Mice made from induced stem cells

Technical feat shows that the different route to stem cells can indeed make a full mammal body.

David Cyranoski

Two teams of Chinese researchers have created live mice from induced pluripotent stem (iPS) cells, answering a lingering question about the developmental potential of the cells.

Since Shinya Yamanaka of Kyoto University in Japan created the first iPS cells¹ in 2006, researchers have wondered whether they could generate an entire mammalian body from iPS cells, as they have from true embryonic stem cells. Experiments reported online this week in Nature ² and in Cell Stem Cell ³ suggest that, at least for mice, the answer is yes.

For the first study, animal cloners Qi Zhou of the Institute of Zoology in Beijing and Fanyi Zeng of Shanghai Jiao Tong University started by creating iPS cells the same way as Yamanaka, by using viral vectors to introduce four genes into mouse fibroblast cells. The researchers hoped that the introduced factors would 'reprogram' the cells so that they could differentiate into any type of cell in the body.

To check whether the reprogramming had worked, Zhou and Zeng first carried out a standard set of tests, including analysing whether their iPS cells had the same surface markers as embryonic stem cells. Going a step further, they then created a 'tetraploid' embryo by fusing two cells of an early-stage fertilized embryo. A tetraploid embryo develops a placenta and other cells necessary for development, but not the embryonic cells that would become the body. It is, in essence, a car without a driver.

When implanted into these embryos, the iPS cells began to steer development. The developing embryo was transferred to a surrogate mother, and 20 days later a mouse was born. It was black, like the mice used to create the iPS cells and unlike the white mice used to create the tetraploid embryo. DNA tests confirmed the mouse, named Xiao Xiao or 'Tiny', had arisen from the iPS cells.

Rudolf Jaenisch, a cloning expert at the Massachusetts Institute of Technology in Cambridge, had tried to do the same experiment in 2007, but didn't succeed in getting beyond late-stage embryos⁴. "There were two possible explanations" for his team's failure, he says. "Either iPS cells aren't pluripotent so it was impossible, or we just hadn't tried hard enough. The first would have been more interesting, but I assumed it was the second explanation."

The Chinese team tried harder, tweaking the culture medium and analysing 250 developing embryos before getting their first mouse.

In the paper, the team reports 27 live births. With their best cell line and optimal recipe, they were able to get 22 live births from 624 injected embryos, a success rate of 3.5%.

Zeng says, however, that the mice seem to have a high death rate, with some dying after just two days, and others displaying physical abnormalities, details of which the team would not reveal. But some of their mice passed one of the most fundamental tests of health: all 12 mice that were mated produced offspring, and the offspring showed no abnormalities. The team says it now has hundreds of second-generation, and more than 100 third-generation, mice. The team found no tumours in the mice, although they have not systematically looked for them.

The leader of the second team, Shaorong Gao of the National Institute of Biological Sciences in Beijing, also credits persistence for success. His group, which used the same basic technique as Zeng and Zhou, transferred iPS cells to 187 tetraploid complementation embryos to get just two live births (a 1.1% efficiency rate), although one died in infancy. "The chance for generating such a cell line is rare but we tried very hard," he says. Gao's team is now trying to mate its surviving mouse.

Both groups are now trying to understand what differences between iPS cells and embryonic stem cells might explain the abnormalities, high death rates, low efficiency rates and the fact that most iPS cell lines don't seem to work in making mice. Zeng and Zhou found, for one thing, that timing was important: cells that formed iPS cell colonies quickly — after 14 days — were successful, whereas those that formed colonies after 20 or 36 days did not work. Gao suggests that "aberrant reprogramming" might be to blame, at least for the low efficiency rates.

Such mouse studies should help researchers to understand fundamental differences between human embryonic stem cells and iPS cells as well. Earlier this month, researchers at the University of California, Los Angeles, reported that human iPS cells that passed conventional pluripotency tests differed in gene expression from human embryonic stem cells⁵. "iPS cells might do things better or worse than embryonic stem cells," says team member Kathrin Plath. "I don't think we know the answer at this point." Because the tetraploid work cannot be done with human embryos, the Chinese studies can't say much about clinical applications of pluripotent cell lines, adds her colleague William Lowry.

Zhou and Zeng are pursuing several new avenues, including comparing the iPS mice with mice cloned with conventional techniques, and working to prove that the same experiment can be done with adult mice. (The fibroblasts used to create iPS cells in both studies came from late-stage embryos.)

This would essentially be a new way to clone adult mammals — reprogramming DNA from an adult and generating a genetically identical individual. As a potentially easier method that produces fewer abnormalities than conventional cloning, it might evoke interest among mavericks as a tool for human cloning. China recently strengthened its law prohibiting such cloning⁶.

Zhou says he hopes that researchers will take advantage of the technology as "an important model for understanding reprogramming". He adds: "It is not intended to be a first step towards using iPS cells to create a human being."

References:

1. Takahashi, K. & Yamanaka, S. Cell 126, 663-676 (2006). | Article | PubMed | ISI | ChemPort |
2. Zhao, X.-Y. et al. Nature advance online publication doi:10.1038/nature08267 (2009).
3. Kang, L. et al. Cell Stem Cell doi:10.1016/j.stem.2009.07.001 (2009).
4. Wernig, M. et al. Nature 448, 318-324 (2007). | Article | PubMed | ISI | ChemPort |
5. Chin, M. H. et al. Cell Stem Cell 5, 111-123 (2009). | Article | PubMed | ChemPort |
6. Cyranoski, D. Nature 459, 146-147 (2009). | Article | PubMed | ChemPort |

Brain Researchers Open Door to Editing Memory

By BENEDICT CAREY

Suppose scientists could erase certain memories by tinkering with a single substance in the brain. Could make you forget a chronic fear, a traumatic loss, even a bad habit.

Researchers in Brooklyn have recently accomplished comparable feats, with a single dose of an experimental drug delivered to areas of the brain critical for holding specific types of memory, like emotional associations, spatial knowledge or motor skills.

The drug blocks the activity of a substance that the brain apparently needs to retain much of its learned information. And if enhanced, the substance could help ward off dementias and other memory problems.

So far, the research has been done only on animals. But scientists say this memory system is likely to work almost identically in people.

The discovery of such an apparently critical memory molecule, and its many potential uses, are part of the buzz surrounding a field that, in just the past few years, has made the seemingly impossible suddenly probable: neuroscience, the study of the brain.

“If this molecule is as important as it appears to be, you can see the possible implications,” said Dr. Todd C. Sacktor, a 52-year-old neuroscientist who leads the team at the SUNY Downstate Medical Center, in Brooklyn, which demonstrated its effect on memory. “For trauma. For addiction, which is a learned behavior. Ultimately for improving memory and learning.”

Artists and writers have led the exploration of identity, consciousness and memory for centuries. Yet even as scientists sent men to the moon and spacecraft to Saturn and submarines to the ocean floor, the instrument responsible for such feats, the human mind, remained almost entirely dark, a vast and mostly uncharted universe as mysterious as the New World was to explorers of the past.

