.024 μM, 0.300 μM, and 56.78 μM at 60°C, respectively, were measured. XylE2 ligands were similarly determined and xylose, glucose, and fucose bound with K(d) (dissociation constant) values of 0.042 μM, 0.059 μM, and 1.436 μM, respectively. Since there is no discernible phenotypic difference between the TIGR isolate and the DSMZ isolate despite the variance in their genomes, we propose that they be called genomovars: T. maritima MSB8 genomovar TIGR and T. maritima MSB8 genomovar DSM 3109, respectively.

Fine mapping and candidate gene prediction of the photoperiod and thermo-sensitive genic male sterile gene pms1(t) in rice

Pei'ai64S, an indica sterile variety with photoperiod and thermo-sensitive genic male sterile (PTGMS) genes, has been widely exploited for commercial seed production for "two-line" hybrid rice in China. One PTGMS gene from Pei'ai64S, pms1(t), was mapped by a strategy of bulked-extreme and recessive-class approach with simple sequence repeat (SSR) and insert and deletion (In-Del) markers. Using linkage analysis for the F(2) mapping population consisting of 320 completely male sterile individuals derived from a cross between Pei'ai64S and 93-11 (indica restorer) lines, the pms1(t) gene was delimited to the region between the RM21242 (0.2 cM) and YF11 (0.2 cM) markers on the short arm of chromosome 7. The interval containing the pms1(t) locus, which was co-segregated with RM6776, is a 101.1 kb region based on the Nipponbare rice genome. Fourteen predicted loci were found in this region by the Institute for Genomic Research (TIGR) Genomic Annotation. Based on the function of the locus LOC_Os07g12130 by bioinformatics analysis, it is predicted to encode a protein containing a Myb-like DNA-binding domain, and may process the transcript with thermosensory response. The reverse transcription-polymerase chain reaction (RT-PCR) results revealed that the mRNA levels of LOC_Os07g12130 were altered in different photoperiod and temperature treatments. Thus, the LOC_Os07g12130 locus is the most likely candidate gene for pms1(t). These results may facilitate not only using the molecular marker assisted selection of PTGMS genes, but also cloning of the pms1(t) gene itself.

J. Craig Venter—The Human Genome Project

American-born biochemist-geneticist J. Craig Venter is acknowledged, along with geneticist Francis Sellers Collins (1950-), as being a primary force behind the Human Genome Project. Venter, with private funding, and Collins, with public funding, independently mapped and sequenced human DNA. Their reports appeared in 2001 (one in Nature and the other in Science). A sheet of 5 stamps (Scott No. 561) issued by Palau in 1999 provides an opportunity to honor J. Craig Venter indirectly. The sheet was issued to commemorate advances in science and medicine in the 20th century. One of the stamps representing the Human Genome Project shows the overall structure of DNA. J. Craig Venter was born on October 14, 1946, in Salt Lake City, UT. He spent his youth in San Francisco, CA, where he attended high school. After high school, he joined the US Naval Medical Corps and served in Vietnam, where he provided medical care at an orphanage. After Venter returned to the United States, he enrolled as a premedical student at the University of California, San Diego. However, he soon decided to pursue a career in research. He received a BS degree in biochemistry in 1972 and a PhD degree in physiology and pharmacology in 1975, both from the University of California, San Diego. In 1976, Venter became an assistant professor of pharmacology and therapeutics at the State University of New York at Buffalo and also worked at the nearby Roswell Park Memorial Institute. His research focused primarily on the elucidation of the structure and function of adrenergic receptors and muscarinic cholinergic receptors. Venter was promoted to professor in the early 1980s. For his work on receptors, he received the Boehringer Ingelheim Muscarinic Receptor Research Award. In 1984, he became a section chief at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) in Bethesda, MD, where he worked until 1992. His work at the NIH concentrated on neurotransmitters, specifically on genes that encode for enzymes involved in the synthesis of neurotransmitters and receptors. In July 1992, Venter left the NIH and became founder and chairman of the board of The Institute for Genomic Research (TIGR), a not-for-profit genomics research institution in Rockville, MD. He served as its president until 1998. In 1998, Venter joined Applera Corporation and became president and chief scientific officer of the newly founded Celera Genomics. The goal of Celera Genomics was to become the definitive source of genomic and related medical and biological information. In January 2002, Venter stepped down as president of Celera Genomics but continued to chair its scientific advisory board. Currently, he is serving as president of J. Craig Venter Institute. Venter pioneered the use of automated gene sequencers, and in 1990, he developed “expressed sequence tags” (ESTs), a new strategy for the discovery and tagging of genes that revolutionized biological science. In this approach, complementary DNA is partially sequenced, or “tagged,” using an automated DNA sequencing machine. The resulting sequences (ESTs) are long enough for one to be distinguished from another. Venter has published more than 160 research articles and has received many awards, including being elected a fellow of several societies, such as the American Association for the Advancement of Science and the American Academy of Microbiology. In 1999, he received the Beckman Award and the Chiron Corporation Biotechnology Research Award. Efforts to bring Collins and Venter together to complete the mapping of the human genome began in late 1999. In March 2000, US President Bill Clinton (1946-) and British Prime Minister Tony Blair (1953-) made a joint declaration that all genome information should be free to the public. This announcement led to cooperation between Collins and Venter, and on June 26, 2000, Venter and Collins jointly announced that, after nearly a decade of work, both the public Human Genome Project headed by Collins and Celera Genomics headed by Venter had deciphered essentially all the genes in human DNA. The importance of the cooperation between the 2 geneticists and the genome sequencing effort is far-reaching and may result in the discovery of keys to the diagnosis and treatment of numerous diseases, from diabetes to heart disease to Alzheimer disease.

