Tag Archive: DNA


A Rare Genetic Mutation in These Siblings Makes Them Immune to Viruses

Viruses are incompetent but smart little things. Unable to make proteins on their own, they hijack ours for their own nefarious purposes. But what if we gave the viruses broken proteins? An incredibly rare genetic disorder in a brother and sister pair does exactly that, making them immune to many classes of viruses—and suggesting new possibilities for antiviral treatments.

The immunity to viruses for these siblings, however, comes at a cost. Their cases, reported recently in the New England Journal of Medicine, are only the second and third ever described of this rare genetic disorder. The first was in a baby who died at 74 days. The 11-year-old boy and 6-year-old girl in this report have suffered developmental delays, hearing loss, fragile bones, and a weakened immune system. That makes it all the more remarkable that they rarely got ear infections or the flu.

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Scientists in Canada have made DNA cubes that are programmed to unzip and reveal molecules locked inside them in response to a carefully chosen trigger. Hanadi Sleiman and colleagues at McGill University and the Jewish General Hospital in Montreal, designed the cubes to release the drug cargo they might be carrying only in diseased cells and not normal cells.

‘In the future, we would like to use our DNA cubes in the treatment of cancer and other diseases with a genetic component,’ says Sleiman. The cube opens into a flat assembly when a specific RNA sequence, in this case a gene product that is unique to prostate cancer cells, binds to two single-stranded DNA overhangs on the corners of the cube, disrupting the hydrogen-bonds that maintain the cube’s shape. Sleiman says it would be easy to change the sequence to which the cube responds and since the cube has two overhangs, ‘it would also be possible to make a cube that responds to two different triggers.’

The DNA cube was also modified with hydrophobic and hydrophilic chains to modulate its cellular uptake and prevent enzymatic degradation.

‘Compared with previous DNA origami-based designs the present system does not rely on the use of M13 [bacteriophage] DNA and can therefore be applied to many targets,’ comments Hiroshi Sugiyama, a DNA nanotechnology expert at Kyoto University in Japan.

Laboratory mouse

Australian and US researchers have developed a compound which reverses muscle ageing in mice, saying it could be one of the keys to reversing ageing in humans. When used in trials, the compound gave mice more energy, toned their muscles, reduced inflammation, and led to big improvements in insulin resistance.

Scientists say it actually reversed the ageing process, not just slowing it down, and say that for humans the effect would be similar to a 60-year-old feeling like a 20-year-old. And they say human trials could start within the year.

“I’ve been studying ageing at the molecular level now for nearly 20 years and I didn’t think I’d see a day when ageing could be reversed. I thought we’d be lucky to slow it down a little bit,” University of New South Wales geneticist Professor David Sinclair said.

“The mice had more energy, their muscles were as though they’d be exercising and it was able to mimic the benefits of diet and exercise just within a week.”

Professor Sinclair led the study from his base at Harvard Medical School in the US.

“We think that should be able to keep people healthier for longer and keep them from getting diseases of ageing,” he said.

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This second code contains information that changes how scientists read the instructions contained in DNA and interpret mutations to make sense of health and disease.

A research team led by Dr. John Stamatoyannopoulos, University of Washington associate professor of genome sciences and of medicine, made the discovery. The findings are reported in the Dec. 13 issue of Science. The work is part of the Encyclopedia of DNA Elements Project, also known as ENCODE. The National Human Genome Research Institute funded the multi-year, international effort. ENCODE aims to discover where and how the directions for biological functions are stored in the human genome.

Since the genetic code was deciphered in the 1960s, scientists have assumed that it was used exclusively to write information about proteins. UW scientists were stunned to discover that genomes use the genetic code to write two separate languages. One describes how proteins are made, and the other instructs the cell on how genes are controlled. One language is written on top of the other, which is why the second language remained hidden for so long.

“For over 40 years we have assumed that DNA changes affecting the genetic code solely impact how proteins are made,” said Stamatoyannopoulos. “Now we know that this basic assumption about reading the human genome missed half of the picture. These new findings highlight that DNA is an incredibly powerful information storage device, which nature has fully exploited in unexpected ways.”

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Sima de los Huesos remains

That’s the verdict cast by human evolution experts on an analysis in Nature journal of the oldest human genetic material ever sequenced.

The femur comes from the famed “Pit of Bones” site in Spain, which gave up the remains of at least 28 ancient people.

But the results are perplexing, raising more questions than answers about our increasingly complex family tree.

The early human remains from the cave site near the northern Spanish city of Burgos have been painstakingly excavated and pieced together over the course of more than two decades. It has yielded one of the richest assemblages of human bones from this stage of human evolution, in a time called the Middle Pleistocene.

