Posts Tagged ‘dna’

New Genetic Circuit Detects Cancerous Cells and Forces Them To Commit Suicide

A new DNA-based logic circuit can sense the signs of cancer, compute that a cell is cancerous, and then cause it to self-destruct, researchers say. The cell-level diagnostic system could be used for drug screening or perhaps for disease treatment, killing tumors while leaving healthy cells alone.

In principle, the circuit works like any other logic circuit: It analyzes multiple inputs and makes a decision. In this case, the circuit really consists of genes that can detect up to five cancer-specific molecules and their concentrations. When all five of those characteristics are present, the circuit makes a positive determination, and then it triggers cell death.

In a new study, researchers from MIT and ETH Zurich worked with HeLa cells, a prolific type of cervical cancer cell. They studied the cells’ microRNA, which regulates gene expression by destroying messenger RNA, the substance that brings the DNA blueprint to the rest of the cell. They eventually pinpointed one microRNA combo that was unique to HeLa cells. This is no small feat by itself — there are about 1,000 versions of miRNA in humans, according to MIT News. Each type of cancer has a unique miRNA profile.

Once they had the right combination, the researchers designed a synthetic gene which codes for a protein that promotes apoptosis, or programmed cell death. The special gene would turn on in the presence of miRNA levels that match the HeLa profile.

“The biocomputer combines the factors using logic operations such as AND and NOT, and only generates the required outcome, namely cell death, when the entire calculation with all the factors results in a logical TRUE value,” Yaakov Benenson, a professor of synthetic biology at ETH Zurich, said in a statement.

If the miRNA levels were too high or too low, the gene would not switch on, and the cell would not be killed. Healthy cells, which would also lack the HeLa profile, would be similarly left alone, the researchers said.

The next step would be to test this system in a living animal, but this will be difficult. Current methods use viruses or chemicals to bring foreign DNA inside cells, but these make permanent changes, which could have their own complications. So the method is still far from being usable for cancer treatment, researchers said.

Still, it is an important step toward building a single-cell-level diagnostic method, Benenson said. The research was published in today’s issue of Science.

[Eurekalert]

Blood Test Can Tell Fetus’s Sex at Just 7 Weeks

A simple blood test can determine a baby’s gender as early as seven weeks into pregnancy, a new study says — far earlier and far less invasive than other options. The test could conceivably help parents who are worried about gender-related diseases, but it could also allow people to wade into the morally murky waters of sex selection.

The test analyzes fetal DNA found in a mother’s blood, according to a report in the New York Times. If a Y chromosome is present, the mother is having a boy; if it’s not, it probably means the fetus is female (but could also mean that blood sample doesn’t contain fetal DNA). Researchers examined 57 studies of fetal DNA tests, spanning some 6,500 pregnancies. The results were published in the Journal of the American Medical Association.

This could be good news for parents whose offspring are at risk of rare gender-related genetic disorders, like Duchenne muscular dystrophy in boys or Turner syndrome in girls. Knowing fetal sex early on would help parents determine whether they need to undergo costly genetic testing. But it also raises questions about selective abortions of undesired genders. The tests are not sold in China or India, where female fetuses are selectively aborted. And at least one company that sells the tests in this country makes parents sign a waiver saying they are not using it for that purpose.

The tests have been available in the US for some time, but their reliability has been contested, sometimes in court. In one particularly sensational example, a pregnant mother was told she was having a boy, but an ultrasound later revealed she was carrying a girl. When she complained, the company told her they were certain “genetically you are having a male,” she told the Times — on the outside, it may look like a girl, but “we’re giving you the results on the inside.”

Given these uncertainties, doctors don’t prescribe the tests, but that could change now that they’ve been proven effective if used properly, the Times says.

The FDA does not regulate them, because they’re not used for a medical purpose, at least not officially. But the agency is studying the kits, the Times says.

In the meantime, the tests’ effectiveness means curious parents who don’t want to be surprised can start painting the nursery really, really early.

[New York Times]

New Fluorescent ‘Spinach’ Molecule Illuminates Inner Workings of RNA

Greens are good for you

The newest optical techniques are making cell biology a little clearer, but it’s still a murky business, watching cells work. A new technique that illuminates RNA — the builder of proteins, making copies according to DNA’s blueprint — is one way to shine a light on that process.

Researchers have been using green fluorescent protein for years, tagging molecules and cells to make them glow under certain conditions and when certain changes occur. Now scientists at Weill Cornell Medical School in New York have figured out how to make RNA molecules light up, so they can watch them at work.

Monitoring RNA could help biologists understand how and when the molecules move around in cells, in response to which signals. This could help answer questions about gene expression and about viruses, which use RNA instead of DNA as their genetic material.

