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Offline TahoeBlue

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Battelle - Synthetic Biology
« on: May 07, 2009, 12:55:11 pm »


Nano-enabled synthetic biology

Mitchel J Doktycz1,2a and Michael L Simpson1,3,4b
Received January 29, 2007; Accepted May 24, 2007.

1Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, TN, USA
2Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
3Materials Sciences and Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
4Department of Materials Science and Engineering, University of Tennessee, Knoxville, Knoxville, TN, USA
aOak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831, USA. Tel.: +1 865 574 6204; Fax: +1 865 574 6210; E-mail: [email protected]
bOak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831, USA. Tel.: +1 865 574 8588, E-mail: [email protected]



Here, we consider the potential for a nano-enabled synthetic biology that may be derived from the confluence of systems biology and nanoscale science and technology. At this confluence, systems biology provides knowledge of the chemical components that comprise the cell and the spatial and temporal interplay between these components.

Initial efforts to mimic cells have followed a path of using soft materials that are similar or identical to cellular materials. However, the continued progress of nanoscale science and technology provides hope that many cellular attributes may be transferred to artificial systems through the control of the synthesis and assembly of hard nanoscale materials at the multiple size scales important to cellular function. In the process, advanced tools for understanding basic questions regarding biological function will be provided. Such developments could benefit both technology and science.

Cell-like complexity in nanoscale systems may lead to significantly higher levels of function, whereas also forming an experimental system that would allow a much better examination of cellular organizational principles. Here, we highlight efforts to mimic cell-like systems and the emerging tools of nanoscience that may enable an even more synthetic biology.


The initial focus in nanoscience on the synthesis of nanomaterials closes the gap between the scales of biological and synthetic systems. The next steps in nano-enabled synthetic biology will be about closing the complexity gap, which is especially challenging, as there is no general theory to guide the organization of nanoscale materials into highly interactive collectives. Instead, this field is most likely to advance through the transfer of biological principles of organization into the bottom-up synthesis of complex synthetic nanoscale materials systems. Undoubtedly, this will require the adoption of design paradigms quite different from usual engineering practice, and instead will embrace the organizational forces of excluded volume effects, stochastic modulation of nonlinear processes, scale-free networking of elements, and interconnectivity through weak and malleable interactions. Yet, these issues faced on the scale of collective behavior come full circle to present a challenge at the scale of individual nanoscale elements: can the synthesis of nanoscale materials be controlled to enhance the self-organization of highly interconnected networks? This question will drive a new emphasis on nanomaterial synthesis and the next steps in nano-enabled synthetic biology. With the continuing integration of nanoscience and technology with biological systems, a nano-enabled synthetic biology emerges and provides the tools to use the time-honored practice of design as a tool to understand complexity.


We gratefully acknowledge the staff of the Molecular-Scale Engineering and Nanoscale Technologies and the Biological and Nanoscale Systems research groups for contributions and critiques of the manuscript. Our efforts are supported by NIH Grant EB000657, the Center for Nanophase Materials Sciences, which is sponsored at Oak Ridge National Laboratory by the Division of Scientific User Facilities, US Department of Energy and the DOE Office of Science. This work was performed at the Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US DOE under Contract no. DE-AC05-00OR22725. This manuscript has been authorized by a contractor of the US Government under contract DE-AC05-00OR22725. Accordingly, the US Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for US Government purposes.

Intracellular integration of synthetic nanostructures with viable cells for controlled biochemical manipulation

Timothy E McKnight et al 2003 Nanotechnology

Timothy E McKnight1, Anatoli V Melechko2, Guy D Griffin3, Michael A Guillorn1, Vladimir I Merkulov1, Francisco Serna1, Dale K Hensley1, Mitchel J Doktycz3, Douglas H Lowndes4 and Michael L Simpson1,5

1 Molecular-Scale Engineering and Nanoscale Technology Research Group, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA
2 Department of Electrical and Computer Engineering, University of Tennessee, Knoxville, TN 37996, USA
3 Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA
4 Condensed Matter Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA
5 Materials Science and Engineering Department, University of Tennessee, Knoxville, TN 37996, USA

We demonstrate the integration of vertically aligned carbon nanofibre (VACNF) elements with the intracellular domains of viable cells for controlled biochemical manipulation. Deterministically synthesized VACNFs were modified with either adsorbed or covalently-linked plasmid DNA and were subsequently inserted into cells. Post insertion viability of the cells was demonstrated by continued proliferation of the interfaced cells and long-term (> 22 day) expression of the introduced plasmid. Adsorbed plasmids were typically desorbed in the intracellular domain and segregated to progeny cells. Covalently bound plasmids remained tethered to nanofibres and were expressed in interfaced cells but were not partitioned into progeny, and gene expression ceased when the nanofibre was no longer retained. This provides a method for achieving a genetic modification that is non-inheritable and whose extent in time can be directly and precisely controlled. These results demonstrate the potential of VACNF arrays as an intracellular interface for monitoring and controlling subcellular and molecular phenomena within viable cells for applications including biosensors, in vivo diagnostics, and in vivo logic devices.

