News Article | May 3, 2017
"We are so pleased that Karen has been elected to the National Academy of Sciences in recognition of her seminal work in microbial and human microbiome work," said Dr. Venter, Founder, Executive Chairman, and CEO, JCVI. "It is an honor for me to be part of this exceptional group of scientists at the National Academies which include JCVI mentors and colleagues Venter, Smith and Hutchinson. I would not have achieved this success without these individuals and the entire JCVI team," said Nelson. In addition to being an elected member of the NAS, she serves on their Board of Life Sciences. Other honors include being named ARCS Scientist of the Year 2017; a Fellow of the American Academy of Microbiology; an Honorary Professor at the University of the West Indies; and a Helmholtz International Fellow. Dr. Nelson has extensive experience in microbial ecology, microbial genomics, microbial physiology and metagenomics. Dr. Nelson has led several genomic and metagenomic efforts, and led the first human metagenomics study that was published in 2006. Additional ongoing studies in her group include metagenomic approaches to study the ecology of the gastrointestinal tract of humans and animals, studies on the relationship between the microbiome and various human and animal disease conditions, reference genome sequencing and analysis primarily for the human body, and other -omics studies. She has authored or co-authored over 170 peer reviewed publications, edited three books, and is currently Editor-in-Chief of the journal Microbial Ecology. She also serves on the Editorial Boards of BMC Genomics, GigaScience, and the Central European Journal of Biology. Nelson has been JCVI President since 2012. Prior to being appointed President, she held several other positions at the Institute, including Director of JCVI's Rockville Campus, and Director of Human Microbiology and Metagenomics in the Department of Human Genomic Medicine at JCVI. Nelson received her undergraduate degree from the University of the West Indies, and her Ph.D. from Cornell University. About J. Craig Venter Institute The JCVI is a not-for-profit research institute in Rockville, MD and La Jolla, CA dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 200 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The JCVI is a 501 (c)(3) organization. For additional information, please visit http://www.JCVI.org. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/jcvi-president-karen-nelson-elected-to-national-academy-of-sciences-300451174.html
News Article | November 17, 2016
The Human Vaccines Project and Boehringer Ingelheim are pleased to announce a three-year collaboration agreement to support their mutual objective to decode the human immune system with the aim of accelerating understanding and development of immunotherapies overall as well as better vaccines for cancer treatment. Under the terms of the agreement, Boehringer Ingelheim’s contributions to the Project will help catalyze the Project’s expanding programs. “We are tremendously honored that Boehringer Ingelheim has elected to partner with the Project, joining a growing number of leading, global biopharmaceutical companies committed to addressing the key scientific challenges impeding development of next generation vaccines and immunotherapies,” said Wayne C. Koff, Ph.D., President and CEO of the Human Vaccines Project. “Boehringer Ingelheim brings exceptional basic science and clinical research expertise in the areas of oncology and human immunology, and is at the forefront of biopharma innovation in these areas.” A revolution is ongoing in cancer immunotherapy, due to the recent realization of the importance of “checkpoints,” proteins that enable tumors to evade the immune system’s ability to kill the tumor, and novel therapeutics termed “checkpoint inhibitors” that have provided dramatic clinical benefit in managing a subset of cancers in a limited number of patients. “Despite these exciting breakthroughs, our understanding of how the immune system can best be harnessed to attack and eliminate tumors remains limited. A better understanding of the human immune system in healthy individuals as well as patients, and how best to measure and direct the immune system is needed,” said Clive R. Wood, Ph.D., Senior Corporate Vice President, Discovery Research at Boehringer Ingelheim. “We are pleased to become a partner in this groundbreaking project which offers the potential to open a new era in vaccine and immunotherapeutic development. This complements our strong commitment to cancer immunology with a pipeline that includes among others, a therapeutic cancer vaccine and next generation checkpoint inhibitors.” Within the Human Vaccines Project’s scientific network, investigators at leading academic research centers are seeking to determine the central components of the human immune system at the molecular and structural level, as well as the common rules by which the immune system generates specific and durable protective responses against a range of infectious and neoplastic diseases. Successful achievement of these goals should enable accelerated development of new and improved vaccines and therapeutics for major global diseases. “The Human Vaccines Project is one of the more promising projects to help transform the future of vaccine development and cancer immunotherapy. JCVI is pleased to be adding our bioinformatics acumen as part of this effort to help conquer some of the most devastating diseases of the 21st century,” said J. Craig Venter, Founder, Chairman and CEO of the J. Craig Venter Institute which recently joined together with the Scripps Research Institute, La Jolla Institute and UC San Diego to serve as a scientific hub for the Project. About the Human Vaccines Project The Human Vaccines Project is a non-profit public-private partnership with the mission to accelerate the development of vaccines and immunotherapies against major infectious diseases and cancers by decoding the human immune system. The Project has a growing list of partners and financial supporters including: Vanderbilt University Medical Center, the J. Craig Venter Institute, the La Jolla Institute, The Scripps Research Institute, UC San Diego, Aeras, Crucell/Janssen, GSK, Pfizer, MedImmune, Regeneron, Sanofi Pasteur, the Robert Wood Johnson Foundation and the John D. and Catherine T. MacArthur Foundation. The Project brings together leading academic research centers, industrial partners, nonprofits and governments to address the primary scientific barriers to developing new vaccines and immunotherapies, and has been endorsed by 35 of the world’s leading vaccine scientists.
