First Self-Replicating, Synthetic Bacterial Cell Constructed by J. Craig Venter Institute Researchers

ROCKVILLE, MD and San Diego, CA (May 20, 2010) — Researchers at the J. Craig Venter Institute (JCVI), a not-for-profit genomic research organization, published results today describing the successful construction of the first self-replicating, synthetic bacterial cell. The team synthesized the 1.08 million base pair chromosome of a modified Mycoplasma mycoides genome. The synthetic cell is called Mycoplasma mycoides JCVI-syn1.0 and is the proof of principle that genomes can be designed in the computer, chemically made in the laboratory and transplanted into a recipient cell to produce a new self-replicating cell controlled only by the synthetic genome. (from www.jcvi.org)

This research will be published by Daniel Gibson et al in the May 20th edition of Science Express and will appear in an upcoming print issue of Science.

“For nearly 15 years Ham Smith, Clyde Hutchison and the rest of our team have been working toward this publication today–the successful completion of our work to construct a bacterial cell that is fully controlled by a synthetic genome,” said J. Craig Venter, Ph.D., founder and president, JCVI and senior author on the paper. “We have been consumed by this research, but we have also been equally focused on addressing the societal implications of what we believe will be one of the most powerful technologies and industrial drivers for societal good. We look forward to continued review and dialogue about the important applications of this work to ensure that it is used for the benefit of all.”

According to Dr. Smith, “With this first synthetic bacterial cell and the new tools and technologies we developed to successfully complete this project, we now have the means to dissect the genetic instruction set of a bacterial cell to see and understand how it really works.”

To complete this final stage in the nearly 15 year process to construct and boot up a synthetic cell, JCVI scientists began with the accurate, digitized genome of the bacterium, M. mycoides. The team designed 1,078 specific cassettes of DNA that were 1,080 base pairs long. These cassettes were designed so that the ends of each DNA cassette overlapped each of its neighbors by 80bp.  The cassettes were made according to JCVI’s specifications by the DNA synthesis company, Blue Heron Biotechnology.

The JCVI team employed a three stage process using their previously described yeast assembly system to build the genome using the 1,078 cassettes. The first stage involved taking 10 cassettes of DNA at a time to build 110, 10,000 bp segments. In the second stage, these 10,000 bp segments are taken 10 at a time to produce eleven, 100,000 bp segments. In the final step, all 11, 100 kb segments were assembled into the complete synthetic genome in yeast cells and grown as a yeast artificial chromosome.

The complete synthetic M. mycoides genome was isolated from the yeast cell and transplanted into Mycoplasma capricolum recipient cells that have had the genes for its restriction enzyme removed. The synthetic genome DNA was transcribed into messenger RNA, which in turn was translated into new proteins. The M. capricolum genome was either destroyed by M. mycoides restriction enzymes or was lost during cell replication. After two days viable M. mycoides cells, which contained only synthetic DNA, were clearly visible on petri dishes containing bacterial growth medium.

The initial synthesis of the synthetic genome did not result in any viable cells so the JCVI team developed an error correction method to test that each cassette they constructed was biologically functional. They did this by using a combination of 100 kb natural and synthetic segments of DNA to produce semi-synthetic genomes. This approach allowed for the testing of each synthetic segment in combination with 10 natural segments for their capacity to be transplanted and form new cells. Ten out of 11 synthetic fragments resulted in viable cells; therefore the team narrowed the issue down to a single 100 kb cassette. DNA sequencing revealed that a single base pair deletion in an essential gene was responsible for the unsuccessful transplants. Once this one base pair error was corrected, the first viable synthetic cell was produced.

Dr. Gibson stated, “To produce a synthetic cell, our group had to learn how to sequence, synthesize, and transplant genomes. Many hurdles had to be overcome, but we are now able to combine all of these steps to produce synthetic cells in the laboratory.” He added, “We can now begin working on our ultimate objective of synthesizing a minimal cell containing only the genes necessary to sustain life in its simplest form. This will help us better understand how cells work.”

This publication represents the construction of the largest synthetic molecule of a defined structure; the genome is almost double the size of the previous Mycoplasma genitalium synthesis. With this successful proof of principle, the group will now work on creating a minimal genome, which has been a goal since 1995. They will do this by whittling away at the synthetic genome and repeating transplantation experiments until no more genes can be disrupted and the genome is as small as possible. This minimal cell will be a platform for analyzing the function of every essential gene in a cell.

According to Dr. Hutchison, “To me the most remarkable thing about our synthetic cell is that its genome was designed in the computer and brought to life through chemical synthesis, without using any pieces of natural DNA. This involved developing many new and useful methods along the way. We have assembled an amazing group of scientists that have made this possible.”