Now neuroscience, a field that barely existed a generation ago, is racing ahead, attracting billions of dollars in new financing and throngs of researchers. The National Institutes of Health last year spent $5.2 billion, nearly 20 percent of its total budget, on brain-related projects, according to the Society for Neuroscience.

Endowments like the Wellcome Trust and the Kavli Foundation have poured in hundreds of millions of dollars more, establishing institutes at universities around the world, including Columbia and Yale.

The influx of money, talent and technology means that scientists are at last finding real answers about the brain — and raising questions, both scientific and ethical, more quickly than anyone can answer them.

Millions of people might be tempted to erase a severely painful memory, for instance — but what if, in the process, they lost other, personally important memories that were somehow related? Would a treatment that “cleared” the learned habits of addiction only tempt people to experiment more widely?

And perhaps even more important, when scientists find a drug to strengthen memory, will everyone feel compelled to use it?

The stakes, and the wide-open opportunities possible in brain science, will only accelerate the pace of discovery.

“In this field we are merely at the foothills of an enormous mountain range,” said Dr. Eric R. Kandel, a neuroscientist at Columbia, “and unlike in other areas of science, it is still possible for an individual or small group to make important contributions, without any great expenditure or some enormous lab.”

Dr. Sacktor is one of hundreds of researchers trying to answer a question that has dumbfounded thinkers since the beginning of modern inquiry: How on earth can a clump of tissue possibly capture and store everything — poems, emotional reactions, locations of favorite bars, distant childhood scenes? The idea that experience leaves some trace in the brain goes back at least to Plato’s Theaetetus metaphor of a stamp on wax, and in 1904 the German scholar Richard Semon gave that ghostly trace a name: the engram.

What could that engram actually be?

The answer, previous research suggests, is that brain cells activated by an experience keep one another on biological speed-dial, like a group of people joined in common witness of some striking event. Call on one and word quickly goes out to the larger network of cells, each apparently adding some detail, sight, sound, smell. The brain appears to retain a memory by growing thicker, or more efficient, communication lines between these cells.

The billion-dollar question is how?

In the decades since this process was described in the 1960s and 1970s, scientists have found scores of molecules that play some role in the process. But for years the field struggled to pinpoint the purpose each one serves. The problem was not that such substances were so hard to find — on the contrary.

In a 1999 paper in the journal Nature Neuroscience, two of the most prominent researchers in brain science, Dr. Jeff W. Lichtman and Joshua R. Sanes of Harvard, listed 117 molecules that were somehow involved when one cell creates a lasting speed-dial connection with a neighbor, a process known as “long-term potentiation.”

They did not see that these findings were necessarily clarifying the picture of how memories are formed. But an oddball substance right there on their own list, it turned out, had unusual properties.

A Helpful Nudge

“You know, my dad was the one who told me to look at this molecule — he was a scientist too, my dad, he’s dead now but he had these instincts — so anyway that’s how it all started,” Dr. Sacktor was saying. He was driving from his home in Yonkers to his laboratory in the East Flatbush neighborhood of Brooklyn, with three quiches and bag of bagels bouncing in the back seat. Lunch for the lab.

The father’s advice led the son, eventually, to a substance called PKMzeta. In a series of studies, Dr. Sacktor’s lab found that this molecule was present and activated in cells precisely when they were put on speed-dial by a neighboring neuron.

In fact, the PKMzeta molecules appeared to herd themselves, like Army Rangers occupying a small peninsula, into precisely the fingerlike connections among brain cells that were strengthened. And they stayed there, indefinitely, like biological sentries.

In short: PKMzeta, a wallflower in the great swimming party of chemicals that erupts when one cell stimulates another, looked as if it might be the one that kept the speed-dial function turned on.

“After that,” Dr. Sacktor said, “we began to focus solely on PKMzeta to see how critical it really was to behavior.”

Running a lab is something like fielding a weekend soccer team. Players come and go, from Europe, India, Asia, Grand Rapids. You move players around, depending on their skills. And you bring lunch, because doctoral students logging 12-hour days in a yellowing shotgun lab in East Flatbush need to eat.

“People think that state schools like ours are low-key, laid back, and they’re right, we are,” said Robert K. S. Wong, chairman of the physiology and pharmacology department at SUNY Downstate, who brought Dr. Sacktor with him from Columbia. “You have less pressure to apply for grants, and you can take more time, I think, to work out your ideas.”

To find out what, if anything, PKMzeta meant for living, breathing animals, Dr. Sacktor walked a flight downstairs to the lab of André A. Fenton, also of SUNY Downstate, who studies spatial memory in mice and rats.

Dr. Fenton had already devised a clever way to teach animals strong memories for where things are located. He teaches them to move around a small chamber to avoid a mild electric shock to their feet. Once the animals learn, they do not forget. Placed back in the chamber a day later, even a month later, they quickly remember how to avoid the shock and do so.

But when injected — directly into their brain — with a drug called ZIP that interferes with PKMzeta, they are back to square one, almost immediately. “When we first saw this happen, I had grad students throwing their hands up in the air, yelling,” Dr. Fenton said. “Well, we needed a lot more than that” one study.

They now have it. Dr. Fenton’s lab repeated the experiment, in various ways; so has a consortium of memory researchers, each using a different method. Researchers led by Yadin Dudai at the Weizmann Institute of Science in Israel found that one dose of ZIP even made rats forget a strong disgust they had developed for a taste that had made them sick — three months earlier.

A Conscience Blocker?

“This possibility of memory editing has enormous possibilities and raises huge ethical issues,” said Dr. Steven E. Hyman, a neurobiologist at Harvard. “On the one hand, you can imagine a scenario in which a person enters a setting which elicits traumatic memories, but now has a drug that weakens those memories as they come up. Or, in the case of addiction, a drug that weakens the associations that stir craving.”

Researchers have already tried to blunt painful memories and addictive urges using existing drugs; blocking PKMzeta could potentially be far more effective.

Yet any such drug, Dr. Hyman and others argue, could be misused to erase or block memories of bad behavior, even of crimes. If traumatic memories are like malicious stalkers, then troubling memories — and a healthy dread of them — form the foundation of a moral conscience.

For those studying the biology of memory, the properties of PKMzeta promise something grander still: the prospect of retooling the engram factory itself. By 2050 more than 100 million people worldwide will have Alzheimer’s disease or other dementias, scientists estimate, and far more will struggle with age-related memory decline.

“This is really the biggest target, and we have some ideas of how you might try to do it, for instance to get cells to make more PKMzeta,” Dr. Sacktor said. “But these are only ideas at this stage.”

A substance that improved memory would immediately raise larger social concerns, as well. “We know that people already use smart drugs and performance enhancers of all kinds, so a substance that actually improved memory could lead to an arms race,” Dr. Hyman said.

Many questions in the science remain. For instance, can PKMzeta really link a network of neurons for a lifetime? If so, how? Most molecules live for no more than weeks at a time.

And how does it work with the many other substances that appear to be important in creating a memory?

“There is not going to be one, single memory molecule, the system is just not that simple,” said Thomas J. Carew, a neuroscientist at the University of California, Irvine, and president of the Society for Neuroscience. “There are going to be many molecules involved, in different kinds of memories, all along the process of learning, storage and retrieval.”