News Article | October 29, 2016
Preliminary data from the world’s first national meningitis B immunisation programme with Bexsero1, launched one year ago in the UK, shows the estimated effectiveness of the vaccine at 83 percent against any meningitis B strain and 94 percent against vaccine preventable strains, for all children receiving the first two of three recommended doses 2. Reported cases of the disease have dropped 50 percent in the vaccine-eligible population in the first ten months of the programme, compared to the average number of cases over the last four years. These data were presented today by Public Health England (PHE) at the International Pathogenic Neisseria Conference (IPNC) in Manchester, UK. Uptake of the vaccine in the UK national immunisation programme is high. In more than 600,000 infants aged 0-1 year old, eligible for the vaccine, more than 90 percent received two doses. Dr. Thomas Breuer, Chief Medical Officer, GSK Vaccines commented: “We are extremely encouraged by the initial results of the UK programme, which demonstrate that Bexsero helps to protect babies in the UK from this often life-threatening disease. The data substantially advance our understanding of the impact of meningitis B vaccines in a real world setting and may help inform public health authorities around the world about their future use. The report shared provides reassurance to parents who have already vaccinated their children or wish to help protect their children from meningitis B in the future.” Invasive meningococcal B disease is the leading cause of life-threatening meningitis in the industrialised world. Although not common, invasive meningococcal B disease develops rapidly, typically amongst previously healthy children and adolescents, and results in high morbidity and mortality. Initial symptoms can often resemble flu, making it difficult to diagnose. About one in 10 of those who contract the disease will die, even with appropriate treatment. Additionally, up to 20 percent of those who survive bacterial meningitis may suffer a major physical or neurological disability (limb loss, hearing loss or seizures).3,4 Bexsaro is currently the only meningococcal B vaccine licenced in Europe. The UK national immunization programme is the first such programme for the prevention of menigitis B in the world. Bexsaro is currently the only meningococcal B vaccine licenced in Europe. The UK national immunization programme is the first such programme for the prevention of menigitis B in the world. Bexsaro is currently the only meningococcal B vaccine licenced in Europe. The UK national immunization programme is the first such programme for the prevention of menigitis B in the world.Bexsero is currently the only meningococcal B vaccine licensed in Europe. The UK national immunisation programme is the first such programme for the prevention of meningitis B in the world. Infants are immunised at two and four months of age, with a booster dose at 12 months, outside of the licensed dosing schedule*, but in line with recommendations issued by the UK advisory body on immunisation2. The data presented today demonstrate the immediate impact on meningococcal B disease rates in the eligible population following two doses of the vaccine. More data are expected as the first infants from the programme receive their booster dose later this year. Linda Glennie, head of research at the Meningitis Research Foundation said, “It is great to see this early evidence that the national meningitis B immunisation programme for children under age one is effective. We hope that other countries burdened by meningitis B will now consider protecting their people from this deadly disease. Meningitis and septicaemia can kill in hours, and leave a substantial number of survivors with life-changing after-effects. We will continue to gather evidence that will unlock expertise about meningitis B vaccination.” Incidence of meningitis B is highest in infants under one year old and the ultimate goal of meningococcal vaccination is to reduce the total burden of disease. The data presented today at IPNC shows this is now happening in the UK. GSK looks forward to further analyses from PHE on the vaccine’s effectiveness over the coming months and years. Bexsero is licensed in more than 35 countries5, including the U.S. These countries include the member states of the European Union and European Economic Area, Australia, Argentina, Chile and Uruguay, where Bexsero is approved for individuals two months of age and older, and in Canada for those aged 2 months to 17 years of age. In the U.S., Bexsero is approved for use in individuals from 10 years through 25 years of age. In Brazil, Bexsero is approved for use in individuals from two months to 50 years of age. Refer to SPC for adverse events and safety guidance. GSK – one of the world’s leading research-based pharmaceutical and healthcare companies. For further information please visit www.gsk.com. Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2015. 2 In line with the recommendations made by the Joint Committee on Vaccination and Immunisation, (JCVI). JCVI position statement on use of Bexsero® meningococcal B vaccine in the UK. March 2014. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/294245/JCVI_Statement_on_MenB.pdf 5 Watson PS, Turner DPJ. Clinical experience with the meningococcal B vaccine, Bexsero®: Prospects for reducing the burden of meningococcal serogroup B disease. Vaccine 34 (2016) 875–880 http://dx.doi.org/10.1016/j.vaccine.2015.11.057