Received 10 January 2003
Published 9 April 2003
Behold, happy is the man whom God correcteth: therefore despise not thou the chastening of the Almighty: For he maketh sore, and bindeth up: he woundeth, and his hands make whole ; He shall deliver thee in six troubles: yea, in seven there shall no evil touch thee. - Job 5

Offline TahoeBlue

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Re: Battelle - Synthetic Biology
« Reply #1 on: May 13, 2009, 12:23:13 pm »
Not directly related to Battelle, but....

Search: synthetic virus
Wednesday, 21 February, 2001, 04:15 GMT

Synthetic virus nearing reality

By BBC News Online's Jonathan Amos in San Francisco
Scientists will have the technology to create a wholly artificial virus within the next five years, a major conference in the US has been told.

The synthetic microbe could be used to help genetically engineer novel plants and animals, and treat human disease.

But if the technology is abused, it could lead to bioweapons against which society might have little defence.

The timetable for the creation of an artificial virus was laid out by Professor Clyde Hutchinson, of the University of North Carolina and The Institute of Genomic Research.

"This isn't trivial to do and no-one has yet reported doing it," he told the annual meeting of the American Association for the Advancement of Science (AAAS).

But he said: "If researchers put their minds to it, they could do it within a few years."

'Bad stuff'

Delegates to the annual meeting stressed that the issues surrounding a synthetic virus should not be over-dramatised.

Dr Jonathan Moreno, of the University of Virginia, and an author on bioweapons, said rogue states or groups already had access to plenty of destructive technologies

A synthetic virus is something to be concerned about, but the question is whether we could develop anything that is worse than what is already available in nature, that some have attempted to exploit for the purposes of bioweaponry - such as anthrax," he said.

"There's enough bad stuff out there now. So far, there is no reason to believe that this technology is going to make things any worse."

Professor Hutchinson and his fellow researchers are engaged in what is known as the Minimal Genome Project, which is investigating the smallest number of genes required to sustain life.

From scratch

The project may eventually provide the knowledge to create an artificial lifeform - most probably a small bacterium.

Such a lifeform would be built from scratch using fundamental chemicals and could be engineered to manufacture useful drug components or to break down chemicals at the site of a toxic spill.

But Prof Hutchinson told the AAAS synthetic lifeforms were still science fiction because of the difficulties in synthesising long segments of nucleic acid - the "life molecule" DNA and its chemical cousin RNA.

Most researchers would not regard a virus as being "alive", as it depends on the machinery of a living, host cell to replicate.

But its very much simpler design - nucleic acids perhaps just 10 kilobases in length and a few associated proteins - makes it an easier target for synthesis.

Although viruses are popularly seen as merely agents of disease, they also have a productive role in biotechnology.

Modified versions of viruses, in which the disease-causing elements have been "switched off", can be used to carry useful genes into an organism.

Design flexibility

Viruses could be important tools in future gene therapy, carrying genes into the cells of sick people to correct or replace the ones that have gone wrong.

A synthetic virus might make this task easier by providing greater flexibility of design.

The fear would be that the same technology could be used to synthesise a super-pathogen, or "biobomb", to terrorise society.

But Dr David Magnus, of the University of Pennsylvania Center for Bioethics, said any minded individual would probably opt for a simpler approach.

He said: "You don't have to synthesise a genome from scratch to be able to make a version of smallpox.

"You could get a close relative and use standard genetic engineering. You could probably do that right now."

Professor Daniel McGee, of Baylor University, said the threat always had to be judged against the benefits, with regulation steering us on the right course.

"We're toolmakers. The first axe could have been used for agricultural purposes and good purposes, or it could have been used for killing.

"The moral dilemma is essentially the same.

"The fact that there is more power now - it extends further than just one person with one axe - is significant, but it doesn't change the qualitative dimension of the moral dilemma."

