Hidden Genetic Code

A hidden genetic code for better designer genes:

 

A hidden genetic code for better designer genes

A hidden genetic code for better designer genes

 

Scientists routinely seek to reprogram bacteria to produce proteins for drugs, biofuels and more, but they have struggled to get those bugs to follow orders. But a hidden feature of the genetic code, it turns out, could get bugs with the program. The feature controls how much of the desired protein bacteria produce, a team from the Wyss Institute for Biologically Inspired Engineering at Harvard University reported in the September 26 online issue of Science.

The findings could be a boon for biotechnologists, and they could help synthetic biologists reprogram bacteria to make new drugs and biological devices.

By combining high-speed “next-generation” DNA sequencing and DNA synthesis technologies, Sri Kosuri, Ph.D., a Wyss Institute staff scientist, George Church, Ph.D., a core faculty member at the Wyss Institute and professor of genetics at Harvard Medical School, and Daniel Goodman, a Wyss Institute graduate research fellow, found that using more rare words, or codons, near the start of a gene removes roadblocks to protein production.

“Now that we understand how rare codons control gene expression, we can better predict how to synthesize genes that make enzymes, drugs, or whatever you want to make in a cell,” Kosuri said.

To produce a protein, a cell must first make working copies of the gene encoding it. These copies, called messenger RNA (mRNA), consist of a specific string of words, or codons. Each codon represents one of the 20 different amino acids that cells use to assemble proteins. But since the cell uses 61 codons to represent 20 amino acids, many codons have synonyms that represent the same amino acid.

In bacteria, as in books, some words are used more often than others, and molecular biologists have noticed over the last few years that rare codons appear more frequently near the start of a gene. What’s more, genes whose opening sequences have more rare codons produce more protein than genes whose opening sequences do not.

No one knew for sure why rare codons had these effects, but many biologists suspected that they function as a highway on-ramp for ribosomes, the molecular machines that build proteins. According to this idea, called the codon ramp hypothesis, ribosomes wait on the on-ramp, then accelerate slowly along the mRNA highway, allowing the cell to make proteins with all deliberate speed. But without the on-ramp, the ribosomes gun it down the mRNA highway, then collide like bumper cars, causing traffic accidents that slow protein production. Other biologists suspected rare codons acted via different mechanisms. These include mRNA folding, which could create roadblocks for ribosomes that block the highway and slow protein production.

To see which ideas were correct, the three researchers used a high-speed, multiplexed method that they’d reported in August in The Proceedings of the National Academy of Sciences.

First, they tested how well rare codons activated genes by mass-producing 14,000 snippets of DNA with either common or rare codons; splicing them near the start of a gene that makes cells glow green, and inserting each of those hybrid genes into different bacteria. Then they grew those bugs, sorted them into bins based on how intensely they glowed, and sequenced the snippets to look for rare codons.

They found that genes that opened with rare codons consistently made more protein, and a single codon change could spur cells to make 60 times more protein.

“That’s a big deal for the cell, especially if you want to pump out a lot of the protein you’re making,” Goodman said.

The results were also consistent with the codon-ramp hypothesis, which predicts that rare codons themselves, rather than folded mRNA, slow protein production. But the researchers also found that the more mRNA folded, the less of the corresponding protein it produced — a result that undermined the hypothesis.

To put the hypothesis to a definitive test, the Wyss team made and tested more than 14,000 mRNAs – including some with rare codons that didn’t fold well, and others that folded well but had no rare codons. By quickly measuring protein production from each mRNA and analyzing the results statistically, they could separate the two effects.

The results showed clearly that RNA folding, not rare codons, controlled protein production, and that scientists can increase protein production by altering folding, Goodman said.

The new method could help resolve other thorny debates in molecular biology. “The combination of high-throughput synthesis and next-gen sequencing allows us to answer big, complicated questions that were previously impossible to tease apart,” Church said.

“These findings on codon use could help scientists engineer bacteria more precisely than ever before, which is tremendous in itself, and they provide a way to greatly increase the efficiency of microbial manufacturing, which could have huge commercial value as well,” said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. “They also underscore the incredible value of the new automated technologies that have emerged from the Synthetic Biology Platform that George leads, which enable us to synthesize and analyze genes more rapidly than ever before.”