News Article | February 1, 2017
A new proof-of-concept study by researchers from the University of California San Diego succeeded in training computers to “learn” what a healthy versus an unhealthy gut microbiome looks like based on its genetic makeup. Since this can be done by genetically sequencing fecal samples, the research suggests there is great promise for new diagnostic tools that are, unlike blood draws, non-invasive. As recent advances in scientific understanding of Parkinson’s disease and cancer immunotherapy have shown, our gut microbiomes – the trillions of bacteria, viruses and other microbes that live within us – are emerging as one of the richest untapped sources of insight into human health. The problem is these microbes live in a very dense ecology of up to 1 billion micobes per gram of stool. Imagine the challenge of trying to specify all the different animals and plants in a complex ecology like a rain forest or coral reef – and then imagine trying to do this in the gut microbiome, where each creature is microscopic and identified by its DNA sequence. Determining the state of that ecology is a classic Big Data problem, where the Big Data is provided by a powerful combination of genetic sequencing techniques and supercomputing software tools. The challenge then becomes how to mine this Big Data to obtain new insights into the causes of diseases, as well as novel therapies to treat them. The new paper, titled “Using Machine Learning to Identify Major Shifts in Human Gut Microbiome Protein Family Abundance in Disease,” was presented last month at the IEEE International Conference on Big Data. It was written by a joint research team from UC San Diego and the J. Craig Venter Institute (JCVI). At UC San Diego, it included machine learning and data scientist Mehrdad Yazdani at the California Institute for Telecommunications and Information Technology’s (Calit2) Qualcomm Institute, Biomedical Sciences graduate student Bryn C. Taylor and Pediatrics Postdoctoral Scholar Justine Debelius, as well as Rob Knight, professor in the UC San Diego School of Medicine's Pediatrics Department as well as the Computer Science and Engineering Department, and director of the Center for Microbiome Innovation, and Larry Smarr, Director of Calit2 and a professor of Computer Science and Engineering. The UC San Diego team also collaborated with Weizhong Li, an associate professor at JCVI. The work began with a genetic sequencing technique known as “metagenomics,” which breaks up the DNA of the hundreds of species of microbes that live in the human large intestine (our “gut”). The technique was applied to 30 healthy people (using sequencing data from the National Institutes of Health’s Human Microbiome Program), together with 30 samples from people suffering from the autoimmune Inflammatory Bowel Disease (IBD), including those with ulcerative colitis and with illeal or colonic Crohn’s disease. This resulted in sequencing around 600 billion DNA bases, which were then fed into the supercomputer to reconstruct the relative abundance of these species; for instance, how many E. coli are present compared to other bacterial species. Since each bacterium’s genome contains thousands of genes and each gene can express a protein, this technique made it possible to translate the reconstructed DNA of the microbial community into hundreds of thousands of proteins, which are then grouped into about 10,000 protein families. The software to carry this out was developed by Li and then run on the Gordon supercomputer at the San Diego Supercomputer Center (SDSC) using 180,000 core-hours (equivalent to running a PC 24 hours a day for 20 years). To discover the patterns hidden in this huge pile of numbers, the researchers harnessed what they refer to as “fairly out-of-the-bag” machine-learning techniques originally developed for spam filters and other data mining applications. Their goal was to use these algorithms to classify major changes in the protein families found in the gut bacteria of both healthy subjects and those with IBD, based on the DNA found in their fecal samples. The researchers first used standard biostatistics routines to identify the 100 most statistically significant protein families that differentiate health and disease states. These 100 protein families were then used as a “training set” to build a machine learning classifier that could classify the remaining 9,900 protein families in diseased versus healthy states. The goal was to