Yet as scientists begin to climb out of the dark foothills and into the dim light, they are now poised to alter the understanding of human nature in ways artists and writers have not.

courtesy: Newyorktimes

New Technologies Allow Scientists to Watch Cells in Motion

By CARL ZIMMER

It’s easy to imagine the cells in our bodies like bricks in a house, all cemented into place. But we are actually seething with cells that creep, crawl, and squirm. They start wandering soon after conception, and, throughout our lives, our bodies continue to hum with cellular traffic.

Some cells burrow into old bone so that new bone can be laid down in their wake. The tips of new blood vessels snake forward, dragging the cells behind along with them. White blood cells race along on flickering lobes to chase down bacteria before they can make us sick.

The fact that cells can move is old news. How they move is just now being understood. In the mid-1600s, Antonie van Leeuwenhoek built one of the first microscopes and observed single-cell organisms making what he called “pleasing and nimble” movements. But he had no idea what was going on inside those cells, and three centuries later, scientists were still baffled.

Thomas Pollard, a biochemist at Yale, started studying crawling cells in the 1960s, when, he said, “Exactly zero was known.” Today Dr. Pollard and his colleagues have identified many of the key proteins that work together to let cells navigate through our bodies. Scientists can even see some of these proteins at work in living cells and measure their forces.

“My dream was always to be a little gremlin, to get inside the cell and watch all this stuff,” Dr. Pollard said. “This is almost like being a little gremlin.

“We’ve gone from a black box to chemistry and physics.”

One of the chief reasons for these advances is the technology that scientists can now use to watch cells in motion. When developmental biologists first began to study how embryos grow, for example, they could only look at different stages under a microscope.

Today, they make high-resolution videos of embryos and track the movement of thousands of cells — videos that overturn some traditional ideas.

“There’s tremendously more migration than we thought,” said Scott Fraser, the director of the Biological Imaging Institute at Caltech.

To undertake the migrations that form an organism from an embryo, cells need to know where to go. An embryo is awash in signals that can guide them. Different kinds of cells respond to different signals. Cells that will give rise to skin, blood vessel walls and other linings of the body — epithelial cells — are attracted to a signaling protein called epidermal growth factor. Released by white blood cells in the embryo, this protein draws the cells crawling toward their source.

Eventually they stop traveling and form organs. But decades later they can still be roused to move again. As white blood cells wander through the skin, they may encounter a cut. They respond by releasing epidermal growth factor, summoning epithelial cells to help heal the wound. “They’re like traffic cops,” said John Condeelis, a biologist at Albert Einstein College of Medicine.

When a cell starts to move, it has to reorganize its interior. The inside of a cell is not a simple sack of jelly; it is stiffened by a network of wirelike molecules. At the core of the cell is a cluster of pipes called microtubules. Around the edges of the cell are thin filaments made of a molecule called actin.

In the late 1990s, Clare Waterman, a cell biologist, and her colleagues developed a way to capture this skeleton in motion. They would put glowing actin molecules in a cell, which would sometimes add them to its filaments. “It’s as if you were a bricklayer, and 99 percent of your bricks were gray and one percent were red,” said Dr. Waterman, who is now at the National Heart, Lung and Blood Institute at the National Institutes of Health.

Dr. Waterman and her colleagues at the University of North Carolina then took pictures of cells every few seconds to track the glowing molecules. They discovered that the filaments are in constant flux, even when the cell is not moving.

A stationary cell adds hundreds of new actin molecules each second to the outer end of each filament. At the same time, contracting proteins called myosins pull on the actin filament at the other end, as other proteins cut up the actin molecules. All of those reactions cause the actin molecules in a filament to move from the outer edge of the cell inward, as if they are on a treadmill.

A cell has to use a lot of energy to build and destroy the filaments. But its treadmilling is valuable because it allows a cell to respond quickly to signals by moving into motion. “It’s like a car,” Dr. Waterman said. “When you come to a stop light, you keep the engine running.”

To start crawling, a cell starts to build the leading edge of filaments faster than they tear down the back end. Other proteins help the actin filaments join into a branching network. The surface of the cell bulges out into a lobe. As the lobe stretches out from a cell, it grabs onto the underlying surface with molecular clamps. The clamps become joined to the growing actin filaments and drag the cell forward.

To further understand the process scientists at Yale have invented a new technique. “We basically play a tug of war,” said Eric Dufresne, a physicist. Dr. Dufresne and his colleagues implant beads on the tip of a neuron. The cell links the beads to filaments, and the beads move down the actin treadmills.

Dr. Dufresne and his colleagues then train lasers on the beads and use the energy of the beams to trap them. As the cells pull on the beads, the lasers pull back. The pull of the lasers lets the scientists measure the forces generated by many filaments at once.

A cell will tug at each bead, the scientists have found, for ten seconds or so before releasing it. A few minutes later, it will try to tug again. Dr. Dufresne suspects that the cells are continually testing their surroundings for good places to lay an anchor. As an advancing lobe drags a cell forward, the same signals trigger drastic changes in the rest of the cell. “It’s like squeezing a tube of toothpaste — everything get pushed to the front,” said Alan Hall, chair of the cell biology program at Memorial Sloan-Kettering Cancer Center.

The timing of these changes is carefully choreographed, as Dr. Waterman and her colleagues demonstrate in a paper to be published in Molecular Biology of the Cell. They found that skin cells called keratinocytes respond in several ways to epidermal growth factor. It causes keratinocytes to push out a lobe and make the lobe’s clamps stronger. At the same time, the pulse of growth factor also starts chemical reactions that loosen the same clamps after about 10 minutes. That’s amount of time it takes for the slow-moving keratinoctyes to roll over them. This intricate choreography is essential to our well-being. Immune cells have to chase down pathogens, for example. To form a brain, neurons sprout over a million miles of branches, and every time we learn new things, they sprout new ones.

But there are also times when cells move when they shouldn’t. When cancers become metastatic, some cells creep out of a tumor and make their way to other parts of the body.

To understand how cancer cells move, Dr. Condeelis and his colleagues have developed a microscope through which they can peer at tumors in living mice. The mice can be genetically engineered so that the cancer cells glow, allowing Dr. Condeelis and his colleagues to watch the cells creep out of their tumors.

In studies on mammary gland tumors, Dr. Condeelis and his colleagues have discovered that metastatic cancer cells are guided by the familiar signaling protein, epidermal growth factor, or E.G.F., produced by immune cells in nearby blood vessels.

Dr. Condeelis took advantage of this discovery to build a trap for cancer cells. He coated a plastic tube with E.G.F. and inserted it in a mouse mammary gland. The crawling cancer cells were drawn to the tube like flies to honey, and Dr. Condeelis and his colleagues removed the tube with the mobile cancer cells inside. They could then identify the genes that became active when cancer cells start crawling. The scientists found nothing peculiar about the cells. They were using the same genes to move as epithelial cells use in an embryo.

These results and others have led Dr. Condeelis to a surprising hypothesis about metatstatic breast cancer. “The cancer cells think they’re making another breast,” he said.