Prof Hutchinson added: "Am I worried about a synthesised virus? No, you only worry about it if someone does it out of malicious motives."

Synthetic Polio:
Thursday, 11 July, 2002, 23:28 GMT 00:28 UK

First synthetic virus created

Scientists have assembled the first synthetic virus.
The US researchers built the infectious agent from scratch using the genome sequence for polio.

Scientists are divided about whether a virus is alive. For those that think it is, then this synthetic artefact would constitute a simple form of life.

Responding to criticisms that such research could lead to bioterrorists engineering new lethal viruses, the scientists behind the experiment said that only a few people had the knowledge to make it happen.

'New reality'

To construct the virus, the researchers say they followed a recipe they downloaded from the internet and used gene sequences from a mail-order supplier.

Having constructed the virus, which appears to be identical to its natural counterpart, the researchers, from the University of New York at Stony Brook, injected it into mice to demonstrate that it was active.

The animals were paralysed and then died.

"The reason we did it was to prove that it can be done and it now is a reality," said Dr Eckard Wimmer, leader of the biomedical research team and co-author of the study published in the journal Science.

"This approach has been talked about, but people didn't take it seriously," said Dr Wimmer.

"Now people have to take it seriously. Progress in biomedical research has its benefits and it has its down side. There is a danger inherent to progress in sciences. This is a new reality, a new consideration."

'Very easy to do'

According to researcher Jeronimo Cello, the polio virus assembled in the laboratory is one of the simplest known viruses. "It was very easy to do," he said.

The more dangerous smallpox virus would be complex and difficult to assemble, but Cello says, "it would probably in the future be possible".

Dr Wimmer added: "The world had better be prepared."

Smallpox has been eradicated in the wild, but specimens are stored in the United States and in Russia.

Dr Wimmer said assembling the polio virus showed that eradicating a virus in the wild might not mean it was gone forever because biochemists could now reconstruct those viruses from blueprints.

Following last year's terrorist and anthrax-by-mail attacks, US officials became concerned about the threat of smallpox and arranged for the manufacture of enough vaccine to protect the US population.

Matter of time

Dr CJ Peters, director for the Center for Biodefense at the University of Texas Medical Center at Galveston, said experts had known for years that it was theoretically possible to assemble a virus in the lab.

This is a new reality
Dr Eckard Wimmer  
"We've known this could be done. We've known it was just a matter of time before it was done," he said.

Dr Peters said he was concerned that publicity about a synthesized virus might lead some people to believe "that there is nothing that can be done about bioterrorism - which is not the case".

He added that it was possible that viruses like Ebola could be assembled in laboratories, but there were only a few people in the world with that skill.

Polio is on the brink of being eradicated worldwide and there are plans to stop inoculations against the disease after it disappears from nature.

Dr Wimmer said that this policy should be reconsidered. Stopping vaccination could lead to a generation of people highly susceptible to polio, enhancing its appeal as a weapon.

The World Health Organization is planning to stockpile vaccines against a return of polio and Dr Wimmer said that policy should be followed everywhere.

The Synthetic Polio Virus Research Paper:

Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template
[Research: Reports]
Cello, Jeronimo; Paul, Aniko V.; Wimmer, Eckard*

Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.
26 March 2002; accepted 25 June 2002
Published online 11 July 2002; 10.1126/science.1072266
Include this information when citing this paper.
Full-length poliovirus complementary DNA (cDNA) was synthesized by assembling oligonucleotides of plus and minus strand polarity. The synthetic poliovirus cDNA was transcribed by RNA polymerase into viral RNA, which translated and replicated in a cell-free extract, resulting in the de novo synthesis of infectious poliovirus. Experiments in tissue culture using neutralizing antibodies and CD155 receptor-specific antibodies and neurovirulence tests in CD155 transgenic mice confirmed that the synthetic virus had biochemical and pathogenic characteristics of poliovirus. Our results show that it is possible to synthesize an infectious agent by in vitro chemical-biochemical means solely by following instructions from a written sequence.
I found this interesting: HeLa (Human epithelial carcinoma cell line)

24. We thank A. Wimmer and J. Benach for valuable comments on the manuscript. We are indebted to B. L. Semler for a sample of cell-free HeLa cell extract. Supported by Contracts N65236-99-C-5835 and N65236-00-M-3707 from the Defense Advanced Research Project Agency

Public release date: 25-Nov-2008

Synthetic virus supports a bat origin for SARS

Studies establish response strategy for emerging infections

SARS – severe acute respiratory syndrome – alarmed the world five years ago as the first global pandemic of the 21st century. The coronavirus (SARS-CoV) that sickened more than 8,000 people – and killed nearly 800 of them – may have originated in bats, but the actual animal source is not known.