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Scientists Rewrite an Entire Genome and Add a Healthy Twist

Scientists from Yale and Harvard have recoded the entire genome of an organism and improved a bacterium’s ability to resist viruses, a dramatic demonstration of the potential of rewriting an organism’s genetic code.

“This is the first time the genetic code has been fundamentally changed,” said Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale and co-senior author of the research published October 18 in the journal Science. “Creating an organism with a new genetic code has allowed us to expand the scope of biological function in a number of powerful ways.”

The creation of a genomically recoded organism raises the possibility that researchers might be able to retool nature and create potent new forms of proteins to accomplish a myriad purposes — from combating disease to generating new classes of materials.

The research — headed by Isaacs and co-author George Church of Harvard Medical School — is a product of years of studies in the emerging field of synthetic biology, which seeks to re-design natural biological systems for useful purposes.

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Scientists have studied the behavior of complex biological molecules such as DNA for decades. Now they are moving to being able to control that behavior in test tubes and inside cells.

Last month, a team led at the University of Washington announced they had devised and successfully tested a programming language that can guide the assembly of synthetic DNA molecules into a circuit that can perform a task, just as a software developer would write code to send commands to a computer.

Chemists have always used mathematical models to study how molecules behave in mixtures. “Instead of thinking of this as a descriptive language that allows you to understand the chemistry, we said, we’re going to create a prescriptive language that allows you to program something,” says Georg Seelig, an assistant professor of electrical engineering and computer science at the school.

While there’s no killer app anywhere near ready yet, possible future uses for being able to design and assemble DNA to perform a specified function are wide-ranging. Seelig imagines programming molecules to act as embedded sensors inside cells that could respond to changing conditions, just as internal electronics guide the operation of automobiles or home appliances.

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Scientists will soon be able to design and print simple organisms using biological 3D printers says J. Craig Venter, the scientist who led the private-sector’s mapping of the human genome.

Venter predicts that new methods of digital design and manufacture will provide the next revolution in genetic with synthetic cells and organism tailor-made to tackle humanity’s problems: a toolkit of sequenced genes will be used to create disease-resistant animals; higher yielding crops; and drugs that extend human life and boost our brain power.

These ideas have been outlined in Venter’s latest book ‘Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life’, in which the geneticists asks the age-old question ‘what is life?’ before detailing the history – and future – of creating the stuff from scratch.

For Venter life can be reduced to “protein robots” and “DNA machines” but he also believes that technology will unlock far more exotic opportunities for creating life. The title of the publication refers to the idea that we may be able to transmit DNA sequences found on Mars back to Earth (at the speed of light) to be replicated at home by biological printers.

“I am confident that life once thrived on Mars and may well still exist there today,” writes Venter. “The day is not far off when we will be able to send a robotically controlled genome-sequencing unit in a probe to other planets to read the DNA sequence of any alien microbe life that may be there.”

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Detecting DNA in space

Detecting DNA in space

If there is life on Mars, it’s not too farfetched to believe that such Martian species may share genetic roots with life on Earth.

More than 3.5 billion years ago, a blitz of meteors ricocheted around the solar system, passing material between the two fledgling planets. This galactic game of pingpong may have left bits of Earth on Mars, and vice versa, creating a shared genetic ancestry between the two planets.

Such a theory holds great appeal for Christopher Carr, a research scientist in MIT’s Department of Earth, Atmospheric and Planetary Sciences. Working with Gary Ruvkun at Massachusetts General Hospital (MGH) and Maria Zuber, the E.A. Griswold Professor of Geophysics and MIT’s vice president for research, Carr is building a DNA sequencer that he hopes will one day be sent to Mars, where it can analyze soil and ice samples for traces of DNA and other genetic material.

Now in a step toward that goal, Carr and colleagues at MIT, Harvard University and MGH have exposed the heart of their tool — a DNA-sequencing microchip — to radiation doses similar to those that might be expected during a robotic expedition to Mars. After exposure to such radiation — including protons and heavy ions of oxygen and iron — the microchip analyzed a test strain of E. coli, successfully identifying its genetic sequence.

Carr says the group’s results show the microchip can survive up to two years in space — long enough to reach Mars and gather data there for a year and a half.

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This illustration shows Tribolium castaneum telomerase catalytic subunit, TERT (Emskorda / CC BY-SA 3.0)

The human body consists of fifty trillion cells, and each cell has 46 chromosomes which are the structures in the nucleus containing our hereditary material, the DNA. The ends of all chromosomes are protected by so-called telomeres.

The telomeres serve to protect the chromosomes in much the same way as the plastic sheath on the end of a shoelace. But each time a cell divides, the telomeres become a little bit shorter and eventually end up being too short to protect the chromosomes.