Dr. Condeelis argues that the peculiar environment inside a tumor fools some of the cells into thinking they’re inside an embryo. The cells release signals that attract white blood cells, which, in turn, release the growth factor that causes the cells to start moving.

But the cues that work in an embryo send cancer cells astray in an adult breast, and they end up in blood vessels, where they are carried away to other parts of the body.

Scientists have found that they can treat some diseases by interfering with the ability of cells to move when they shouldn’t. An eye disease called macular degeneration causes blood vessels to spread out too much over the retina. Drugs are now available that can block the cells in the blood vessels from getting the signals that trigger them to start crawling.

As scientists probe the inner workings of crawling cells, they’re looking for other ways to fight diseases. “The biggest thing is cancer therapy,” said Dr. Waterman.

It’s easy enough to imagine treating cancer by stopping cancer cells in their tracks, but many experts say it will be challenging to zero in on them without interfering with the crawling of normal cells. And without cells that can move, we cannot survive.

“We’re dealing with fundamental, universal stuff,” Dr. Pollard said.

Courtesy: Neyyork times

Jellyfish Fight Terrorists

Biochemists And Engineers Create Fast-acting Pathogen Sensor

Engineers invented a device to bring air samples into contact with genetically engineered biosensors in the effort to detect dangerous biological agents. The technology uses multiple collections of altered cell antibodies, each collection designed to respond to a specific pathogen by releasing photons of a unique wavelength upon finding it. Detectors measure the photons' wavelengths and interpret the pathogens they represent.

Anthrax, plague and small pox are some of the possible pathogens terrorists could use against us; but now, researchers say jellyfish are helping prevent these kinds of attacks.

From public transportation to federal and government buildings, experts are naming likely targets of bioterrorism.

Now, this innovative biosensor developed by scientists and engineers at Massachusetts Institute of Technology's (MIT) Lincoln Laboratory can identify harmful bacteria or viruses in the air in less than two minutes.

"It's at least ten times faster than any other automated sensor that's available," says James Harper, a biochemist and engineer at MIT.

In the lab, Todd Rider first developed the CANARY Sensor using jellyfish DNA and a high-voltage electrical charge. "I was in the lab with the electric creator," says Rider, a biologist at MIT. "I had mouse cells and the jellyfish DNA, and I frizzed my hair, said please give me life and pressed the buttons -- and the jellyfish DNA went inside the cells, and we had glowing mouse cells."

The glowing cells reveal the presence of a targeted pathogen. Still, scientists had no way to test air samples for pathogens until Harper created the PANTHER.

Scientists say operation is as simple as loading your DVD player. Disks containing sixteen chambers are loaded into the PANTHER. The machine pulls air through the disk to collect and test any pathogen that might be in the air. "That disk contains the cells that are the key to the canary technology," Harper says. "It releases those cells into the collected particles and looks for the resulting light, and gives you a sense of what's detected."

If a dangerous pathogen is detected, the sensor goes off -- alerting anyone who could be in harm's way.

Scientists and engineers say the CANARY technology can eventually be used for medical diagnostics to test patient samples. It may even be used in food processing plants to identify contaminants like E. coli or salmonella.

The technology is now licensed commercially.

WHAT IS PANTHER? The PANTHER device uses immune cells altered to act as detectors of dangerous biological agents. The device takes in air, runs it past the cells, which are gathered into groups, each designed to react to specific agent. The cells, which are engineered to respond to a specific pathogen, release photons of light when they detect their target. Other detectors recognize the release of light to indicate the pathogen that was detected. Based on the wavelengths of light that were released, the device outputs a list of dangerous pathogens that were found, about three minutes after beginning the test.

This report has also been produced thanks to a generous grant from the Camille and Henry Dreyfus Foundation, Inc.

Gamers Saving Lives

Computer scientists designed a computer game based on the principles of biochemistry. It allows amateurs to compete against and collaborate with specialists to design protein structures. Introductory levels teach the general governing concepts that users must understand before moving on to design complicated, potentially useful molecules.

What if instead of waging war or dropping blocks, gamers set their sights on something like a new HIV vaccine? Sounds strange, but biochemistry might be the new must-play video game.

It looks and sounds like a computer game, but Foldit is much more than just a computer game -- it's crucial biochemistry research.

Biochemist David Baker wants to discover the unique folding of proteins to better understand how they make our bodies work. A friend suggested turning this scientific puzzle into a game. That's where computer scientist Zoran Popovic and his team come in.

"You no longer need to get a degree in biochemistry to actually start doing this stuff," says Zoran Popovic, Ph.D., an associate professor in the department of Computer Science and Engineering at the University of Washington in Seattle.

The game's introductory levels "trick" you into learning all the concepts you need to know. Then all you do is play -- alone or in teams.

"I know that some of our users have kind of described it as Tetris on steroids or something," Dr. Popovic says. The goal is to get the highest score by folding the proteins based on the same criteria they use in the lab. Each protein is a puzzle -- the more people play, the better chance a correct "fold" will be discovered for each protein. Eventually the puzzles could be used to help make vaccines and even cure genetic diseases.

"You can get into work and say I stayed up all night -- [but] I wasn't playing Halo," says David Baker, Ph.D., a biochemist at the University of Washington in Seattle. "I was designing an HIV vaccine."

ABOUT COMPUTER MODELING: Computer modeling is used to represent the structure and appearance of both static objects, such as building architecture, and dynamic situations, such as a football game. With Foldit, game players have the opportunity to use a computer model to test the benefits of changing the structure of a protein. Foldit and other computer models can provide cutaway views that let users examine aspects of an object that are invisible even to the most powerful microscopes, as well as visualization tools that can provide many different perspectives. Computer models enable users to run companies and civilizations, fight battles, and play football games.

COMPLICATED MOLECULES: Polymers are large molecules made up of long repeating chemical units joined together in a chain, like beads on a string. Biological polymers are among the largest and most diverse molecules in the natural world, often containing billions of atoms. Human DNA is a polymer that can be thought of as billions of beads on a string. Proteins are polymers made up of 20 different amino acids, and the solid plastics used in a broad range of consumer products are polymers made of various types of "monomers" or smaller molecules. When monomers link together to form a polymer, this process is called polymerization, but they don't always link together in straight chains of regularly repeating monomers. Secondary molecules called catalysts can coax monomers to link together in certain configurations, and also speed up reaction times. This is how most synthetic polymers are created.

The American Association of Pharmaceutical Scientists contributed to this report. This report has also been produced thanks to a generous grant from the Camille and Henry Dreyfus Foundation, Inc.

Courtesy: Science daily news

Faster, More Cost-effective DNA Test For Crime Scenes, Disease Diagnosis

Scientists in Japan are reporting development of a faster, less expensive version of the fabled polymerase chain reaction (PCR) a DNA test widely used in criminal investigations, disease diagnosis, biological research and other applications. The new method could lead to expanded use of PCR in medicine, the criminal justice system and elsewhere, the researchers say.

In the new study, Naohiro Noda and colleagues note that PCR works by "amplifying" previously undetectable traces of DNA almost like photocopiers produce multiple copies of documents. With PCR, crime scene investigators can change traces of DNA into amounts that can be identified and linked to a suspect.