find a “signature” for which protein families were elevated or suppressed in disease vs. healthy states. The process is akin to training a computer to recognize the different flavors of fruit juices – something a human toddler could do intuitively, albeit from a limited perspective. “From your past experiences drinking juice, you know the difference between orange, apple, and cranberry juice,” Taylor noted. “Your future decision about what juice you are drinking will be based on your past preferences. But it’s really hard to figure out what apple juice tastes like without experiencing it first.” They have to train the computer, in other words, to recognize what apple juice tastes like – or in this case, what a “healthy” microbiome looks like by clustering data according to bacteria. “You can try to categorize healthy and sick people by looking at their intestinal bacterial composition,” explained Taylor, “but the differences are not always clear. Instead, when we categorize by the bacterial protein family levels, we see a distinct difference between healthy and sick people. This is because proteins are the workhorses of biology, and by analyzing the proteins produced by these bacteria, we can get an idea of what the bacteria are doing in your gut." The machine-learning approach is effective, said Yazdani, precisely because it’s statistically based. “The rules are not set in stone,” he added. “What you need is past data and past experiences from patients, and then based on statistics or distribution you make your decisions. You let the data speak for itself.” Since Smarr suffers from Crohn’s disease, he has been working with Knight’s Center for Microbiome Innovation to advance research in this area. “Because of the exponential increase in the data on your daily changing gut microbiome,” noted Smarr, “it will be essential to develop new machine-learning approaches to bring the biomedically important facets to light.” In the future, the researchers hope to expand their analysis, using SDSC’s Comet supercomputer, from 10,000 protein families to one million individual genes, each of which codes for a protein which can be expressed in the gut microbiome. “Scalable methods for quickly identifying such anomalies between health and disease states will be increasingly valuable for biological interpretation of sequence data,” they wrote in the paper, which they completed in eight intense days. “We wanted a fast turn-around,” said Yazdani. “That’s really important, especially for clinical data.” Following peer review, the paper was one of only 20 percent of the 423 submissions that were accepted as regular papers for the 2016 IEEE International Conference on Big Data. The conference was held in Washington, D.C. on Dec. 5-8, 2016. Yazdani and Taylor attended and presented the paper.
News Article | March 30, 2016
Genomics entrepreneur Craig Venter has created a synthetic cell that contains the smallest genome of any known, independent organism. Functioning with 473 genes, the cell is a milestone in his team’s 20-year quest to reduce life to its bare essentials and, by extension, to design life from scratch. Venter, who has co-founded a company that seeks to harness synthetic cells for making industrial products, says that the feat heralds the creation of customized cells to make drugs, fuels and other products. But an explosion in powerful ‘gene-editing’ techniques, which enable relatively easy and selective tinkering with genomes, raises a niggling question: why go to the trouble of making new life forms when you can simply tweak what already exists? Unlike the first synthetic cells made in 20101, in which Venter’s team at the J. Craig Venter Institute in La Jolla, California, copied an existing bacterial genome and transplanted it into another cell, the genome of the minimal cells is like nothing in nature. Venter says that the cell, which is described in a paper released on 24 March in Science2, constitutes a brand new, artificial species. “The idea of building whole genomes is one of the dreams and promises of synthetic biology,” says Paul Freemont, a synthetic biologist at Imperial College London, who is not involved in the work. The design and synthesis of genomes from scratch remains a niche pursuit, and is technically demanding. By contrast, the use of genome editing is soaring — and its most famous tool, CRISPR–Cas9, has already gained traction in industry, agriculture and medicine, notes George Church, a genome scientist at Harvard Medical School in Boston, Massachusetts, who works with CRISPR. “With much less effort, CRISPR came around and suddenly there are 30,000 people practising CRISPR, if not more.” Microbiologists were just starting to characterize the bacterial immune system that scientists would eventually co-opt and name CRISPR when Venter’s team began its effort to whittle life down to its bare essentials. In a 1995 Science paper, Venter’s team sequenced the genome of Mycoplasma genitalium, a sexually transmitted microbe with the