As in the team’s 2008 publication in which they described the successful synthesis of the M. genitalium genome, they designed and inserted into the genome what they called watermarks. These are specifically designed segments of DNA that use the “alphabet” of genes and proteins that enable the researcher to spell out words and phrases. The watermarks are an essential means to prove that the genome is synthetic and not native, and to identify the laboratory of origin. Encoded in the watermarks is a new DNA code for writing words, sentences and numbers. In addition to the new code there is a web address to send emails to if you can successfully decode the new code, the names of 46 authors and other key contributors and three quotations: “TO LIVE, TO ERR, TO FALL, TO TRIUMPH, TO RECREATE LIFE OUT OF LIFE.” – JAMES JOYCE; “SEE THINGS NOT AS THEY ARE, BUT AS THEY MIGHT BE.”-A quote from the book, “American Prometheus”; “WHAT I CANNOT BUILD, I CANNOT UNDERSTAND.” – RICHARD FEYNMAN.

The JCVI scientists envision that the knowledge gained by constructing this first self-replicating synthetic cell, coupled with decreasing costs for DNA synthesis, will give rise to wider use of this powerful technology. This will undoubtedly lead to the development of many important applications and products including biofuels, vaccines, pharmaceuticals, clean water and food products. The group continues to drive and support ethical discussion and review to ensure a positive outcome for society.

Funding for this research came from Synthetic Genomics Inc., a company co-founded by Drs. Venter and Smith.

Background

The research published today was made possible by previous breakthroughs at JCVI. In 2007 the team published results from the transplantation of the native M. mycoides genome into the M. capricolum cell which resulted in the M. capricolum cell being transformed into M. mycoides. This work established the notion that DNA is the software of life and that DNA dictates the cell phenotype.

In 2008 the same team reported on the construction of the first synthetic bacterial genome by assembling DNA fragments made from the four chemicals of life — ACGT. The final assembly of DNA fragments into the whole genome was performed in yeast by making use of the yeast genetic systems. However, when the team attempted to transplant the synthetic bacterial genome out of yeast and into a recipient bacterial cell, viable transplants could not be recovered.

Ethical Considerations: Since the beginning of the quest to understand and build a synthetic genome, Dr. Venter and his team have been concerned with the societal issues surrounding the work. In 1995 while the team was doing the research on the minimal genome, the work underwent significant ethical review by a panel of experts at the University of Pennsylvania (Cho et al, Science December 1999:Vol. 286. no. 5447, pp. 2087 — 2090). The bioethical group’s independent deliberations, published at the same time as the scientific minimal genome research, resulted in a unanimous decision that there were no strong ethical reasons why the work should not continue as long as the scientists involved continued to engage public discussion.

Dr. Venter and the team at JCVI continue to work with bioethicists, outside policy groups, legislative members and staff, and the public to encourage discussion and understanding about the societal implications of their work and the field of synthetic genomics generally. As such, the JCVI’s policy team, along with the Center for Strategic & International Studies (CSIS), and the Massachusetts Institute of Technology (MIT), were funded by a grant from the Alfred P. Sloan Foundation for a 20-month study that explored the risks and benefits of this emerging technology, as well as possible safeguards to prevent abuse, including bioterrorism. After several workshops and public sessions the group published a report in October 2007 outlining options for the field and its researchers.

Most recently in December of 2008, JCVI received funding from the Alfred P. Sloan Foundation to examine ethical and societal concerns that are associated with the developing science of synthetic genomics. The ongoing research is intended to inform the scientific community as well as educate our policymakers and journalists so that they may engage in informed discussions on the topic.

About the 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 400 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 legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c) (3) organization

Super-stretchable Graphene Oxide Macroscopic Fibers with Outstanding Knotability Fabricated by Dry Film Scrolling

from pubs.acs.org
Graphene oxide (GO) has recently become an attractive building block for fabricating graphene-based functional materials. GO films and fibers have been prepared mainly by vacuum filtration and wet spinning. These materials exhibit relatively high Young’s moduli but low toughness and a high tendency to tear or break. Here, we report an alternative method, using bar coating and drying of water

/GO dispersions, for preparing large-area GO thin films (e.g., 800–1200 cm2 or larger) with an outstanding mechanical behavior and excellent tear resistance. These dried films were subsequently scrolled to prepare GO fibers with extremely large elongation to fracture (up to 76%), high toughness (up to 17 J/m3), and attractive macroscopic properties, such as uniform circular cross section, smooth surface, and great knotability. This method is simple, and after thermal reduction of the GO material, it can render highly electrically conducting graphene-based fibers with values up to 416 S/cm at room temperature. In this context, GO fibers annealed at 2000 °C were also successfully used as electron field emitters operating at low turn on voltages of ca. 0.48 V/μm and high current densities (5.3 A/cm2). Robust GO fibers and large-area films with fascinating architectures and outstanding mechanical and electrical properties were prepared with bar coating followed by dry film scrolling.