Biologists can produce multiple copies of individual genes to study gene function, evolution, and other topics. Doctors can amplify the DNA from microbes in a patient's blood to diagnose an infection. Current PCR methods, however, are too expensive and cumbersome for wide use.

The scientists describe development and testing of a new PCR method, called the universal QProbe system, that overcomes these problems. Existing PCR processes require several "fluorescent probes" to seek out DNA. QProbe substitutes a single "fluorescent probe" that can detect virtually any target, saving time and cutting costs. The new method also is more specific, accurately detecting DNA even in the presence of unfavorable PCR products in the samples that may interfere with quantification results.

Reference :

Hidenori Tani, Ryo Miyata, Kouhei Ichikawa, Soji Morishita, Shinya Kurata, Kazunori Nakamura, Satoshi Tsuneda, Yuji Sekiguchi, Naohiro Noda. Universal Quenching Probe System: Flexible, Specific, and Cost-Effective Real-Time Polymerase Chain Reaction Method. Analytical Chemistry, (in press) [link]

Scientists call up stem cell troops to repair the body using new drug combinations

Scientists have tricked bone marrow into releasing extra adult stem cells into the bloodstream, a technique that they hope could one day be used to repair heart damage or mend a broken bone, in a new study published today in the journal Cell Stem Cell.

When a person has a disease or an injury, the bone marrow mobilises different types of stem cells to help repair and regenerate tissue. The new research, by researchers from Imperial College London, shows that it may be possible to boost the body’s ability to repair itself and speed up repair, by using different new drug combinations to put the bone marrow into a state of ‘red alert’ and send specific kinds of stem cells into action.

In the new study, researchers tricked the bone marrow of healthy mice into releasing two types of adult stem cells – mesenchymal stem cells, which can turn into bone and cartilage and that can also suppress the immune system, and endothelial progenitor cells, which can make blood vessels and therefore have the potential to repair damage in the heart.

This study, funded by the British Heart Foundation and the Wellcome Trust, is the first to selectively mobilise mesenchymal stem cells and endothelial progenitor cells from the bone marrow. Previous studies have only been able to mobilise the haematopoietic type of stem cell, which creates new blood cells. This technique is already used in bone marrow transplants in order to boost the numbers of haematopoietic stem cells in a donor’s bloodstream.

The researchers were able to choose which groups of stem cells the bone marrow released, by using two different therapies. Ultimately, the researchers hope that their new technique could be used to repair and regenerate tissue, for example when a person has heart disease or a sports injury, by mobilising the necessary stem cells.

The researchers also hope that they could tackle autoimmune diseases such as rheumatoid arthritis, where the body is attacked by its own immune system, by kicking the mesenchymal stem cells into action. These stem cells are able to suppress the immune system.

Dr Sara Rankin, the corresponding author of the study from the National Heart & Lung Institute at Imperial College London, said: “The body repairs itself all the time. We know that the skin heals over when we cut ourselves and, similarly, inside the body there are stem cells patrolling around and carrying out repair where it’s needed. However, when the damage is severe, there are limits to what the body can do of its own accord.

“We hope that by releasing extra stem cells, as we were able to do in mice in our new study, we could potentially call up extra numbers of whichever stem cells the body needs, in order to boost its ability to mend itself and accelerate the repair process. Further down the line, our work could lead to new treatments to fight various diseases and injuries which work by mobilising a person’s own stem cells from within,” added Dr Rankin.

The scientists reached their conclusions after treating healthy mice with one of two different ‘growth factors’ – proteins that occur naturally in the bone marrow – called VEGF and G-CSF. Following this treatment, the mice were given a new drug called Mozobil.

The researchers found that the bone marrow released around 100 times as many endothelial and mesenchymal stem cells into the bloodstream when the mice were treated with VEGF and Mozobil, compared with mice that received no treatment. Treating the mice with G-CSF and Mozobil mobilised the haematopoietic stem cells – this treatment is already used in bone marrow transplantation.

The researchers now want to investigate whether releasing repair stem cells into the blood really does accelerate the rate and degree of tissue regeneration in mice that have had a heart attack. Depending on the outcome of this work, they hope to conduct clinical trials of the new drug combinations in humans within the next ten years.

The researchers are also keen to explore whether ageing or having a disease affects the bone marrow’s ability to produce different kinds of adult stem cells. They want to investigate if the new technique might help to reinvigorate the body’s repair mechanisms in older people, to help them fight disease and injury.

Source : http://www.imperial.ac.uk/press

Human Genomics in China

Ten years ago, the Chinese National Human Genome Center at Shanghai (South Center, hereafter) was established in the Zhangjiang HiTech Park of Pudong District in Shanghai. To commemorate this important event, which marks the beginning of the Genomics Era in China, we specially organize a series of mini-reviews for this special issue. We hope that this effort may draw the attention of the Chinese life science research workers to collectively recall the short but fruitful history of human genome project and coordinately explore the trend and goal of the future development of this academic discipline in China.

As early as in the late 1980s, the Chinese High Technology Research and Development Program, which is also known as the 863 Program, funded the scientists of Fudan University (in Shanghai) to construct DNA jumping library for human genetic disease related physical mapping. It was probably the very first human genome related research project supported by a national funding agency. After 1991, Fudan University, Ruijin Hospital and the Cancer Research Institute in Shanghai were all funded by the 863 Program in succession, to develop genomics technology by means of molecular genetics, and to study genetic diseases including cancer by means of medical genetics. Meanwhile, Beijing scientists such as those in the Institute of Basic Medicine, Chinese Academy of Medical Sciences also independently developed the rare cutter restriction enzymes such as Not I and Sfi I to facilitate the analysis of large DNA fragments of human genome, aiming at physical map construction. These early efforts and progress became truly “the spark of a fire” and the human genome research was thus initiated.

In the early 1990s, focusing on the total sequencing and annotation of the complete human genome as its core mission, the Human Genome Project (HGP) was initiated under the leadership of the U.S.A. However, the initial response in China was, instead, to participate in the International Rice Genome Project led by Japan. The reasons behind were obvious. First of all, for China, the largest developing country of the world, food security is of the primary concern and rice is the major staple food for Chinese people. Second, rice, a diploid crop, with its relatively small genome size (about 400 Mb), is a nice model of the monocotyledon plants. Third, over the years, the Chinese scientists had accumulated a great deal of experiences in the basic and applied research of rice, and achieved significant progress in rice breeding and physiology studies, particularly, for the hybrid rice, a model of “Green Revolution”. Inspired by these ideas, both the central and the Shanghai municipal governments supported the DNA sequencing expert HONG Guo-Fan, who just returned back to China from Sanger’s laboratory, to initiate the rice genome project in 1992 and the Chinese efforts in rice genome sequencing and research were thus, set out on its long journey.