In an effort to understand how SARS-CoV may have jumped from bats to humans, a team of investigators from Vanderbilt University Medical Center and the University of North Carolina at Chapel Hill has now generated a synthetic SARS-like bat coronavirus. The virus – the largest replicating synthetic organism ever made – is infectious in cultured cells and mice, the researchers report in the Proceedings of the National Academy of Sciences.

The findings identify pathways by which a bat coronavirus may have adapted to infect humans. The studies also provide a model approach for rapid identification, analysis and public health responses to future natural or intentional virus epidemics.

Zoonotic viruses – animal pathogens that can cause disease in humans – pose a serious threat to public health, said Mark Denison, M.D., professor of Pediatrics at Vanderbilt and a co-leader of the research with Ralph Baric, Ph.D., professor of Epidemiology at UNC.

"It's becoming more and more clear that new human epidemics will continue to originate in animals," said Denison, who is also an associate professor of Microbiology & Immunology. "However, the mechanisms of trans-species movement and adaptation of viruses from animals to humans remain poorly understood."

At the time of the SARS epidemic, the culprit virus was rapidly identified as a coronavirus (SARS-CoV). But it didn't look like the two human coronaviruses that were known, which cause 20 percent to 30 percent of common colds, and the animal "reservoir" (the original animal host for the virus) remained elusive.

Investigators became convinced that bats were the likely source, but bat coronaviruses had never been successfully grown in culture or animals, which blocked studies of replication, evolution and prevention.

The Denison and Baric teams, with lead authors Michelle Becker, Ph.D., of Vanderbilt, and Rachel Graham Ph.D., of UNC, determined that not being able to grow the virus represented a critical gap in the ability to rapidly identify and respond to new pathogens.

To address this vulnerability, the team decided to use synthetic biology to recover a non-cultivatable virus.

"The idea is, here's the virus, or the virus group, that we think became SARS-CoV," Denison said. "Let's see if we can synthetically recover the bat virus and test it in cultured cells and in animal models – let the bat virus show us the pathways that it may have used to become a human pathogen.

"Then we would have a viable candidate virus to test for diagnostics, vaccines and treatment."

The investigators used published SARS-like bat coronavirus sequences to establish a "consensus" genome sequence – "the best bet for a virus genome that would be viable," Denison said. They then used commercial DNA synthesis and reverse genetics to "build" the consensus viral genome and several variations.

The consensus synthetic SARS-like bat CoV did not initially grow in culture. But substitution of a single small region from human SARS-CoV – the Spike protein receptor binding domain that is critical for viral entry into human cells – allowed the new chimeric SARS-like bat CoV to grow well in monkey cells (commonly used to study human SARS-CoV).

"It was a tremendous surprise that such a small region of SARS-CoV was sufficient to allow the bat virus to move from zero growth to very efficient growth in cells," Denison said.

The chimeric virus also grew well in mouse cells modified to express the receptor for SARS-CoV and in primary human airway epithelial cells. It grew poorly in mice, but a single additional change in the Spike region allowed efficient growth in mice, without causing a SARS-like disease.

The studies suggest that a very simple recombination event may have been enough to allow a coronavirus to move from one species to another, Denison said, adding that "after a virus gains the capacity to jump species, additional simple adaptations may be adequate to increase its ability to grow in the new animal host."

At all stages of design and implementation, the Vanderbilt and UNC teams acknowledged potential safety concerns and encouraged ongoing external safety reviews. Research with all bat viruses – even weakened mutants – was performed under the same stringent biosafety conditions used to study virulent SARS-CoV. The investigators found that human antibodies known to render SARS-CoV noninfectious also neutralized the bat SARS-like coronavirus, providing an additional safety measure.

"The approaches used here address fundamental questions in virus movement between species," Denison said, "and also could improve public health preparedness by allowing rapid responses to naturally emerging or intentionally introduced zoonotic pathogens."

Gee and now there is a strange Bat disease problem Humm....

White Nose Syndrome Spreads Through USA Bat Population
Written by Kay Sexton
Published on May 5th, 2009

Since 2006 an epidemic has been traveling across America, and it’s not swine flu. So called White Nose Syndrome was first identified in caves near Albany, New York, three years ago.  Since then it has spread across the northeast United States and has recently been identified in six more caves in Virginia.