Each cell has a ‘multi-ride ticket,’ and each time the cell divides, telomeres will use up one ride. Once there are no more rides left, the cell will not divide any more, and will ‘retire.’ But some special cells in the body can activate telomerase, which again can elongate the telomeres.

Sex cells, or other stem cells, which must be able to divide more than normal cells, have this feature. Unfortunately, cancer cells have discovered the trick, and it is known that they also produce telomerase and thus keep themselves artificially young. The telomerase gene therefore plays an important role in cancer biology, and it is precisely by identifying cancer genes that the researchers imagine that you can improve the identification rate and the treatment.

“We have discovered that differences in the telomeric gene are associated both with the risk of various cancers and with the length of the telomeres. The surprising finding was that the variants that caused the diseases were not the same as the ones which changed the length of the telomeres. This suggests that telomerase plays a far more complex role than previously assumed,” said Dr Stig Bojesen from the University of Copenhagen, Denmark, first author of a paper published in Nature Genetics.

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The Genomic Instability Group led by researcher Óscar Fernández-Capetillo at the Spanish National Cancer Research Centre (CNIO), has for the first time obtained a panoramic photo of the proteins that take part in human DNA division, a process known as replication.

The research article, published today in the journal Cell Reports, is the result of a collaborative study in which other CNIO groups have also participated, including the Proteomics Unit led by Javier Muñoz and the DNA Replication Group led by Juan Méndez.

DNA replication is the chemical process that sustains cell division, and thus one of the biological mechanisms targeted by most chemotherapeutic agents in order to destroy tumour cells.

To date, multiple independent molecular studies carried out over the last decades have given a general idea of the proteins involved in the replication process. “We suspected that there might be several dozen proteins that control this process meticulously, thus ensuring the correct duplication of our genome as an indispensible step prior to cell division,” explains Fernández-Capetillo.

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Fluorescent dyes track the presence of the RNA molecules and the genes they  affect in the developing mouse brain.

Specific DNA once dismissed as junk plays an important role in brain development and might be involved in several devastating neurological diseases, UC San Francisco scientists have found.

Their discovery in mice is likely to further fuel a recent scramble by researchers to identify roles for long-neglected bits of DNA within the genomes of mice and humans alike.

While researchers have been busy exploring the roles of proteins encoded by the genes identified in various genome projects, most DNA is not in genes. This so-called junk DNA has largely been pushed aside and neglected in the wake of genomic gene discoveries, the UCSF scientists said.

In their own research, the UCSF team studies molecules called long noncoding RNA (lncRNA, often pronounced as “link” RNA), which are made from DNA templates in the same way as RNA from genes.

“The function of these mysterious RNA molecules in the brain is only beginning to be discovered,” said Daniel Lim, MD, PhD, assistant professor of neurological surgery, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, and the senior author of the study, published online April 11 in the journal Cell Stem Cell.

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DNA Double Helix

Pretty much anything can be a computer, if it can compute logical functions, store data, and transmit information — even living cells. A team at Stanford University has accomplished one of the the final tasks necessary to turn cells into working computers: They’ve created a biological transistor, called a transcriptor, that uses DNA and RNA instead of electrons and responds to logical functions.

Drew Endy, an assistant professor of bioengineering, has previously made other vital contributions to biocomputing. Last year, his lab developed a “biological Internet” that can transmit genetic information between cells, as well as a rewritable data storage system for DNA.

Building a system with logic gates that can compute true-false answers from biochemical information is the third component in creating a biological computer.

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The term “survival of the fittest” refers to natural selection in biological systems, but Darwin’s theory may apply more broadly than that. New research from the U.S. Department of Energy’s Brookhaven National Laboratory shows that this evolutionary theory also applies to technological systems.

Computational biologist Sergei Maslov of Brookhaven National Laboratory worked with graduate student Tin Yau Pang from Stony Brook University to compare the frequency with which components “survive” in two complex systems: bacterial genomes and operating systems on Linux computers.

Their work is published in the Proceedings of the National Academy of Sciences. Maslov and Pang set out to determine not only why some specialized genes or computer programs are very common while others are fairly rare, but to see how many components in any system are so important that they can’t be eliminated. “If a bacteria genome doesn’t have a particular gene, it will be dead on arrival,” Maslov said. “How many of those genes are there? The same goes for large software systems. They have multiple components that work together and the systems require just the right components working together to thrive.’”

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PSA: DNA

Public Service Announcement

Synthetic biologists have developed DNA modules that perform logic operations in living cells. These ‘genetic circuits’ could be used to track key moments in a cell’s life or, at the flick of a chemical switch, change a cell’s fate, the researchers say. Their results are described this week in Nature Biotechnology.

Synthetic biology seeks to bring concepts from electronic engineering to cell biology, treating gene functions as components in a circuit. To that end, researchers at the Massachusetts Institute of Technology (MIT) in Cambridge have devised a set of simple genetic modules that respond to inputs much like the Boolean logic gates used in computers.