Meanwhile, the far-sighted Chinese medical geneticists were still promoting the initiation of a human genome project in China. Academician WU Min, at that time, the director of the Department of Life Sciences, National Natural Science Foundation of China (NSFC), strongly recommended the NSFC committee to initiate some major projects for human genome research. His efforts were supported by the academician LIANG Dong-Cai, Deputy Director of the NSFC Committee and of the Department of Life Sciences, and thus, the first major human genome project in China was funded to study the genetic variations among the 56 Chinese nationalities. Meanwhile, the Chinese scientists working in the field of medical genetics gradually accepted the concept of genomics, and by applying the genomics technology, they carried out a series of research and made significant breakthroughs in the study and identification of disease associated genes, particularly the cloning and identification of genes related to leukemia, solid tumors (including liver cancer, colorectal cancer and nasopharyngeal cancer) and genetic diseases (such as deaf). Furthermore, substantial progresses were made in the development of technologies for human genome genotyping and genetic polymorphism detection, as well as for expressed sequence tag (EST) and full-length cDNA cloning and sequencing. All these achievements greatly strengthened the Chinese scientists’ confidence and encouraged them to further explore the human genome. On the other hand, they made people perceive and appreciate the Chinese human genetic resources, for their abundance in population (more than 1 billion) with 56 nationalities and numerous relatively isolated ethnic groups. If we actively collect and utilize the resources with intelligence in research, along with the HGP, we will be able to and obligatory to make great contributions to the course of human health, especially to the oriental people for the medical purpose.

With this scientific and historical background, in July 1997, the academician TAN Jia-Zhen petitioned the central government, appealing for the protection of the Chinese genetic resources, and proposed to establish the national human genome center to speed up the human genome research in China. This petition attracted great attention from the Party Central Committee and the State Council. JIANG Ze-Min, the General Secretary of the Party and the President of the People’s Republic of China, wrote: “One, who did not think far enough ahead, inevitably may have trouble right-a-way. We have to cherish our genetic resources.” Thus, the Shanghai Human Genome Research Center, co-sponsored by the Ministry of Science and Technology, Shanghai Municipal Government, Pudong District, Zhangjiang High-Tech Park, and six research institutions in Shanghai, was founded on March 4, 1998. On October 20, 1998, the center was officially inaugurated as the Chinese National Human Genome Center at Shanghai (abbreviated as the South Center), thus becoming the first national research center located in the Zhangjiang Hi-Tech Park of Pudong District. The academician CHEN Zhu has served as the director of the center ever since, while ZHAO Guo-Ping acted as the executive director of the center after 2002. At the same time, the National Human Genome Center at Beijing (the North Center) was established with the support of the Ministry of Science and Technology and Beijing Municipal Government, and the academician QIANG Bo-Qin served as the director. The “Huada” (Chinese Giant/Wash U) Genome Center, directed by YANG Huan-Ming, was also established by the Institute of Genetics, CAS. Together with the previously established National Gene Research Center, which was established by the joint efforts of both CAS and the Shanghai Municipality for rice genome research, a basic genomics sequencing and research framework formed in China, with Beijing and Shanghai each equipped with two genome centers. The connection between the human genome project and the rice genome project was greatly promoted, which eventually facilitated the success of the rice genome project.

The 9th National Five-Year Plan (1996-2000) witnessed the rise, the struggle and the success of the Chinese genomic research. In the early stage of the 9th Five-Year Plan, the scientific committee of the 863 Program thoroughly assessed the international trend of research related to human health and diseases and promptly de- termined to set up a “key project” for human genome research, and soon upgraded it as a “major project”. The committee set up a “two 1%” goal with respect to the genomic sequencing and the full-length cDNA identification, respectively, and coordinated the efforts of Shanghai and Beijing local government to set up the national human genome research centers for more efficient implementation. After acquiring the “one percent” share of human genome sequencing, the committee, together with CAS, promptly reinforced the support for the sequencing project. Coordinately, the National Key Basic Research Program, known as the 973 Program, started a disease genomics project in 1998 led by the academicians CHEN Zhu and QIANG Bo-Qin. The 973 Program continued to fund the project in 2004 under the title of “Systems Biology for the Multi-gene Complex Diseases” coordinated by CHEN Zhu.

The Chinese human genome project fully exemplified the “Chinese characteristics”. With respect to the project design, besides the above-mentioned “two one percent”, it reinforced the research upon disease genomics and focused on the establishment of the disease sample/information collecting network along with the continuous efforts in cloning and identification of disease related genes by employing human genetic resources from China and abroad. The human health oriented functional genomics research, including bioinformatics, transcriptomics, proteomics, structural genomics and other technology platforms, such as model animals, biochip constructions, etc., were all developed along with the human genomic sequencing project in the late 1990s. Making full use of the technology and resource advantages of the human genome research helped to extend the genomic sequencing and related research to plants other than rice, microorganisms (pathologens for medicine and agriculture or important industry bacteria), insects (silkworm) and parasites (Schistosoma japonicum). In 2006, the original and assembled genomic sequence data of S. japonicum was registered in and released from a public bioinformatics database (http://biodb.sgst.cn) . operated by the Shanghai Bioinformation Technology Development Center, for sharing with the international Schistosoma mansoni consortium. This action indicated that genomic information analysis technology had set out an important step forward in merging with the international GeneBank. In summary, although China started late in genomic sequencing, it has caught up with the international wave in functional genomics, and the achievements of which effectively enhanced the life science research and biotechnology development in China.

With respect to funding policy and the establishment of platform centers, China adopted the international model initially — organizing grand scientific program/projects and establishing genome centers for implementation. On the other hand, based on the characteristics of funding and administration systems in China, various kinds of operation models for those genome centers were explored in order to encourage all sections of the governmental institutions to offer as much as possible funds through various channels. By adopting these multiple funding patterns under the guidance of the national projects, the Chinese scientists mobilized as much enthusiasm from the society as possible and efficiently integrated the national and local, the governmental and social resources and secured the development of the projects and centers. Take the South Center as an example. During the ten years period since its establishment, in the process of completing a series of international and national key genome projects, the original mixed research team of the center was tempered, and the abilities of the team members were improved. Meanwhile, influenced by the center, an array of “omics” and systems biomedicine research centers were gradually set up in the Zhangjiang HiTech Park of Shanghai. Collaborating with these research centers, the South Center has been accomplishing its transformation from a platform technology center focusing on sequencing and genotyping services to a research center engaged in the cutting-edge innovation on molecular targets identification and characterization for human health and diseases and the translational research on genomics, molecular genetics and systems biomedicine. Meanwhile, through the constant improvement of its comprehensive competitiveness in science and technology innovation, the service function of this systems biology research platform is becoming more substantial, and the center continues to promote the formation and transformation of intellectual property based on the biomedicine research achievements.

As a matter of fact, within the past ten years, the progress of genomics in China was a sort of frogleap development in terms of scale, quality, interdisciplinarity, organization and international collaboration. The genomics research of human and rice, the two national major scientific projects, together with a series of genomic sequencing and functional genomics analyses, constitutes an unprecedented development in life science research and biotechnology development in China. For decades, particularly from the early 1950s to the 1970s, genetics and molecular genetics were sort of lagging in China, largely due to the influences of Lysenkonism in the 1950-1960s and then the hit by “culture revolution” in the 1960-1970s. Fortunately, in this difficult period, with the cooperation of Chinese biologists and chemists, protein and nucleic acid chemistry gained a rapid development. The chemical synthesis and 3D structure determination of bovine insulin and the chemical synthesis of yeast alanine-tRNA were land marker achievements recorded in the scientific history.