The tell-tale white marking of the muzzles and ears of the bats may not even be the cause of the bat mortality—although 99% of affected bats die, and are found to have the fungal infestation—it still isn’t clear if the fungus causes the deaths or is simply an opportunist infestation of already ill animals.

Bat deaths cause insect populations to spiral
Little Brown Bat populations have had the highest mortality rate, but Eastern Pipistrelles and Northern Long-Eared Bats have also been affected and it’s not simply a question of bats dying. The effects on the ecosystem as a whole may be profound because less bats means more insects, as bats are the highest consumers of nocturnal insect life around and without them predating on local insect populations, both households and farmers may find that pest species become rampant.

This is likely to mean increased use of insecticides on crops and that economic and environmental cost will be carried by the consumer in the end.  Two species of endangered bats live in the region where the WNS has been discovered in the past month. These are Indiana Bats and Virginia Big Eared Bats. The latter has a densely populated cave system less than five miles from one of the caves where WNS has just been found.

An epidemic without a clear cause or cure

It’s still not clear what is killing the bat populations, but what is known is that bats with WNS wake up more frequently from their winter hibernation which means they use up their fat stores, forcing them to leave the caves to seek food before the insect populations are around so that they simply starve to death. It’s also unclear how WNS spreads: some experts think it travels from bat to bat, while others suggest that disoriented and weakened bats may simply seek out the nearest cave after leaving their home community, thereby transmitting the disease or condition to a new bat colony, but others believe that humans who move from cave to cave may be transmitting the infection on their clothing and equipment. As a result, caves where WNS has been confirmed are ruled off limits to recreational cavers although there is on system in place to police the warning signs placed outside caves.

Like bees, bats are dying from unknown causes
There are interesting, and worrying, parallels with the Colony Collapse Disorder being experienced by bees: in that nobody knows the exact cause, the means of transmission or what the effect of this population loss will be on the wider environment.

There are a few reasons for optimism. First, WNS is not known to directly affect humans and second, researchers have discovered that providing a heat source to bats infected with WNS may help them conserve their body heat better, meaning that they although they wake, they return to sleep when near the heat, which might be a way of keeping some infected populations alive next winter, while a definitive cure or treatment is still being sought.
Behold, happy is the man whom God correcteth: therefore despise not thou the chastening of the Almighty: For he maketh sore, and bindeth up: he woundeth, and his hands make whole ; He shall deliver thee in six troubles: yea, in seven there shall no evil touch thee. - Job 5

Offline TahoeBlue

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Re: Battelle - Synthetic Biology
« Reply #2 on: May 13, 2009, 02:03:59 pm »
7.6 Nanotechnology Safety Assessment
Activities and studies for assessing nanotechnology safety are escalating. Some noteworthy ones are: (more detailed description of each is available in the Appendix)

• the American Public Health Association has included addressing the potential safety risks of nanotechnology as one of its public health policies

• the National Nanotechnology Initiative (NNI) held a Public Meeting on Research Needs related to the Environmental, Health, and Safety Aspects of Engineered Nanoscale Materials

• the International Council on Nanotechnology has held one invitation-only workshop to develop an International Nanomaterial Environmental Health and Safety (NanoEHS) Research Needs Assessment, and plans a second workshop, to be held in Europe in Spring 2007

• “Nanotoxicology: Potential Risks and Safety Assessment”, a symposium held at Sweden's Nobel Forum, presented a wide spectrum of results related to understanding of properties and effects of nano-sized particles that have implications for occupational health

• a team from the Chinese Academy of Science's National Center for Nanoscience and Technology (NCNST) has started research into the bio-safety of artificial nano-materials

• Andrew Maynard, chief science advisor for the Project on Emerging Nanotechnologies at the Woodrow Wilson International Center, warned that safety experts are ill-equipped to handle nanotech in the workplace and proposed a middle-of-the-road approach to nanomaterial control, based on an "impact index" derived from the material's physical characteristics, and an "exposure index" related to its quantity and "dustiness"

• an International Symposium on Nanotechnology in Environmental Protection and Pollution, organized by the Asia Pacific Nanotechnology Forum, is planned for December 10-12, 2007.

Military Implications:
Relevant military personnel should review information generated by these assessments on nanotech environmental health and safety to improve military and contractor practices, as well as to assist and cooperate with the organizations working on those issues for enriching their studies.