smallest genome of any known free-living organism3, and mapped its 470 genes. By inactivating genes one by one and testing to see whether the bacterium could still function, the group slimmed this list down to 375 genes that seemed essential. One way to test this hypothesis is to make an organism that contains just those genes. So Venter, together with his close colleagues Clyde Hutchison and Hamilton Smith and their team, set out to build a minimal genome from scratch, by joining together chemically synthesized DNA segments. The effort required the development of new technologies, but by 2008, they had used this method to make what was essentially an exact copy of the M. genitalium genome that also included dozens of non-functional snippets of DNA ‘watermarks’4. But the sluggish growth of natural M. genitalium cells prompted them to switch to the more prolific Mycoplasma mycoides. This time, they not only synthesized its genome and watermarked it with their names and with famous quotes, but also implanted it into another bacterium that had been emptied of its own genome. The resulting ‘JCVI-syn1.0’ cells were unveiled1 in 2010 and hailed — hyperbolically, many say — as the dawn of synthetic life. (The feat prompted US President Barack Obama to launch a bioethics review, and the Vatican to question Venter’s claim that he had created life.) However, the organism’s genome was built by copying an existing plan and not through design — and its bloated genome of more than 1 million DNA bases was anything but minimal. In an attempt to complete its long-standing goal of designing a minimal genome, Venter’s team designed and synthesized a 483,000-base, 471-gene M. mycoides chromosome from which it had removed genes responsible for the production of nutrients that could be provided externally, and other genetic ‘flotsam’. But this did not produce a viable organism. So, in a further move, the team developed a ‘design-build-and-test’ cycle. It broke the M. mycoides genome into eight DNA segments and mixed and matched these to see which combinations produced viable cells; lessons learned from each cycle informed which genes were included in the next design. This process highlighted DNA sequences that do not encode proteins but that are still needed because they direct the expression of essential genes, as well as pairs of genes that perform the same essential task — when such genes are deleted one at a time, both mistakenly seem to be dispensable. Eventually, the team hit on the 531,000-base, 473-gene design that became known as JCVI-syn3.0 (syn2.0 was a less streamlined intermediary). Syn3.0 has a respectable doubling time of 3 hours, compared with, for instance, 1 hour for M. mycoides and 18 hours for M. genitalium. “This old Richard Feynman quote, ‘what I cannot create, I do not understand’, this principle is now served,” says Martin Fussenegger, a synthetic biologist at the Swiss Federal Institute of Technology (ETH) in Zurich, Switzerland. “You can add in genes and see what happens.” With nearly all of its nutrients supplied through growth media, syn3.0’s essential genes tend to be those involved in cellular chores such as making proteins, copying DNA and building cellular membranes. Astoundingly, Venter says that his team could not identify the function of 149 of the genes in syn3.0’s genome, many of which are found in other life forms, including humans. “We don’t know about a third of essential life, and we’re trying to sort that out now,” he says. This has blown Fussenegger away. “We’ve sequenced everything on this planet, and we still don’t know 149 genes that are most essential for life!” he says. “This is the coolest thing I want to know.” Syn3.0’s lasting impact on synthetic biology is an open question. “I think it’s kind of a George Mallory moment,” says Church, referring to the English mountaineer who died in 1924 trying to become the first person to climb Mount Everest. “‘Because it’s there’ was the excuse he gave for climbing Everest.” Church says that genome-editing techniques will remain the go-to choice for most applications that require a small number of genetic alterations, whereas genome design will be useful for specialized applications, such as recoding an entire genome to incorporate new amino acids. Fussenegger thinks that genome editing will be the favoured approach for therapies, but that writing genomes from scratch will appeal to scientists interested in fundamental questions about how genomes evolve, for instance. Even Venter acknowledges that syn3.0’s genome, although new, was designed by trial and error, rather than being based on a fundamental understanding of how to build a functioning genome. But he expects fast improvements, and thinks that genome synthesis from scratch will become the preferred approach for manipulating life. “If you want to make a few changes, CRISPRs are a great tool,” he says. “But if you’re really making something new and you’re trying to design life, CRISPRs aren’t going to get you there.”