DISCOVERY AND VALIDATION OF Kepler-452b

from the Astronomical Journal
dx.doi.org/10.1088/0004-6256/150/2/56

We report on the discovery and validation of Kepler-452b, a transiting planet identified by a search through the 4 years of data collected by NASA’s Kepler Mission. This possibly rocky ${1.63}_{-0.20}^{+0.23}$ ${R}_{\oplus }$ planet orbits its G2 host star every ${384.843}_{-0.012}^{+0.007}$ days, the longest orbital period for a small (${R}_{{\rm{P}}}\lt 2$ ${R}_{\oplus }$) transiting exoplanet to date. The likelihood that this planet has a rocky composition lies between 49% and 62%. The star has an effective temperature of 5757 ± 85 K and a $\mathrm{log}g$ of 4.32 ± 0.09. At a mean orbital separation of ${1.046}_{-0.015}^{+0.019}$ AU, this small planet is well within the optimistic habitable zone of its star (recent Venus/early Mars), experiencing only 10% more flux than Earth receives from the Sun today, and slightly outside the conservative habitable zone (runaway greenhouse/maximum greenhouse). The star is slightly larger and older than the Sun, with a present radius of ${1.11}_{-0.09}^{+0.15}$ ${R}_{\odot }$ and an estimated age of ~6 Gyr. Thus, Kepler-452b has likely always been in the habitable zone and should remain there for another ~3 Gyr.

New magnetic field detector could improve medical imaging

The researchers say their newly designed synthetic diamond chip is 1,000 times more efficient than older models. (from upi.com)

Researchers at MIT say they’ve designed a hyper-sensitive magnetic field detector that could be used to improve medical imaging technologies and more effectively identify contraband at security checkpoints.

Magnetic field detectors, or magnetometers, are used for metal detection, medical imaging and geological observation, but the devices as currently designed have limitations. Many require “buffer gas” chambers filled with caesium vapor, which are hefty and expensive. Some work within only a narrow frequency range.

New-magnetic-field-detector-could-improve-medical-imaging

 

The new device, detailed in the latest issue of Nature Physics, attempts to improve upon a magnetometer technique using synthetic diamonds.

A tiny synthetic diamond — smaller than one-twelfth of a thumbnail — contains trillions of minuscule defects called nitrogen vacancies (NVs). When NVs are hit with lasers, the light is absorbed and re-emitted by the nano-sized deficiencies. The light, bounced back by NVs, carried information about magnetic fields nearby.

Despite the promise of synthetic diamond chips, organizing this complex process in a compact and efficient device has proven difficult. In previous models, the process of tagging the diamonds with laser photons had proven largely inefficient. Much of the light is launched straight through the diamond, failing to become captured by one of the NVs.

Researchers at MIT found that they if they could shape and angle both the laser and diamond chip just right, they could force the laser photons to bounce around the prism until all of the light was absorbed by NVs. Their technique sees a angled laser beam shot into a sawed-off corner to square-like diamond chip.

“We gain an enormous advantage by adding this prism facet to the corner of the diamond and coupling the laser into the side,” Hannah Clevenson, a graduate student in electrical engineering, explained in a recent press release. “All of the light that we put into the diamond can be absorbed and is useful.”

The researchers say their newly designed synthetic diamond chip is 1,000 times more efficient than older models.

“What’s cool about this is that they’re using the sample itself kind of like a waveguide, to bounce the light around,” Frank Narducci, a physicist at the U.S. Naval Air Systems Command, told MIT. “Their sample is quite small. Because the laser doesn’t have to be anything particularly special, that could be small, too. So you could envision very small magnetometers. And correspondingly, you could make them very cheap.”

“BigBrain” Project Makes Terabyte Map of a Human Brain

For the first time ever a complete 3-D digital map of a post mortem human brain will be available online for neuroscientists and anyone who wants a better idea of what their grey matter really looks like. The new ultra-detailed model, consisting of a terabyte of data, is part of the European Human Brain Project, created in a joint effort by Canadian and German neuroscientists. With a resolution of 20 micrometers it’s the only model yet to go beyond the macroscopic level. At this degree of resolution cells 20 micrometers in diameter are visible. Although individual smaller cells can’t be seen, it’s possible to identify and analyze the distribution of cells into cortical areas and sub-layers. Previous brain mapping efforts had resolutions one-fiftieth as fine. (from http://spectrum.ieee.org)

“The whole point of such a modeling project is that you can then start to simulate what the brain does in normal development in children or in degeneration,” says Dr. Alan Evans, a professor of biomedical engineering at the McGill University, in Montreal. “If you wanted to look to Alzheimer’s Disease, you can examine how that brain might perform computationally in a computational model if you remove certain key structures or key connections.”