In contrast to the situation in China, from the 1960s to the 1980s, life science worldwide was led by genetics and molecular biology, i.e., studying DNA/RNA and the flow of genetic information (central dogma), whereas in China these disciplines were severely hampered, with few scientists such as Prof. TAN Jia-Zhen to be the only leading scientist to defend Morgan’s theory for a long time. That should be one of the reasons why China’s life science was largely behind the world development trend for decades. However, in the early 1990s, with the incoming “scientific spring”, Chinese life scientists grasped the historical opportunity of HGP to catch up with the world cutting-edge life science and realized a frogleap forward.

For the first time, the concept of “big science” was introduced into the Chinese life science community thanks to HGP. The “big sciences” are grand scientific research programs guided with a comprehensive and long-term objective to tackle the major scientific problems related to the development of human and human society. They aimed to gather important scientific data and to make significant scientific discoveries with the aid of multi-disciplinary studies and integrated technologies. A strong link between big and small sciences was set up, in that in the genomic era, no body doing small science related to molecular biology, biochemistry and cell biology won’t benefit from the dataset generated by human (and other) genomic studies. For instance, just in Shanghai, biologists engaging in molecular biology studies of mammalian reproductive system, signal transduction, immunology, microbiology, central nerve system, genetic evolution, leukemia pathogenesis and so on, were all somehow involved in genomics work to certain extent. The rise of other molecular “omics” further strengthened the linkage of “big science” and “small science”. For such a tremendous impact of this linkage upon life science research and the development of biotechnology, it is truly a revolution.

Human genome study in China initiated a new phase of interdisciplinarity in the history of life science in China. The rise of genomics relied on its integration with other academic disciplines, particularly in the following three areas. First, the integration with technology science has caused several rounds of revolution in DNA sequencing technology in the past 40 years, which directly led the first sequencing trial of 4 bases of the ? phage cos to the current program of sequencing the genomes of a thousand individuals. Second, the integration with computational science and computer technology brought about bioinformatics, which supported the system of data collection, administration, annotation, distribution, and services for genome researches; and the technology platform for data analysis was also thus established. Third, the integration with mathematics and statistics led to the rise of computational biology, which makes full use of the genomic data and the data generated by other “omics” and then, analyzes them with various kinds of biological data. It provides experimental scientists with hypotheses/models for systems biology research. Actually, mainly promoted by bioinformatics and computational biology, laws of a complex life system can now be deciphered and understood.

Human genomic research, with the magnitude of “big science “and “big project” and unprecedented dynamics of development, facilitated, in an extraordinary way, the domestic and international collaboration. HGP in China set a good example for “liberation of mind” in the life science fields. It makes the Chinese biologists to understand what the meaning of “leading the scientific frontier” is and what the “national strategic demand” is. It also inspired the Chinese biologists to challenge the important scientific problems and to participate in the international collaboration and competition. What’s more, it teaches the Chinese biologists how to organize scientific teams for major scientific research projects and how to efficiently coordinate the nation-wide research efforts. In the early 1990s, in the mind of the leaders of Chinese human genome research, a consensus had been reached, that is, “In the next century, China will be one of the leading countries in genomics and life science. If we do not start the genomics program today, we are going to lose the right of voice in 10 years. Though we start from small, we shall harvest huge.” To be honest, with ten years of persistent struggle and hard working, we keep our words and have mostly realized these objectives.

To recall the history is for a better development in the future. After the completion of the genomic sequencing and the HapMap project, the international HGP has entered an assault-fortified position aiming at studying the genetic mechanisms of human diseases and other phenotypes. The initiation of HGP is due to the lesson learnt from the failure of the cancer project in the Kennedy era of the 1960s, while the success of HGP also depends on its influence upon tackling cancer and other complex human diseases. Meanwhile, facilitated by the strategic plan of big sciences, the innovation of science and technology and their industrialization, as well as the fast progress in interdisciplinary studies such as bioinformatics, have prepared the ground for a new “great frogleap”. Some of the minireviews published in this issue analyze the future trend of genomics research and its scientific impact based on the technical perspectives of genomic sequencing, genotyping and functional genomics. While the others present the significant change of research strategy and technology brought in by the HGP with respect to liver cancer (hepatocarcinoma), immunology, and medical, environmental and industrial microbiology. These reviews reflect the progress we have achieved, showing that, compared with the situation ten years ago, our research capability, technology experience, and academic intelligence have all been significantly improved. Meanwhile, we are confronted with more difficult challenges than ten years ago. If we can learn from the past experience, focus on a correct direction, move forward bravely but with caution, carefully organize and integrate the research teams, improve the management with both democracy and discipline, and work hard to explore the scientific truth, we shall be able to make faster and greater progress. On the other hand, if we arrogantly enjoy the past but ignore the new challenge, or underestimate our capabilities and feel afraid of innovation, it is possible that we may miss the good opportunities, as said in this old Chinese proverb, “Ninety miles is only half way of a hundred-mile journey”.

Confucius once said: “The passage of time is just like the flow of the River, which goes on day and night, for ever”. The past glories are the momentum for our new journey, while the lessons of the past may teach us to be smarter. China, a developing socialist country rising from a hundred years of weakness and poverty, needs genomics to make historic contributions to the rejuvenation of the nation.

Source : http://zh.scichina.com/english/

Swine Flu

The World Health Organization declared the first flu pandemic in 41 years on 11 June. As details of the global impact of the 2009 influenza A (H1N1) virus — and efforts to combat the threat — unfold over the coming months, Nature News provides breaking news and authoritative analysis of the science and the politics behind the headlines.

• News
• Dealing with Pandemics
• History: Bird flu and the 1918 flu
• Research
• Elsewhere in Nature
  

On Malaria Struggle, Baboons And Humans Have Similar Stories To Tell

Evolutionarily speaking, baboons may be our more distant cousins among primates. But when it comes to our experiences with malaria over the course of time, it seems the stories of our two species have followed very similar plots.

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See also:
Health & Medicine

• Malaria
• Human Biology
• Genes

Plants & Animals

• Monkeys
• Evolutionary Biology
• Pests and Parasites

Reference

• Vector (biology)
• Transgenic plants
• Computational genomics
• Human biology

In humans, subtle variation in one particular gene that controls whether a protein on the surface of red blood cells gets made or not literally spells the difference between susceptibility or resistance to one form of malaria. That's because the blood protein serves as the entry point for Plasmodium vivax, one of several malaria-causing parasites that infect humans.

Now, researchers at the Duke Institute for Genome Sciences & Policy report that variation in precisely the same regulatory gene also influences baboons' chances of getting sick, by ratcheting their susceptibility to another, closely related parasite up or down.

"It's a nice example of how – in the vastness of the genome – the same gene was modified in the same way in two different species to produce the same kind of resistance," says Greg Wray, director of the IGSP's Center for Evolutionary Genomics. "That's a pretty remarkable thing when you think of all the different ways malaria resistance might have evolved."

The findings, which appeared online in Nature on June 24, also mark a turning point in primate research: they are the first to connect any functionally important genetic variation in wild primates to complex, real-life consequences for the animals.