News Article | May 15, 2016
Synthetic human genomes may be produced one day, resulting in the development of an entirely artificial human being. But how close is science to creating a living, breathing human being from nothing but a mixture of chemicals? Harvard University held a closed-door meeting on the subject on May 10. Attendees, including researchers, business leaders and others, discussed ideas on developing such artificial gene sequences. Members of the press were not invited to the meetings, generating waves of controversy over what may have been discussed at the get-together. Human genomes are normally passed on from parent to child, transferring inheritable traits. Creating such a genome may be possible in as little as a decade, organizers of the meeting contend. However, even if the creation of such a genetic code transpired in the coming years, these sequences could only be placed within a cell to test the genome. This would still be a far cry from the creation of an entire synthetically formed human being. As genetic sequencing techniques become more advanced, the ability to build genomes becomes easier and less expensive. In 2003, building each block of a genetic code cost roughly 4 dollars. Just 13 years later, that cost has plummeted to just 3 cents per letter. With 3 billion base pairs, building a human genome would cost just $90 million today, versus $12 billion in 2003. At that rate, within 20 years, the cost to construct a synthetic human genome would plummet to a mere $100,000. However, some researchers believe these cost savings will only come about if a "grand challenge" is announced to drive innovation. "While we strongly agree that sustained improvements in DNA construction tools are essential for advancing basic biological science and improving public health we are sceptical that synthesising a human genome is an appropriate demand driver," Laurie Zoloth of Northwestern University and Drew Endy of Stanford University wrote. These innovations can sometimes hurt research, rather than help drive it. The development of a synthetic polio virus in 2002 generated significant backlash from the general public. The result of this was cutbacks in public funding for the development of synthetic DNA. Once the technology is available to easily and inexpensively synthesize human genomes, a bevy of ethical dilemmas will present themselves. If it is possible to sequence and produce genomes of the best and brightest people n the world, how many copies of the same sequence should be produced, and who would be able to obtain them? Will parents who wish to raise a scientist be allowed to utilize genes patterned after famed physicist Albert Einstein? What about sports-minded parents who want a child with the baseball-related skills of Red Sox slugger David Ortiz? Researchers are still a long way from the development of an entire synthetic human genome, however. The first man-made species, JCVI-syn1.0, was created in 2010. Medical researchers are still decades away from producing a single synthetic human genome. Only after that could science, theoretically, produce an entirely artificial human being. Those people who worry about the development of this technology have a long time to wait before their fears may be realized, but that day is coming. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
News Article | March 24, 2016
It may also help researchers create new bacteria tailored for making medicines and other valuable substances. The newly created bacterium has a smaller genetic code than does any natural free-living counterpart, with 531,000 DNA building blocks containing 473 genes. (Humans have more than 3 billion building blocks and more than 20,000 genes). But even this stripped-down organism is full of mystery. Scientists say they have little to no idea what a third of its genes actually do. "We're showing how complex life is, even in the simplest of organisms," researcher J. Craig Venter told reporters. "These findings are very humbling." Some of the mystery genes may be clues to discovering unknown fundamental processes of life, his colleague Clyde Hutchison III said in an interview. Both researchers, from the J. Craig Venter Institute, are among the authors of a paper on the project released Thursday by the journal Science. The DNA code, or genome, is contained in a brand-new bacterium dubbed JCVI-syn3.0. The genome is not some one-and-only minimal set of genes needed for life itself. For one thing, if the researchers had pared DNA from a different bacterium they would probably have ended up with a different set of genes. For another, the minimum genome an organism needs depends on the environment in which it lives. And the new genome includes genes that are not absolutely essential to life, because they help the bacterial populations grow fast enough to be practical for lab work. The genome is "as small as we can get it and still have an organism that is ... useful," Hutchison said. One goal of such work is to understand what each gene in a living cell does, which would lead to a deep understanding of how cells work, he said. With the new bacterium, "we're closer to that than we are for any other cell," he said. Another goal is to use such minimal-DNA microbes as a chassis for adding genes to make the organisms produce medicines, fuels and other substances for uses like nutrition and agriculture, said study co-author Daniel Gibson of Synthetic Genomics. The work began with a manmade version of a microbe that normally lives in sheep, called M. mycoides (my-KOY'-deez). It has about 900 genes. The scientists identified 428 nonessential genes, built their new genome without them, and showed that it was complete enough to let a bacterium survive. Experts not involved with the work were impressed. "I find this paper really groundbreaking," said Jorg Stulke of the University of Goettingen in Germany, who is working on a similar project with a different bacterium. In an email, he said the researchers seem to have gotten at least very close to a minimum genome for M. mycoides. Ferren Isaacs of Yale University called the work "an impressive tour de force," one that may begin to identify "a universe of minimal genomes." Explore further: First 'synthetic life': Scientists 'boot up' a bacterial cell with a synthetic genome More information: "Design and synthesis of a minimal bacterial genome," Science, DOI: 10.1126/science.aad6253