Collecting images for the project involved slicing up the brain of a once healthy 65-year-old woman into over 7000 segments, each thinner than a human hair, and then digitizing the findings. This was an especially challenging task, because, once digitized, ruptures created in the slicing process had to be detected and then corrected to develop the final model; a task done both by large amount computer analysis and by manually shifting pieces of data to their proper locations.

The BigBrain is just one of many large-scale brain mapping projects including President Obama’s recently proposed BRAIN Initiative, Paul Allen’s Brain Atlas, and the Human Connectome Project. The BigBrain is the only one to provide a complete map of an individual brain. The Human Connectome Project and BRAIN Initiative focus more on brain activity. The latter will map the connections of small groups of neurons. The former compiles thousands of MRI images from 68 volunteers to map activity, look at how individual brains vary, and see which parts of the brain are involved in specific tasks. Paul Allen’s Brain Atlas focuses more on gene expression in the brain.

Obviously an in depth model of a single post mortem brain can’t really say much about brain activity nor can it account for slight variances in the structures of individual brains, says Dr. Katrin Amunts, a professor of structural functional brain mapping at Aachen University. Think of it as a general model into which data collected from in vivo brains can be put into context.

The project is “a common basis for scientific discussions because everybody can work with this brain model and we speak about the same basic findings and we can develop new methodical aspects based on these common model of the human brain,” says Dr. Karl Zilles, a senior professor at the Jülich-Aachen Research Alliance.

BigBrain pushes the limits of today’s technology, as software doesn’t yet exist to place data from multiple brains into a single model at 20-micrometer resolution. A 1-micrometer model could take up 20 to 22 petabytes of data, an amount that no computer today would be able to process, according to Amunts.

Replication attempts are heating up cold fusion

 

In just a few weeks, the whole landscape of cold fusion and LENR has changed significantly and, as many have noted, 2015 might bring a breakthrough for LENR in general, with increased public awareness, scientific acceptance and maybe even commercial applications. This is great news. (from http://animpossibleinvention.com )

cold_fusion_parkhomov_device

Most important is the apparent replication of the E-Cat phenomenon by the Russian scientist Alexander Parkhomov. On December 25, 2014, Parkhomov, a respected and experienced physicist, published a short report [1] on an experiment where he had used a reactor similar to the one used by the Swedish-Italian group in the Lugano experiment with Rossi’s E-Cat, and with similar materials in the fuel.

Parkhomov reported significant excess heat from a very small amount of fuel, just like in like other LENR experiments, and the amount of released energy was in the range of kilowatts just like with Rossi’s devices, which sets them apart from most other LENR experiments. Although the report was more of research notes than a scientific paper, the method was so simple and straight forward that it was quite convincing. Obviously it was also important that Parkhomov had performed his experiment without any contact with Rossi or the experimenters at Lugano.A review of Parkomov’s report is made by long time LENR researcher Michael McKubre in the magazine Infinite Energy. Meanwhile Parkhomov has held two seminars in Russia on his findings, and he has released a second, updated report.

Parkhomov’s report has inspired other groups to attempt a similar replication of the E-Cat effect. Martin Fleischmann Memorial Project had already planned a similar experiment, and the group is now ready to start this work, with support from Parkhomov.

Renowned LENR researcher Brian Ahern has also plans for a similar experiment.

It’s also known that the Swedish-Italian group that performed the Lugano experiment is working on continued investigations of the effect.

Apart from these, there are most probably many others who are trying the same thing without giving notice.

Apparently the interest is great all over the world. The increased interest has also been reflected in more media reports than before. One of them is a recent piece in Wired UK, noting that “if Parkhomov’s work can be copied, the Chinese may not need a licence.”

Some useful knowledge of this kind might come out of the collaboration between MFMP and the Italian researcher Francesco Piantelli, who used to work together with late Prof. Sergio Focardi before Focardi started to help Rossi.

MFMP went to see Piantelli in his lab in Tuscany, Italy, in January 2015. MFMP had a good contact with Piantelli, learning a lot from his long experience of LENR systems with nickel and hydrogen, which are different from the kind of system Rossi, even though the main elements are the same.

It’s a good thing that MFMP sticks to the idea of open science, publishing results and experiments in real time, and that the members have declared that they will never sign any kind of NDA. In this way, there’s good hope for new knowledge being communicated to other interested researchers, and that the this knowledge might grow significantly over time.All in all, things are starting to move, and they might move very fast now. On the other hand it seems that we will not get much information from Rossi and his industrial partner Industrial Heat during 2015.

Rossi still claims that he and IH are working with a 1 megawatt plant installed at the premises of a customer on commercial terms, but that they will not be ready to show the working plant until it has been running for a year.

There’s no way to confirm this.

1. cold_fusion_parkhomov_device