The yellow baboons in question live in Kenya's Amboseli National Park and have been the subject of ongoing observation for nearly 40 years, making them one of the best-studied wild mammal populations in the world from a behavioral and life history standpoint.

"It used to be that our work was limited to 'skin-out' biology," says Susan Alberts, an associate professor of biology and IGSP member who has been recording the habits of the baboons for the last 25 years. Today, thanks to a growing library of sequenced primate genomes including our own, scientists can begin to delve deeper.

Graduate student Jenny Tung spent three summers out on the East African savanna, watching the baboons, collecting their DNA-laden feces, and with the help of an expert team of Kenyan field assistants, very carefully drawing blood from darted animals. Successfully darting baboons is no small feat, Tung said. You have to be within meters of the animal you are targeting, and at the same time make sure that none of the baboons catch you in the act. If they did, it would send the troop running and screaming and, in technical terms, "really mess up the field data." In the evenings, Tung processed and stored her hard-won samples in a makeshift refrigerator before shipping them off to Duke.

Once back at the lab, Tung found something in those blood samples that came as a surprise despite all the years of study. More than half of the Amboseli baboons -- some 60 percent -- were infected with the malaria-like parasite known as Hepatocystis.

"We had no idea so many of them were carrying this parasite," Alberts says. For years, researchers have tracked the baboons for any signs of injury or illness. But although the infection probably compromises the animals, they don't develop cyclical fever spikes or other immediately obvious symptoms like humans with malaria do.

In search of a genetic basis for differences in the baboons' vulnerability to infection, the researchers zeroed in on the DNA sequence surrounding the DARC gene, the same region that has been traced to malaria protection among people. Although the specifics differ from those in humans, they found that a single letter change to the genetic code -- a switch from an A to a G -- lends some baboons the ability to better fend off infection. In fact, they show, one G is good, but two are even better.

Further analysis of the baboons' blood and in cell culture confirmed that the variants influence infection rates through changes in the activity of the DARC gene. Comparison of the Amboseli baboon sequences to two other populations also showed that the DNA sequence has undergone a relatively rapid rate of evolutionary change, the mark of natural selection for malaria resistance.

The newfound parallels between baboons and humans bring the long history of conflict between parasite and host into high relief. "It's a struggle out there," Alberts says. "We often think of malaria as a contemporary problem, but it's a deep part of our history."

The study also shows the power of coupling genomics with dedicated fieldwork. "Part of what we want to do is push the envelope and show that this is doable," Wray says. With the proof of principle in hand, the next big challenge is to begin to unravel the genomic differences that may be responsible for fuzzier behavioral traits, such as social status or aggression, he added.

"It's getting easier and easier to generate genetic data," Tung says. "But it's never going to be easy to have long-term field data -- especially for primates. It takes years and years before you see the fruit of those labors. We're just at the point where it's going to really start paying off."

Collaborators on the study include Alexander Primus, Andrew Bouley and Tonya Severson, all of Duke. The work was funded by the National Science Foundation, the American Society of Primatologists, Duke University, the Duke chapter of Sigma Xi, and the Duke Institute for Genome Sciences & Policy.

Courtesy from Science Daily news:

Taiwan's hopes for a biotech revolution

The president of the country's top research institute on growing the knowledge economy.

David Cyranoski

Chi-Huey Wong.Academia Sinica

In October 2006, Chi-Huey Wong took over the reins of the Academia Sinica, Taiwan's top research institute. Convinced that Taiwan's former reliance on contract manufacturing is a dead end, Wong has been working closely with key government officials since then to help the country speedily establish its biotechnology industry. His experience in California — as Professor of Chemistry at the Scripps Research Institute, La Jolla, and, more importantly, as co-founder of Optimer Pharmaceuticals, San Diego — will be valuable in taking Taiwan into a new business sector. Nature News asks Wong how Taiwan will succeed when so many other countries are playing the same game?

Your predecessor, [Nobel laureate chemist] Yuan Tseh Lee, also chose to push the biotechnology industry. How will you be able to improve on what he did?

We had a thorough review of the status of biotech development in Taiwan, and concluded that we needed to do two things. First, we helped Congress pass a new Biotechnology and New Pharmaceutical Development Act in July of 2007. Now companies can get a 35% tax exemption for investment in research and development into new drugs and high-end medical devices. Also, the act enables inventors from academic institutions to serve as founders, board members or scientific advisors, and take equity in start-up companies. It is similar to the Bayh-Dole Act established in 1980 in the United States.

“I predict Taiwan will have at least 5% of the world market within 10 years.”

Chi-Huey Wong
Academia Sinica

Second, this April, the government passed a biotech development action plan, which paved the way for a US$2-billion venture capital fund, a new Food and Drug Administration (FDA), a super-incubator to provide core facilities as well as professional services and consultations, and expansion of the existing Development Center for Biotechnology to focus on preclinical development. These will help capitalize on Taiwan's strength in early-stage discoveries from Academia Sinica and universities. Two new biotech parks are being developed to facilitate this process.

What impact has this biotechnology-friendly legislation had so far?

We have seen momentum building in the sector. For example, 16 new companies were established to develop new drugs in the past two years, and currently there are about 20 new drugs in clinical development. More medical device companies were also formed, tech transfer activities increased and stock-exchange volume grew.

Some investors are sceptical about the prospects of biotech in Taiwan because of the small domestic market. What do you say to that?

We need to compete for the world market, including China. Taiwan's strength and experience in information and computer technologies could help with the biotech development, especially in medical devices, remote care, biobanking [storage for biological materials and data], and new medicines for diseases and genotypes commonly found in the Chinese community. We expect new products from our leading research in HBV [Hepatitis B], liver cancer and lung cancer; drug side-effects related to Steven-Johnson syndrome; and new vaccines for breast cancer and influenza.

Taiwan's advantages are early-stage discoveries and experience in late-stage clinical trials, respect for intellectual property and a solid regulatory system (similar to the US FDA system). What we need to do is to strengthen our translational research, so the early-stage discoveries can be translated into commercial opportunity.

How will you measure the success of your biotech initiatives? Do you have a target in terms of the number of biotech companies to be formed or the number of patents filed, for example?

Considering the number of biotech patents issued by the United States [Patent and Trademark Office], Taiwan is now ranked number 13 in the world. One-third of the patents are from Academia Sinica. But the bottom line is to see the outcome in terms of [biotechnology] market share. I predict Taiwan will have at least 5% of the world market within 10 years.

Taiwan is already struggling to cultivate and recruit top scientists. With fewer young bioscientists in Taiwan, how do you expect to keep up with China and other pressure on the scientific labour market?

This is a major challenge for Taiwan. As we move into the knowledge-based economy, we also need to make sure that we have enough talent to support and stimulate its growth. We have state-of-the art facilities and stable funding, but we also need to be more open and more flexible to recruit internationally, and provide reasonable salaries in order to be competitive. We have seen an increase in the hiring of foreign faculty members and recruitment of foreign graduate students and post-doctoral fellows at Academia Sinica and universities. I am sure a good portion of this foreign human capital will be integrated into our society to sustain our future development and prosperity.