News Article | March 25, 2016
« SLAC, U Toronto team develops new highly efficient ternary OER catalyst for water-splitting using earth-abundant metals; >3x TOF prior record-holder | Main | Six automated truck platoons to compete in European Truck Platooning Challenge » Researchers from the J. Craig Venter Institute (JCVI) and Synthetic Genomics, Inc. (SGI) have designed and constructed of the first minimal synthetic bacterial cell, JCVI-syn3.0. Using the first synthetic cell, Mycoplasma mycoides JCVI-syn1.0 (created by this same team in 2010, earlier post), JCVI-syn3.0 was developed through a design, build, and test process using genes from JCVI-syn1.0. The new minimal synthetic cell contains 531,560 base pairs and just 473 genes, making it the smallest genome of any organism that can be grown in laboratory media. Of these genes 149 are of unknown biological function. By comparison the first synthetic cell, M. mycoides JCVI-syn1.0 has 1.08 million base pairs and 901 genes. A paper describing this research is being published in the journal Science by lead authors Clyde A. Hutchison, III, Ph.D. and Ray-Yuan Chuang, Ph.D., senior author J. Craig Venter, Ph.D., and senior team of Hamilton O. Smith, MD, Daniel G. Gibson, Ph.D., and John I. Glass, Ph.D. Our attempt to design and create a new species, while ultimately successful, revealed that 32% of the genes essential for life in this cell are of unknown function, and showed that many are highly conserved in numerous species. All the bioinformatics studies over the past 20 years have underestimated the number of essential genes by focusing only on the known world. This is an important observation that we are carrying forward into the study of the human genome. The research to construct the first minimal synthetic cell at JCVI was the culmination of 20 years of research that began in 1995 after the genome sequencing of the first free-living organism, Haemophilus influenza, followed by the sequencing of Mycoplasma genitalium. A comparison of these two genomes revealed a common set of 256 genes which the team thought could be a minimal set of genes needed for viability. In 1999 Dr. Hutchison led a team who published a paper describing the use of global transposon mutagenesis techniques to identify the nonessential genes in M. genitalium. Over the last 50 years more than 2,000 publications have contemplated minimal cells and their use in elucidating first principals of biology. From the start, the goal of the JCVI team was similar—build a minimal operating system of a cell to understand biology but to also have a desirable chassis for use in industrial applications. The creation of the first synthetic cell in 2010 did not inform new genome design principles since the M. mycoides genome was mostly recapitulated as in nature. Rather, it established a work flow for building and testing whole genome designs, including a minimal cell, from the bottom up starting from a genome sequence. To create JCVI-syn3.0, the team used an approach of whole genome design and chemical synthesis followed by genome transplantation to test if the cell was viable. Their first attempt to minimize the genome began with a simple approach using information in the biochemical literature and some limited transposon mutagenesis work, but this did not result in a viable genome. After improving transposon methods, they discovered a set of quasi-essential genes that are necessary for robust growth which explained the failure of their first attempt. To facilitate debugging of non-functional reduced genome segments, the team built the genome in eight segments at a time so that each could be tested separately before combining them to generate a minimal genome. The team also explored gene order and how that affects cell growth and viability, noting that gene content was more critical to cell viability than gene order. They went through three cycles of designing, building, and testing ensuring that the quasi-essential genes remained, which in the end resulted in a viable, self-replicating minimal synthetic cell that contained just 473 genes, 35 of which are RNA-coding. In addition, the cell contains a unique 16S gene sequence. The team was able to assign biological function to the majority of the genes with 41% of them responsible for genome expression information, 18% related to cell membrane structure and function, 17% related to cytosolic metabolism, and 7% preservation of genome information. However, a surprising 149 genes could not be assigned a specific biological function despite intensive study. This remains an area of continued work for the researchers. The team concludes that a major outcome of this minimal cell program are new tools and semi-automated processes for whole genome synthesis. Many of these synthetic biology tools and services are commercially available through SGI and SGI-DNA including a synthetic DNA construction service specializing in building large and complex DNA fragments including combinatorial gene libraries, Archetype genomics software, Gibson Assembly kits, and the BioXp, which is a benchtop instrument for producing accurate synthetic DNA fragments. Other authors on the paper are: Thomas J. Deerinck and Mark H. Ellisman, Ph.D., University of California, San Diego National Center for Microscopy and Imaging Research; James F. Pelletier, Center for Bits and Atoms and Department of Physics, Massachusetts Institute of Technology; Elizabeth A. Strychalski, National Institute of Standards and Technology. This work was funded by SGI, the JCVI endowment and the Defense Advanced Research Projects Agency’s Living Foundries program, HR0011-12-C-0063.
