J. Craig Venter - Articles - Zimbio

The "bad boy" of science - Craig Venter

Mon, 22 Jul 2008 01:25:30 GMT

posted by dartboard

Innovation in energy is a must if we want to inhabit this earth for a long long time to come! Craig Ventor hopes to create an energy bug - a Bacterium that will eat Carbon Dioxide and produce fuel - the ultimate biofuel and potentially the most important energy invention of the century. "The field of synthetic genomics has the potential for groundbreaking scientific advances regarding energy invention, including the development of alternative energy sources, and the production of new vaccines and pharmaceuticals," claimed Dr. Venter.

Craig Venter discovered more than a million new genes and 1,800 new species by collecting microbes in the Sargasso Sea. Among them are organisms that thrive on carbon dioxide. Venter hopes to re-engineer some of these unique microbes genetically, into "designed species" that may reduce environmental CO2 levels, as well as provide new foods and energy sources. "Biology can do much more sophisticated chemistry than the best chemists," says Venter.

The "bad boy" of science - Craig Venter

Energy Crisis

Wed, 17 Jul 2008 17:25:08 GMT

posted by dartboard
Craig Venter decoded the human genome faster and cheaper than anyone else. He secured his place in the scientific firmament in 2000 when he nearly outran the U.S. government in the race to map the human genome.

His next goal - to replace the petrochemical industry!

By manipulating chromosomes he hopes to create an energy bug; a bacterium that will ingest CO2, sunlight and water, and spew out liquid fuel.

Dr Venter says, eventually, these life forms could be designed to make biofuels and absorb greenhouse gases.

Craig Venter has trawled for microbes in the Sargasso Sea and discovered more than a million new genes and 1,800 new species. Among them are organisms that thrive on carbon dioxide. Venter hopes to re-engineer some of these unique microbes genetically, into "designed species" that may reduce environmental CO2 levels,

as well as provide new foods and energy sources.

One project he's working on would use altered microbes to metabolize coal in the ground

and generate methane, for a tenfold increase in carbon efficiency. Another project proposes a "4th generation biofuel," where engineered algae directly convert CO2 into hydrogen in bioreactors.

Energy Invention

A Brief Bit More on Reductive Evolution in M. leprae

Thu, 13 Jun 2008 02:53:00 GMT

posted by tims3429
In a previous post I discussed the evidence for reductive evolution in Mycobacterium leprae, an interesting obligate intracellular parasite.

At the 2008 ASM General Meeting, the Division U keynote lecture was headed by Tom Gillis of the National Hansen's Disease Program. His talk described the same work I cited in the previous article, which showed the immense amount of pseudogenes in the M. leprae genome.

Gillis was interested in elucidating the role of these pseudogenes. This included asking whether or not these genes are transcribed and translated. If these pseudogenes are not providing any function, then it stems that the cells will not put energy towards their expression.

The work he discussed showed that ~44% of all M. leprae transcription was due to pseudogene expression. There doesn't appear to be a locational bias for pseudogene transcription either. Looking closely at 10 pseudogenes downstream of full-length genes, only 8 produced full-length transcripts.

More indepth in silico analysis shows that all these pseudogenes are unilogs (no duplicates present in the M. leprae genome), the vast majority lack a strong Shine-Delgarno sequence upstream, ~75% lack a translational start codon, and ~98% have one or more in-frame stop codons inserted.

This indicates that a very small percentage of pseudogene transcripts actually create a full-length translational product. So, although the cells still create the transcript, few (if any) resources are put towards creating a functional (or detrimental) protein product.

I also picked up some interesting epidemiological facts of the M. leprae genome. For one, the global M. leprae population is nearly clonal (1 polymorphism to 20,000bp compared to 1:5000 for M. tb.). However, variation in SNPs can be seen in local populations. In looking at ~60 cases from a town in India, the bug had a higher rate of diversity than compared to 3 cases in the South Eastern US or to 20 wild armadillos. Furthermore, the US cases and the wild armadillo cases were strikingly similar on an SNP scale.

I think an important point to take home from this is that M. leprae is still an evolving organism, and we are only catching a snapshot in time. It is a prime example of a parasite that has come to depend greatly on its host and has lost the ability to function outside said host.

Other articles of mine that may be of interest
Reductive Evolution in Mycobacterium Leprae
Evolution of Phage Capsid and Genome Size (Another 2008 ASM General Meeting Lecture)

Reductive Evolution in Mycobacterium leprae

Fri, 22 Mar 2008 17:36:00 GMT

posted by tims3429
Mycobacterium leprae is quite an interesting bug. It is significantly related to M. tuberculosis (the causative agent of TB), yet leprosy is a very different illness.

Unlike other mycobacteria, M. leprae is unique in the fact that it is an obligate intracellular parasite. Replication of the bacterium cannot occur outside of host cells. To date, no synthetic media has been able to support M. leprae replication. Since M. leprae is required to parasitize, it stands to reason that discovering the genetic components of this lifestyle will provide possible venues for drug therapy against this debilitating illness.

It is clear that M. leprae is closely related to the other mycobacteria, this paperby Cole et al. analyzes the genetic sequence of M. leprae and compares it to M. tuberculosis. By doing this, we have the potential to deduce how M. leprae has evolved and which genes are essential for mycobacterial replication outside of host cells.

One of the first things we see is that M. leprae has a 1.6Mbp SMALLER genome than M. tb. (~3.2Mbp and ~4.4Mbp, respectively). Of this much smaller genome in M. leprae, only about 50% of it contains protein coding genes (compared to 90% in M. tb.). The rest of the M. leprae genome is 27% recognizable pseudogenes (with a number of 1,116 compared to only 6 pseudogenes in M. tb. ) and 23% non-coding sequence (possibly as regulatory elements or genes mutated beyond recognition).