Safety Risks of Nanotechnology. American Public Health Association (full text of the announcement in the Appendix)
Public Meeting on Research Needs and Priorities Related to the Environmental, Health, and Safety Aspects of Engineered Nanoscale Materials
ICON Research Needs Assessment Workshop

Mini-symposium on Nanotoxicology: Potential Risks and Safety Assessment,KI,Nanotox_program_final,Nov27,2006.pdf

China kicks off study on bio-safety of nanomaterials

Safety experts ill-equipped to handle nanotechnology in workplace

Nanotechnology and safety

International Symposium on Nanotechnology in Environmental Protection and Pollution ISNEPP 2007


Extreme Genetic Engineering: An Introduction to Synthetic Biology

Extreme Genetic Engineering: ETC Group Releases Report on Synthetic Biology
Behold, happy is the man whom God correcteth: therefore despise not thou the chastening of the Almighty: For he maketh sore, and bindeth up: he woundeth, and his hands make whole ; He shall deliver thee in six troubles: yea, in seven there shall no evil touch thee. - Job 5

Offline TahoeBlue

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Re: Battelle - Synthetic Biology
« Reply #3 on: July 27, 2012, 11:57:03 am »
Sexually Transmitted Bacteria Become 1st Complete 'Virtual Organism'

A microbe that causes sexually transmitted infections now has a much more awe-inspiring claim to fame: It has become the first organism to be completely simulated by a computer model.

The bug in question, Mycoplasma genitalium, is a good candidate for scientists to reconstruct using a computer, because it is truly tiny, with only 525 genes. (By comparison, humans have about 20,500 genes.)

This accomplishment opens the door for creating more complicated virtual organisms, potentially accelerating research and making it possible for bioengineers to use computers to design organisms, said lead researcher Markus Covert, a professor of bioengineering at Stanford University.
Using these computer-model organisms, researchers could test out ideas and compare their results to what is seen in living things. In particular, these virtual "organisms" could help them probe the complexity of many biological phenomena, Covert said.

For example, if so many different genes linked with cancer are known, why hasn't it been cured?

"The answer is simply cancer is not a one-gene phenomenon, it's thousands of genes interacting together, and other factors interacting in complicated ways," Covert told LiveScience. "The fact is, we won't be able to understand how those things interact together unless we use a rational, computer-based approach."

To create the model organism, Covert and colleagues combed more than 900 sources of information about the single-celled M.genitalium, which can cause inflammation of the urethra and the cervix, as well as pelvic inflammatory disease. They built a model of the organism's genetic structures and machinery for each of 28 cellular processes, such as the replication of DNA  (deoxyribonucleic acid, the code that makes up genes) and cell division. They then put these models together to simulate a whole cell.
Behold, happy is the man whom God correcteth: therefore despise not thou the chastening of the Almighty: For he maketh sore, and bindeth up: he woundeth, and his hands make whole ; He shall deliver thee in six troubles: yea, in seven there shall no evil touch thee. - Job 5

Offline TahoeBlue

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Re: Battelle - Synthetic Biology
« Reply #4 on: January 03, 2014, 07:23:36 pm »
Mystery Humans - Lord of the Rings type World
Neanderthal and Denisovan Genomes/Human and Ape Stem Cells

 Comparisons of Human and Ape Stem Cells (Alysson Muotri);
The Neandertal and Denisovan Genomes (Ed Green) Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [7/2011] [Science] [Show ID: 21955]
Comparison of Neanderthal, Cro-Magnon and Modern Human Skulls
Denisovan DNA suggests a dark complexion and interbreeding
Scientists have reconstructed the whole genetic code, or genome, of a group of ancient humans called Denisovans. They interbred with our species and the DNA results suggest they had dark hair, eyes, and skin, the journal Science reports.

In 2010, scientists from the Max Planck Institute in Germany announced the new human group based on DNA evidence from a finger bone fossil found in Denisova Cave in the Altai Mountains, Siberia.

That first DNA was obtained from mitochondria, tiny power structures in each human cell that contain their own DNA. Now, many of the same team have used a new approach and have sequenced chromosomal DNA (the DNA of the cell nucleus which contains most genes) from the same finger bone fossil.

'They were able to reconstruct the whole genome to a quality matching that obtained for living humans,' says Professor Chris Stringer, human origins expert at the Natural History Museum.
Denisovan, Neanderthal Viruses Discovered in Human DNA

Nov 20, 2013 by
Scientists from the University of Oxford and Plymouth University, both in UK, have found evidence of Neanderthal and Denisovan viruses in DNA of modern humans.