News Article | March 24, 2016
Electron micrograph image shows synthetic cell clusters of JCVI-syn3.0 cells magnified at about 15,000 times in this image released on March 24, 2016. REUTERS/Tom Deerinck and Mark Ellisman/The National Center for Imaging and Microscopy Research/University of California at San Diego/Handout via Reuters More WASHINGTON (Reuters) - Scientists on Thursday announced the creation of a synthetic organism stripped down to the bare essentials with the fewest genes needed to survive and multiply, a feat at the microscopic level that may provide big insights on the very nature of life. Genome research pioneer J. Craig Venter called the bacterial cell his research team designed and constructed the "most simple of all organisms." While the human genome possesses more than 20,000 genes, the new organism gets by with only 473. "This study is definitely trying to understand a minimal basis of life," said Venter. But the researchers said that even with such a simple organism, that understanding remained elusive. They noted that even though their organism has so few genes, they were still uncertain about the function of nearly a third of them, even after more than five years of work. The researchers predicted their work would yield practical applications in developing new medicines, biochemicals, biofuels and in agriculture. "Our long-term vision has been to design and build synthetic organisms on demand where you can add in specific functions and predict what the outcome is going to be," said Daniel Gibson, vice president for DNA technologies at Synthetic Genomics Inc, the company handling commercial applications from the research. "I think it's the start of a new era," Venter added. Venter helped map the human genome in 2001 and created the first synthetic cell in 2010 with the same team that conducted the new research. That 2010 achievement, creating a bacterial organism with a manmade genome, demonstrated that genomes can be designed on a computer, made in a laboratory and transplanted into a cell to form a new, self-replicating organism. Having created that synthetic cell, the researchers set out to engineer a bacterium by removing unessential genes. The goal was to use the fewest genes necessary for the organism to live and reproduce. Venter said initially "every one of our designs failed" because they took out too many genes, and had to restore some. Venter said one lesson was that to understand life, it is more important to look across the entirely of a genome, an organism's complete genetic blueprint, rather than at individual genes. "Life is much more like a symphony orchestra than a piccolo player. And we're applying the same philosophy now to our analysis of the human genome, where we're finding most human conditions are affected by variations across the entire genome" rather than a single gene, Venter said. The researchers said they created a minimal cell possessing the smallest genome of any self-replicating organism. They said a cell with even fewer genes could be possible although it might, for example, reproduce excruciatingly slowly. Microbiologist Clyde Hutchison of the J. Craig Venter Institute in La Jolla California, lead author of the study in the journal Science, said the goal is to figure out the functions of all the cell's genes and make a computer model to predict how it would grow and change in different environments or with additional genes. "It's important to realize there is no cell that exists where we know the functions of all the genes," Hutchison said. The environmental group Friends of the Earth expressed concern about the research, citing the lack of government regulations specific to synthetic biology and gene editing technologies. "Living organisms like bacteria are not machines to be rewired," said Dana Perls, an official of the group. "Not even the scientists know the biological function of 149 of these genes, which raises safety concerns. If we don't fully understand the science, it is more difficult to manage biosafety concerns." The research might shed light on the origins of life on Earth billions of years ago. "We may be getting hints of some early fundamental mechanisms that coincide with some of the most primitive kind of life forms," Venter said. "I think as we get the ability to explore further in the universe, my view is wherever we have the same chemical constituents, which is almost everywhere, life will happen," Venter said. "But that's a philosophical point until it's proven."
News Article | March 24, 2016
An artificial bacteria developed by researchers could pave the way for the development of artificial life. This cell, stripped down to the bare minimum needed to constitute a living organism, could also assist biologists searching for the mechanisms underpinning organisms around the world. Known as JCVI-syn3.0, these cells contain the minimum number of genes needed to multiply and carry on the basic functions of survival. The artificial microorganisms contain just 473 genes, compared with more than 20,000 in our own bodies. Despite this lack of diversity and five years of study, researchers are still uncertain what purpose one-third of the genes serve. Within the genetic code of the synthetic bacteria, 41 percent of genes code information for processes within the cell, 18 percent support cell structure, 17 percent direct metabolism within fluid of the structure, and an identical number serve to store genetic information. If the machinery of a cell is thought of as a computer, the genome is the software that directs actions of the mechanism. "Our attempt to design and create a new species, while ultimately successful, revealed that 32 percent of the genes essential for life in this cell are of unknown function ... All the bioinformatics studies over the past 20 years have underestimated the number of essential genes by focusing only on the known world. This is an important observation that we are carrying forward into the study of the human genome," said J. Craig Venter, CEO of the J. Craig Venter Institute (JCVI), which developed the new organism. The genome of JCVI-syn3.0 was constructed in eight pieces, before being spliced together in a single coherent set of genetic code. The first artificial cell, JCVI-syn1.0, was developed in 2010, but those microorganisms were not significantly different from specimens found in nature. This new synthetic bacteria could assist researchers designing biofuels, biologically-based chemicals and new medicines. Researchers are learning, over time, how DNA codes for various actions and characteristics, allowing investigators to build synthetic life forms. However, the purpose of many genes within each species remains a mystery. By building cells with a minimum amount of code, investigators hope to be better able to understand the basic mechanisms of life. Creation of the first minimal synthetic bacterial cell was profiled in the journal Science.