Jeremy Paige and colleagues at Weill Cornell worked with derivatives of the green fluorescent protein molecule, called fluorophores, which are what make the molecule glow in certain light wavelengths. They looked for short RNA molecules that could bind to them, the team explains in a paper published today in Science.

They found a host of combinations across the visible spectrum, but just like with jellyfish protein, green was the best. A combination of RNA and fluorophore complexes nicknamed Spinach is just as bright as GFP, the researchers say. What’s more, it doesn’t bleach under microscopic light, and it makes molecules glow faster than regular GFP. They tested it with E. coli and watched bacterial colonies light up.

The method could be a simpler way to tag RNAs for a wide range of applications, the researchers say.

[Science]

UK Researchers Urge Rules Governing Creation and Use of Human-Animal Hybrids

A new regulatory group should be formed to oversee experiments that mix animal and human DNA, British researchers said Friday. While the experiments themselves don’t necessarily need stricter regulation, there are a few types of experiments that could “approach social and ethically sensitive areas,” so they should have an extra layer of scrutiny, the researchers said.

Although it sounds like something from science fiction, human-animal hybrids are actually very common — at least on a genetic, cellular level. In the past few weeks alone, we’ve seen mice engineered to express a human form of hemophilia, and cows engineered to produce milk with human characteristics. Human DNA is frequently inserted into mice to study cancer, and so on.

But some experiments are a little more ... bizarre, for lack of a better word. Like fertilizing human eggs in animals. Or experiments that would use human brain cells to alter animal brains. Or giving animals human-like speech or facial expressions.

While these types of experiments don’t seem likely, some researchers argue they could be valuable, the Associated Press reports. Injecting human brain cells into rat brains could help researchers study stroke treatments, for instance. Reuters points out that the world's first clinical trial using stem cell therapy in stroke patients was only possible after first testing human brain cells on rats.

“Where people begin to worry is when you get to the brain, to the germ (reproductive) cells, and to the sort of central features that help us recognize what is a person, like skin texture, facial shape and speech,” said Martin Bobrow, a professor of medical genetics at the University of Cambridge, in a news conference.

Bobrow led a working group of Britain’s Academy of Medical Sciences that examined creating animals with human facets.

Part of the controversy in the UK stemmed from plans three years ago to make human embryos with the nucleus hollowed out of cow eggs, the AP reports. The research was intended to make a new supply of stem cells that could be used to treat a wide range of diseases. The cells were 99.9 percent human and 0.1 percent other animal, the Guardian reported at the time.

Other countries should probably follow suit, and come up with their own regulatory mechanisms for overseeing such experiments, Bobrow said.

[via Associated Press]

Largest DNA-Based Computer Ever Built Can Calculate Square Roots

A test-tube circuit made of DNA-based logic gates can calculate the square root of numbers up to 15, using DNA replication and sequence binding to conduct computations. It’s excruciatingly slow — a calculation can take up to 10 hours — so organic laptops are not exactly in our near future. But the real breakthrough is in how this system can enable control of chemical systems.

Researchers at Caltech engineered the most complex biochemical circuit ever created from scratch, according to a new paper published today. The circuit uses DNA instead of electronic transistors to produce the on-off, and-or signals that allow a computer to conduct its calculations.

In a typical computer, transistors let a current of electrons flow in and out. The DNA computer instead uses pieces of short, single-stranded DNA or partially double-stranded DNA placed in a test tube of salt water. The strands stick out like tentacles from the DNA’s double helix, as a news release from Caltech explains. The DNA molecules collide in the water and bind together, producing and releasing offspring molecules. These act as the signals, like electrons in a traditional chip, and they travel among the DNA “gates,” connecting the circuit.

Pairs of gates can create and-or logic based on the output molecules observed, as Ars Technica explains it. (Check out Ars Technica's post for a more thorough explanation of how this works.)

The researchers, led by postdoctoral researcher Lulu Qian, can encode whatever DNA sequence they want, so they have full control over how the DNA strands interact.

Their largest computer was a 74-molecule, four-bit circuit that could compute the square root of any number up to 15, rounding down the answer to the nearest whole number. To get the answer, the researchers would monitor the concentration of output molecules in the test tube, using fluorescent tagging.

The process takes a long time, but speed is not the point — using this method, scientists could eventually engineer biochemical pathways that are capable of making decisions. This type of control over chemical reactions could be useful for anything from pharmaceuticals to industrial processes. Imagine DNA-based computer chips embedded in your skin, releasing drugs when the time is right, or a DNA computer that can study the concentration of certain molecules in a blood sample and quickly diagnose a disease.