Government Scanners Instantly Know Everything About You

 Hidden Government Scanners Will Instantly Know Everything About You From 164 Feet Away:

Hidden Government Scanners Will Instantly Know Everything About You From 164 Feet Away

Hidden Government Scanners Will Instantly Know Everything About You From 164 Feet Away

Within the next year or two, the U.S. Department of Homeland Security will instantly know everything about your body, clothes, and luggage with a new laser-based molecular scanner fired from 164 feet (50 meters) away. From traces of drugs or gun powder on your clothes to what you had for breakfast to the adrenaline level in your body. According to the undersecretary for science and technology by the Department of Homeland Security, you might start seeing [these scanners] in airports as soon as 2013.  And, since it’s extremely portable, will this technology extend beyond the airport or border crossings and into police cars, with officers looking for people on the street with increased levels of adrenaline in their system to detain in order to prevent potential violent outbursts? And will your car be scanned at stoplights for any trace amounts of suspicious substances? Would all this information be recorded anywhere?

Green products contain hidden toxic chemicals

Tests Find Toxics in Broad Array of Consumer Products:

 

Toxic chemicals linked to the rising rates of endocrine disruption related disease were found in a broad array of consumer products and reported in a peer reviewed article in Environmental Health Perspectives on March 8. The Silent Spring Institute tested 213 consumer products, including cleaning products, cosmetics, sunscreens, shower curtains, air fresheners, drier sheets, and other household goods made by Colgate, Unilever, S.C. Johnson, Johnson and Johnson, Procter & Gamble, Seventh Generation, and Ecover among other manufacturers.  “These test results show that both conventional and so-called green products contain hidden toxic chemicals that are not on product labels—so consumers have no way of avoiding them,” says Alexandra Scranton from Women’s Voices for the Earth, who recently conducted their own tests for hidden toxic chemicals in 20 top brand-name cleaning products. “Companies need to phase out these harmful chemicals, and we need a policy that standardizes labeling guidelines for cleaning products, so companies can’t keep these toxic chemicals a secret.”  Environmental health advocates across the nation see this new study as confirmation that ubiquitous chemical exposure is playing a factor in adverse health impacts.  “Silent Spring used Battelle Labs in Ohio, and they found 55 chemicals associated with endocrine disruption or with asthma, including parabens, BPA, triclosan, Alkylphenols, cyclosiloxanes,” said Martha Arguello, with Physicians for Social Responsibility—Los Angeles. “It is not good science to assume that cumulative exposure to these chemicals is safe.”  “This new study found PVC products, including a pillow protector and shower curtain, contained high levels of the toxic phthalate DEHP,” said Mike Schade from the Center for Health, Environment & Justice. “Phthalates have been banned in toys, but are widespread in many PVC products children coming in contact with in schools and even at home. Phthalates have been linked to asthma, adverse impacts on brain development, and reproductive health problems in baby boys. Thankfully, there are safer cost-effective alternatives to phthalate-laden PVC products for our schools and homes.”  “Many  products are targeted to women of color who suffer from high health disparities that can be linked directly to the endocrine disruptors found in these products. We can only hope that studies like this one inspire better policies and regulations of these dangerous chemicals,” said Janette Robinson-Flint from Black Women for Wellness. “Mother’s shouldn’t have to be a biochemist to protect themselves and their families from toxic chemicals in everyday products.” “We know many folks have tested positive for BPA and Triclosan in our human Biomonitoring studies,” said Sharyle Patton, director of the Biomonitoring Resource Center at Commonweal. “One has to wonder if rising rates of  associated health problems  are linked to these exposures.”  Caroline Cox, research director, Center for Environmental Health, said, “These unnecessary, untested and unlabeled chemicals in dozens of everyday products threaten our children’s and families’ health. It’s past time for federal action that calls for evaluating chemicals for safety before they end up contaminating our homes and our bodies.”  “This is another example of the failure of federal law to protect workers and consumers,” said Sarah Doll from SAFER States. “States have been acting to protect consumers from toxic chemicals in products for years now, and will continue to move on these issues in the absence of federal reform.”  The products were tested in 2008, and the study authors acknowledge that product samples can vary and that some formulations may have changed.