It is clear that there has been a tremendous amount of downsizing in the M. leprae genome. The large loss of sequence, along with the large amount of pseudogenes, the low number of protein coding genes, and the huge amount of non-coding sequence all indicate that M. leprae has undergone a clear and classical example of reductive evolution.

The authors go into much specificity about which genes and pathways have been lost in M. leprae compared to M. tb. One highlight is that the central metabolism of M. leprae is much different than in other mycobacteria because of a variety of gene losses. M. leprae can not utilize acetate or galactose as a carbon source. Also, it has lost all enzymes needed to function in an anaerobic or microaerophilic environment. Even it’s aerobic electron transport chain has been truncated—indicating that it can not produce ATP from NADH, and it needs to rely on low energy gain pathways to recycle its reducing equivalents.

In looking at virulence genes, the authors found only one a laminin-binding protein which may cause a tropism for myelin-producing cells (which M. leprae has). However, M. tb. also has this gene, so it’s purpose is not yet known.

M. leprae also has a handful of genes that are not present in M. tb., including eukaryotic like adenylate cyclase and uridine phosphorylase. Also, two transport systems an ABC sugar transporter and a unique divalent metal ion transport system.

I am interested to see how this study affects future drug development for anti-leprosy drugs. Also, this study should help M. tb. researchers, due to the fact that essential genes are likely conserved in these two species. With the advent of MDR and XDR-strains of M. tb. and the persistence of M. leprae in our population, it is imperative that new methods of treatment be developed.

Cole, S.T., Eiglmeier, K., Parkhill, J., James, K.D., Thomson, N.R., Wheeler, P.R., HonorÃ©, N., Garnier, T., Churcher, C., Harris, D., Mungall, K., Basham, D., Brown, D., Chillingworth, T., Connor, R., Davies, R.M., Devlin, K., Duthoy, S., Feltwell, T., Fraser, A., Hamlin, N., Holroyd, S., Hornsby, T., Jagels, K., Lacroix, C., Maclean, J., Moule, S., Murphy, L., Oliver, K., Quail, M.A., Rajandream, M., Rutherford, K.M., Rutter, S., Seeger, K., Simon, S., Simmonds, M., Skelton, J., Squares, R., Squares, S., Stevens, K., Taylor, K., Whitehead, S., Woodward, J.R., Barrell, B.G. (2001). Massive gene decay in the leprosy bacillus. Nature, 409(6823), 1007-1011. DOI: 10.1038/35059006

Microbesoft: The Controversy Over Patenting Synthetic Life

Sun, 17 Dec 2007 08:05:00 GMT

posted by starling

Activists and researchers alike are concerned that patents involving the new technology of creating synthetic life could lock up exciting new avenues of bio-research solely for commercial gain. J. Craig Venter, a pioneer of such research, is praised as an innovator and criticized as an arrogant egomaniac. But hey, if you’ve created life, wouldn’t it be tempting to see yourself as a God?

The term “synthetic” life could be considered a misnomer, however. The process of taking an existing cell, wiping out its genome, and then replacing it with a synthesized genome could be considered an engineered variation of existing life, although the implications are impressive in either case. Now rumors are circulating that Venter's group has already achieved this feat, and are only awaiting publication of a scientific paper before making the formal announcement. Earlier this year, Venter publicly stated that his team was very close to success, which he said “will be one of the bright milestones in human history, changing our conceptual view of life.”

But others don’t see current developments from such a “bright” perspective. Patent applications by Venter and his associates were filed in November, for Synthetic genomes and Installation of genomes or partial genomes into cells or cell-like systems. One clause mentions "obtaining a genome that is not within a cell; and introducing the genome into a cell or cell-like system." 17 other clauses expand that claim to nearly every other imaginable form of potential for DNA or membrane-contained space. Other clauses expand the claim about DNA to a huge range of DNA molecule sizes, including most of the sizes convenient for biologists to work with.

The ETC Group, and others, claims this is an unfair attempt by Ventor’s group to dominate synthetic life. They believe Venter’s group is attempting to create a "Microbesoft" monopoly that will significantly hinder the field of bioresearch.

"It appears that Craig Venter's lawyers have constructed a legal rats' nest of monopoly claims that may entangle the entire field of synthetic biology," ETC's Jim Thomas said in a statement.

Due to vague phrasing, the patents could even potentially cover somatic cell nuclear transplant, a technique for creating embryonic stem cells, for example. Researchers worry that the patents overlap in several key areas with existing work. If licensing issues do crop up, it’s likely that a barrage of university and biotech industry lawyers would quickly (and most likely successfully) challenge the validity of such far-reaching patents.

Aside from the controversial patenting issues. An equally heated controversy circles around whether synthetic life technology poses too many risks to justify any potential benefits in the first place. Nobel Prize winner David Baltimore has noted one of the many concerns of synthetic biology.

“I think viruses are the major focus of concern,” explained Baltimore in a Technology Review interview. “They are relatively simple to make and control and some are quite lethal. Smallpox, for example, is very potent, and we are not protected against it. The smallpox sequence is published, so you could recover it by synthesis if you had the lab facilities to do that. But getting the pieces of DNA to make smallpox is not a backyard experiment. You need a large lab with significant bio-safety precautions. I don't see this as something that would happen clandestinely in the U.S., but a well-funded lab outside of this country could do something quite nefarious.”

However, the general consensus in the scientific community is that the field of synthetic life merits further research for potential beneficial applications, so long as there is a good deal of safety precautions vigilantly employed.

Posted by Rebecca Sato