In 2012, researchers from Albert Einstein College of Medicine identified remnants of 14 ancient viruses in the genome sequences of Neanderthal and Denisovan fossils

[ ]

, dating back about 40,000 years ago. But they failed to find remnants of these viruses, belonging to the HML2 retrovirus family, in the human reference genome sequence.

In a new study, Oxford University researcher Dr Gkikas Magiorkinis with colleagues compared Neanderthal and Denisovan data to genetic data from modern-day cancer patients and managed to identify remnants of one Neanderthal and seven Denisovan viruses.

The discovery will enable scientists to investigate possible links between HML2 retroviruses and modern diseases including HIV and cancer.
Combining evolutionary theory and population genetics with cutting-edge genetic sequencing technology, the scientists will test if these viruses are still active or cause disease in modern humans.

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Published online 2008 June 18.  doi:  10.1128/JVI.00751-08
PMCID: PMC2519637

Hypermutation of an Ancient Human Retrovirus

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome, but all are remnants of ancient retroviral infections and harbor inactivating mutations that render them replication defective. Nevertheless, as viral “fossils,” HERVs may provide insights into ancient retrovirus-host interactions and their evolution
Retroviruses can become endogenous when they infect germ line cells, or their progenitors, which subsequently constitute the gametes that give rise to viable progeny.

Thereafter, endogenous retroviruses (ERVs) behave much like other host genomic DNA elements; they are inherited in a Mendelian manner and can become fixed or lost in the host population depending on their effect on the reproductive fitness of the host (40). As the presence of active, replication-competent proviruses in a host genome is most likely to be deleterious to host fitness through insertional mutagenesis, cytopathic virus production, ectopic recombination, and alteration of host gene transcription by viral promoters, endogenous retroviruses are often transcriptionally silenced

The replication cycle of a retrovirus entails the insertion ("integration") of a DNA copy of the viral genome into the nuclear genome of the host cell. Most retroviruses infect somatic cells, but occasional infection of germline cells (cells that produce eggs and sperm) can also occur. Rarely, retroviral integration may occur in a germline cell that goes on to develop into a viable organism.

This organism will carry the inserted retroviral genome as an integral part of its own genome - an "endogenous" retrovirus (ERV) that may be inherited by its offspring as a novel allele. Many ERVs have persisted in the genome of their hosts for millions of years.

However, most of these have acquired inactivating mutations during host DNA replication and are no longer capable of producing virus. ERVs can also be partially excised from the genome by a process known as recombinational deletion, in which recombination between the identical sequences that flank newly integrated retroviruses results in deletion of the internal, protein-coding regions of the viral genome
The majority of ERVs that occur in vertebrate genomes are ancient, inactivated by mutation, and have reached genetic fixation in their host species. For these reasons, they are extremely unlikely to have negative effects on their hosts except under unusual circumstances.
Researchers continue to look at a possible link between HERVs and schizophrenia, with the additional possibility of a triggering infection inducing schizophrenia
Human endogenous retrovirus (HERV) proviruses comprise a significant part of the human genome, with approximately 98,000 ERV elements and fragments making up nearly 8%.[30] According to a study published in 2005, no HERVs capable of replication had been identified; all appeared to be defective, containing major deletions or nonsense mutations

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Ancient human virus resurrected
Virus from distant past may throw light on role of retroviruses in cancer.

Researchers in France have recreated a 5-million-year-old virus whose remains are now found littered across the human genome. The ancient virus could help us to understand how these genetic remnants contribute to cancer.

The virus is of a type called a retrovirus, which can insert copies of its genetic material into our own DNA. These viruses probably infected eggs and sperm of our primate ancestors many millions of years ago, and pasted numerous copies of their genetic material into the genome. The relics of these copies in human DNA are called human endogenous retroviruses, or HERVs.
Now Thierry Heidmann at the Gustav Roussy Institute in Villejuif and his colleagues, have brought one of these retroviruses back to life. They call it Phoenix, for the mythical bird reborn from its own ashes.

"It's a Jurassic Park kind of experiment to resurrect an old virus," says John Coffin who studies retroviruses at Tufts University in Boston, Massachusetts. "It's just kind of cool."

Rising from the ashes

Heidmann's team focused on a particular type of retrovirus that infected human cells less than 5 million years ago and left a legacy of some 30 copies of itself in the modern human genome.
The team then used the DNA of two existing HERVs as a backbone and engineered specific mutations into it, to build a duplicate of the original Pheonix. They inserted it into human cells to see what it would do.