Synthetic Biology Promises Risk and Reward

In May 2010, researchers at the J. Craig Venter Institute announced the creation of the world’s fi rst synthetic organism—a bacterial host cell whose self-replicating genome was human-made. This momentous achievement raises questions regarding the potential risks and benefi ts of synthesizing genomes, and eventually, organisms. According to proponents, synthetic biology offers great promise. Some scientists suggest that the emerging fi eld could lead to advancements in individualized medicine, more effi cient vaccine and drug production, new renewable energy sources, higher-yielding and more sustainable crops, and organisms that can remediate harmful chemicals in the environment. Synthetic biology is also widely acknowledged to have the potential to adversely affect human health, the environment, and national security. The possibility for unintended environmental effects concerns Allison Snow, a professor in the Department of Evolution, Ecology, and Organismal Biology at the Ohio State University. Uncontrolled escape of synthetic organisms and the rise of new invasive species are a few of the threats, according to Snow. Given the risks, synthetic organisms will need to be thoroughly evaluated before they are moved outside contained facilities. “Ecological research takes time and funding,” Snow said during a public presentation on synthetic biology in July 2010. “This is why risk assessment research shouldn’t be left for the last minute. It should go in tandem as the development of these products is moving forward.” Policymakers recognize there are trade-offs between scientifi c advancement and societal hazard. The same day the Venter Institute’s research was published, President Barack Obama directed his newly minted Presidential Commission for the Study of Bioethical with just a few new traits—are widely considered to pose few new risks. With synthetic biology, which is an extension of genetic engineering, new GMOs like blue-green algae for biofuels could be more challenging to evaluate. We have less experience with these organisms and the newly invented traits they will have. It would be naive to assume that regulations will catch every bad idea and prevent it from happening.” Experts in ethics, biosecurity, and law also see cause for concern. Some have raised doubts about society’s ability to plan for low-probability, highimpact events, such as the release of a synthetic organism. Doubts linger about gaps in the current regulatory framework to oversee privately funded research, especially that of “do-it-yourselfers” who work outside of agencies, universities, and corporations. Even if the laws were suffi cient to cover synthetic biology products, the more important issue, warns Michael Rodemeyer, is “whether the agencies have the resources and tools they need to both assess the risks of this new technology and to manage the risks as well.” Now at the University of Virginia, Rodemeyer was formerly assistant director for environment at the White House Offi ce of Science and Technology Policy. “The challenge, though, particularly as the technology develops will be to develop guidelines that are suffi ciently cautionary, but without imposing unnecessarily expensive and cumbersome containment requirements that might hinder research.” It remains to be seen whether or how the federal government will strike a balance between scientifi c discovery and risk mitigation.

Focus for Sequencing Consortium: Select Agents, Microbial Forensics

Federal agencies now sponsor a broad variety of microbial genomic sequencing programs, making it difficult to keep up with their progress. Here is a look at one of them, launched in 2009 and targeting select agents, that is, pathogens which could be used by terrorists as weapons. This program involves five-year contracts to three institutions, with resources totaling more than $106 million, according to officials from the National Institute of Allergy and Infectious Diseases (NIAID), the federal sponsor. The awards went to the Broad Institute in Cambridge, Mass., the J. Craig Venter Institute (JCVI) in Rockville, Md., and the Institute for Genome Science (IGS) at the University of Maryland School of Medicine in Baltimore. Each of these institutes is designated a Genomic Sequencing Center for Infectious Diseases (GSCID), and together they form a consortium. The Broad Institute and JCVI each received $43.3 million, and the IGS, $20 million.