The circuit can be scaled up to larger DNA computers, the researchers say. They can also be customized by adjusting the types of DNA used or reconfiguring the circuit.

“We want to make better and better biochemical circuits that can do more sophisticated tasks, driving molecular devices to act on their environment,” Qian said in a news release. The computer was described in a paper in today's issue of the journal Science.

[Eurekalert, ComputerWorld]

Chemists Design Method to Figure Out What Your Meat Ate

Foodies want to know everything about their animal-based dishes these days — where the meat came from, what it ate, what its name was. OK, maybe not that last part. But there is a big difference between industrial cattle farms and grass-fed meat — both in price and in nutritional considerations.

We’ve already seen how chemistry can help monitor the source of your meals, ensuring that you don’t eat endangered species. Now you can tell what your beef ate before it reached your plate.

A group of chemists from Ireland figured out a way to reconstruct the diet of cattle, determining whether they spent their days munching fresh pasture grasses rather than barley or silage. Frank J. Monahan and colleagues studied the proportions of stable isotopes of oxygen, nitrogen, hydrogen and sulfur found in the muscle tissue and tail hair of Irish beef cattle. They were able to determine what the animals primarily ate, and in some cases, could even figure out where the animals came from.

Certain diets yielded a distinctive signature, the researchers report in the Journal of Agricultural and Food Chemistry. They couldn’t tell between animals that ate from a pasture and those that ate grass silage, but there were clear differences between animals that ate pasture grass and those that ate concentrated food products. Using hair and tail samples, they could even follow changes in an animal’s diet over the course of its lifetime. The researchers could tell whether a steer had switched from a grass diet to a corn-based diet near the end of its life, for instance.

Monitoring animals’ tail hair yielded such precise information about diet that it could be used to monitor farms’ production practices, the authors say.

Stable isotope ratios have also been used to determine the source of bottled drinks, and figure out where people have been based on chemicals left behind in their hair.

Speaking of soft drinks, chemists also announced this week that they're using protein analysis to test for kola nuts, a pricey ingredient found in natural cola drinks. Drinks containing the kola nut had the signature of plant proteins, while Coca Cola — which does not claim to use the kola nut — did not.

Testing methods like these could give consumers assurances that they really are getting what they pay for.

[Eurekalert]

FYI: What’s the Point of Sex?

This may seem obvious. But in evolutionary terms, the benefits of sexual reproduction are not immediately clear. Male rhinoceros beetles grow huge, unwieldy horns half the length of their body that they use to fight for females. Ribbon-tailed birds of paradise produce outlandish plumage to attract a mate. Darwin was bothered by such traits, since his theory of evolution couldn’t completely explain them (“The sight of a feather in a peacock’s tail, whenever I gaze at it, makes me feel sick!” he wrote to a friend). 

Moreover, sex allows an unrelated, possibly inferior partner to insert half a genome into the next generation. So why is sex nearly universal across animals, plants and fungi? Shouldn’t natural selection favor animals that forgo draining displays and genetic roulette and simply clone themselves?

Yes and no. Many animals do clone themselves; certain sea anemones can bud identical twins from the sides of their bodies. Aphids, bees and ants can reproduce asexually. Virgin births sometimes occur among hammerhead sharks, turkeys, boa constrictors and komodo dragons. But nearly all animals engage in sex at some point in their lives. Biologists say that the benefits of sex come from the genetic rearrangements that occur during meiosis, the special cell division that produces eggs and sperm. During meiosis, combinations of the parents’ genes are broken up and reconfigured into novel arrangements in the resulting sperm and egg cells, creating new gene combinations that might be advantageous. 

One animal, however, has done just fine without any sex at all. Bdelloid rotifers can be found in most freshwater ponds, measure a few tenths of a millimeter long, contain only about 1,000 cells, and have been chaste for roughly 80 million years. The nearly 400 described species of bdelloids prove that the group is respectably diverse, yet no one has ever seen a male. Bdelloids lay unfertilized eggs that grow to be fully fertile daughters. What’s the secret?

Harvard University biology professor Matthew Meselson and his lab have spent the past several years investigating bdelloids’ molecular genetics. By exposing bdelloids to extremely high levels of ionizing radiation (a treatment that causes hundreds of physical breaks in DNA strands), one of Meselson’s former graduate students, Eugene Gladyshev, showed that bdelloids can completely rebuild their genomes—an unprecedented feat among animals.

Recently, Meselson and Gladyshev made an even more amazing discovery: Bdelloids have foreign DNA from bacteria and fungi in their chromosomes, which is a great way to maintain genetic diversity. As for the rest of us, we’re stuck with sex.

Have a science question you've always wondered about? Email fyi@popsci.com


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