The ancestral virus was able to copy itself and manufacture new virus particles, they found. And these particles could infect fresh cells and copy and paste its genes into these cells' genome.
Dangerous infection

The team also found hints that some of the HERVs in our genomes might still be infectious. They spliced together parts of three HERVs — a process that could occur spontaneously in a cell — and found that they could also produce infectious viruses. Heidmann says that the human genome may even harbour as-yet undiscovered HERVs that are naturally infectious.
The group also engineered the virus so that it can only copy itself once and cannot proliferate out of control. "It's not impossible that it could turn out to be a pathogen but I think it's very unlikely," agrees Coffin.

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Public release date: 30-Oct-2006

Contact: Maria Smit
[email protected]
Cold Spring Harbor Laboratory

Phoenix rising: Scientists resuscitate a 5 million-year-old retrovirus

VILLEJUIF, France (Tues., Oct. 31, 2006) -- A team of scientists has reconstructed the DNA sequence of a 5-million-year-old retrovirus and shown that it is able to produce infectious particles.

The retrovirus--named Phoenix--is the ancestor of a large family of mobile DNA elements, some of which may play a role in cancer. The study, which is the first to generate an infectious retrovirus from a mobile element in the human genome, is considered a breakthrough for the field of retrovirus research. The findings are reported in Genome Research.

"Phoenix became frozen in time after it integrated into the human genome about 5 million years ago," explains Dr. Thierry Heidmann, lead investigator on the project. "In our study, we've recovered this ancestral state and shown that it has the potential for infectivity."

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Re: Battelle - Synthetic Biology
« Reply #5 on: March 27, 2014, 04:07:38 pm »
Scientists create first 'designer chromosome'
Traci Watson, Special for USA TODAY 2:32 p.m. EDT March 27, 2014
Scientists have managed to re-engineer a form of brewer's yeast in a way that could help with the development of new types of drugs.

Researchers have chopped, spliced and manipulated DNA to craft the first extensively modified "designer chromosome," a genetic structure carefully engineered to spur scientific discovery.


The work is being hailed as a bioengineering feat and an important step toward producing a complex organism with a custom-made synthetic genome, or genetic blueprint. The research paves the way for producing new medicines and even biofuels from life forms with artificial chromosomes.

Artificial chromosomes have been built before. But those were relatively faithful copies of natural chromosomes, the tiny thread-like structures made of tightly packed DNA that serve as the body's blueprints. By contrast, the new chromosome is a product of purposeful tinkering, but the yeast that carry it act like normal yeast.

Previous artificial chromosomes were "copy-and-paste, more or less. It was plagiarism with a few edit marks in it," says Adam Arkin of the University of California-Berkeley and the Lawrence Berkeley National Laboratory, who was not involved in the research. The new structure is "a serious redesign of a chromosome with lots of very clever ways of … making it more engineerable and more understandable."

The result "is a tour-de-force in synthetic biology," Boston University's James Collins, another outside researcher, says via e-mail.

The chromosome in question belongs to the humble species known as brewer's yeast, crucial for beer, bread and biotechnology. Yeast don't look much like us, but at the deepest levels of biology we belong to the same category. Both yeast and humans store their chromosomes in cellular depots called nuclei; other organisms don't.

Until now, the only synthetic DNA structures were designed for bacteria and viruses, which don't belong to the grouping that includes humans and yeast.

To build the first artificial copy of an entire yeast chromosome, an international team of researchers produced a modified version of yeast chromosome III. It's small, making it easier to copy, and it's "something of a sentimental favorite" for its role in understanding basic biology, says Jef Boeke of NYU Langone Medical Center, one of the leaders of the effort.
"That's where the real power of synthetic biology is going to come in," Boeke says. "It's evolution on hyperspeed."

Yeast are already used to manufacture biomedical products, and the ability to alter their chromosomes with such precision presents new possibilities, says Farren Isaacs of Yale University, who was not involved in the research.

Some of the design features of synIII allow for "really new and fundamental changes to these organisms," he says. "That could be important in, for example, using (them) as a factory or living foundry for producing entirely new types of drugs. … It's really exciting."
Behold, happy is the man whom God correcteth: therefore despise not thou the chastening of the Almighty: For he maketh sore, and bindeth up: he woundeth, and his hands make whole ; He shall deliver thee in six troubles: yea, in seven there shall no evil touch thee. - Job 5