“These developments will more readily enable one to create programmable cells with decision-making capabilities for a variety of applications,” says James Collins, a synthetic biologist at Boston University in Massachusetts who was not involved in the study.

Collins developed the genetic ‘toggle switch’ that helped to kick-start the field of synthetic biology more than a decade ago. A wide range of computational circuits for cells have been developed since, including a simple counter that Collins and his team devised in 2009.

But “to make this a really rigorous engineering discipline, we need to move towards frameworks that allow you to program cells in a more scalable fashion,” says Timothy Lu, a synthetic biologist at MIT who led the latest research. “We wanted to show you can assemble a bunch of simple parts in a very easy fashion to give you many types of logical functions.”

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DNA tags label rioters and other criminals so cops can find them “at a less confrontational time for officers.”

DNA Gun In Action

Riots are a tough nut for law enforcement in part because of the sheer number of people involved–it’s impossible to stop and arrest every person involved in a skirmish. That’s why cops have some pretty high-tech methods for catching suspects, from facial recognition software to debilitating sonic cannons. But none is as bizarre as this new DNA gun from a UK security firm.

The SelectaDNA High Velocity System works like it sounds–it shoots people with pellets containing a unique DNA fingerprint. Unlike rubber-pellet guns, Tasers or tear gas canisters, the technology does not deter or disable the suspect–he or she can get away seemingly unscathed. But later, authorities can track down the suspect and arrest him or her “at a less confrontational time for officers,” according to the company. Portable readers equipped with ultraviolet light scanners would be able to verify the synthetic DNA.

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ll 154 Shakespeare sonnets were spelled out in DNA to demonstrate the vast potential of genetic data storage.

William Shakespeare

His words have touched the lovelorn and been pored over by brooding teenagers for more than four hundred years, but now some of the most romantic poems ever penned have been written into the code of life.

The entire collection of Shakespeare’s 154 sonnets has been spelled out in DNA by scientists in Cambridge to demonstrate the vast potential of genetic storage. Huge quantities of information could be written into specks of DNA and archived for tens of thousands of years, the researchers claim.

Alongside the Bard’s sonnets, the scientists made strands of DNA that stored part of an audio file of Martin Luther King’s 1963 speech “I have a dream”, and the seminal research paper that first described the double helical nature of DNA by Francis Crick and James Watson, a decade earlier.

Written in DNA, one of Shakespeare’s sonnets weighs 0.3 millionths of a millionth of a gram. One gram of DNA could hold as much information as more than a million CDs, the researchers said.

Nick Goldman and Ewan Birney at the European Bioinformatics Institute in Hinxton, near Cambridge, came up with the idea in a pub in Hamburg. They wondered what alternatives might exist to the expensive hard disks and magnetic tapes used to store the growing datasets that are becoming ever more common in biology.

They knew that DNA was an incredibly efficient and compact way to store information, and set about devising a way to turn the molecules into digital memory: capable of encoding the 1s and 0s used to store words, images, music and video on computers.

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A team of Scottish researchers say that they have made a breakthrough discovery, locating the moment in evolutionary history when intelligence and the ability to reason first appeared in our earliest ancestors. They also say that the root cause of many brain disorders can also be traced back to the same genetic events.

According to Seth Grant, the lead researcher on the study and a professor of molecular neuroscience at University of Edinburgh: “One of the greatest scientific problems is to explain how intelligence and complex behaviours arose during evolution.”

Grant and his colleagues say this happened around 500 million years ago as a result of a sudden increase in the number of brain genes possessed by our early invertebrate ancestors. The researchers say that these simple ocean-dwelling animals experienced a ‘genetic accident’ that resulted in an unintended multiplication in the number of brain genes that they possessed. In the millions of years that followed, these extra intelligence genes provided survival benefits to the animals that inherited them and gave rise to increasingly sophisticated behaviors. In humans, these abilities reached their peak with our unique abilities to analyze situations, understand abstract concepts and learn complicated skills.

The study results, which have been published as two papers in the journal Nature Neuroscience, also point to a direct link between the evolution of complex behavior and the origins of a number of brain disorders. The scientists say that the same genes that gave us our enhanced cognitive abilities are also to blame for a variety of common brain diseases.

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PSA: DNA

Public Service Announcement: DNA

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The DNA Replication Complex, an assembly of proteins that synthesizes new DNA before cell division.  It consists of Helicase, Primase, Single-strand binding proteins, and DNA polymerase III.  Because DNA strands can only be copied in one direction, the complex must pull out loops of one strand and replicate it in fragments.  At this moment there are hundreds of trillions of these molecular machines in constant activity within your body.

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