Undergrad Has Sweet Success With Invention of Artificial Golgi
An undergraduate student at Rensselaer Polytechnic Institute has learned very quickly that a spoonful of sugar really does help the medicine go down. In fact, with his invention, the sugar may actually be the medicine.
Among the most important and complex molecules in the human body, sugars control not just metabolism but also how cells communicate with one another. Graduating senior Jeffery Martin has put his basic knowledge of sugars to exceptional use by creating a lab-on-a-chip device that builds complex, highly specialized sugar molecules, mimicking one of the most important cellular structures in the human body — the Golgi Apparatus.
“Almost completely independently he has been able to come closer than researchers with decades more experience to creating an artificial Golgi,” said Robert Linhardt, the Ann and John H. Broadbent Jr. ‘59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer and Martin’s adviser. “He saw a problem in the drug discovery process and almost instantly devised a way to solve it.”
Cells build sugars in a cellular organelle known as the Golgi Apparatus. Under a microscope, the Golgi looks similar to a stack of pancakes. The strange-looking organelle finishes the process of protein synthesis by decorating the proteins with highly specialized arrangements of sugars. The final sugar-coated molecule is then sent out into the cell to aid in cell communication and to help determine the cell’s function in the body.
Martin’s artificial Golgi functions in a surprisingly similar way to the natural Golgi, but he gives the ancient organelle a very high-tech makeover. His chip looks similar to a miniature checker board where sugars, enzymes, and other basic cell materials are suspended in water and can be transported and mixed by applying electric currents to the destination squares on the checker board. Through this process sugars can be built in an automated fashion where they are exposed to a variety of enzymes found in the natural Golgi. The resulting sugars can then be tested on living cells either on the chip or in the lab to determine their effects. With the chip’s ability to process many combinations of sugars and enzymes, it could help researchers quickly uncover new sugar-based drugs, according to Martin.
Scientists have known for years that certain sugars can serve as extremely beneficial therapeutics for humans. One well-known example is heparin, which is among the most widely used drugs in the world. Heparin is formed naturally in the Golgi organelle in cells of the human body as well as in other animals like pigs. Heparin acts as an anticoagulant preventing blood clots, which makes it a good therapeutic for heart, stroke, and dialysis patients.
The main source of heparin is currently the intestines of foreign livestock and, as recent news reports highlight, the risk of contamination from such sources is high. So researchers are working around the clock to develop a safer, man-made alternative to the drug that will prevent outside contamination. A synthetic alternative would build the sugar from scratch, helping eliminate the possibility of contamination he explained.
“I am very grateful to have the privilege of working with Dr. Linhardt who has discovered the recipe to make fully synthetic heparin,” Martin said. “Because we know the recipe, I am going to use it as a model to test the device. If our artificial Golgi can build fully functional heparin, we can then use the artificial organelle to produce many different sugar variants by altering the combination of enzymes used to synthesize them. Another great thing about these devices is that they are of microscale size, so that if needed we could fill an entire room with them to increase throughput for drug discovery.”
There are millions of possible sugar combinations that can be formed and scientists currently only know the function of very few of them like heparin. “Since it is known that these types of sugars play a part in many important biological processes such as cell growth, cell differentiation, blood coagulation, and viral defense mechanisms, we feel that that this artificial Golgi will help our team to develop a next generation of sugar-based drugs, known as glycotheraputics,” Martin said. “We are going to start making new combinations and we simply don’t know what we are going to find. We could find a sugar whose signal blocks the spread of cancer cells or initiates the differentiation of stem cells. We just don’t know.”
Martin, a Barry M. Goldwater Scholar and native of the small town of Boylston, Mass., is graduating from Rensselaer on May 17, 2008 with a nearly perfect GPA. He plans to continue on at Rensselaer as a graduate student, working with Linhardt to test and further develop his artificial Golgi.
[Gabrielle DeMarco @ Rensselaer Polytechnic Institute]
Eddy Arnold Dies
Country music superstar, Eddy Arnold, has died. Arnold died at a care facility near Nashville, just a few days short of his 90th birthday. via WJBF-TV Augusta
Pioneer unveils two Blu-ray players
Pioneer's "budget" Blu-ray player will still set you back $600. Pioneer announced two new Blu-ray players Wednesday morning, the BDP-51FD and step-up Elite BDP-05FD. Pioneer has so far taken a decidedly ... via CNET News.com
High Fuel Prices Could Slash U.S. Emissions
High gasoline prices could lead to a dramatic saving in US greenhouse-gas emissions. That’s the conclusion of economists in the US, who suggest high fuel prices are turning consumers off SUVs and onto smaller, more fuel-efficient vehicles.
What’s more, car owners are predicted to cut back on driving in order to save money. Together, these changes in consumer behaviour could make an important dent in the US contribution to global warming, reducing annual carbon dioxide emissions by tens of millions of tonnes per year. The impact will be dramatic, says Chris Knittel, an economist at the University of California, Davis, who was involved in one of the studies.
The changes are being driven by record fuel prices in the US, where, at the end of April, the average price of gasoline stood at $3.65 per gallon, 20 percent more than in January and treble the price of a decade ago. Until recently, these increases did not seem to be having a consistent effect on the car market and fuel use. Though sales of SUVs in the US have been falling over the past few years, this decline has come on the back of years of rapid growth, and overall gasoline consumption has been increasing every year since 1991.
That could be about to change. Knittel and colleagues looked at data on 1.4 million car purchases over the past 10 years, comparing sales patterns with gas prices. They found that sales of the least fuel-efficient cars, such as SUVs and pick-up trucks, fell by 13 percent for every $1 per gallon increase in the price of gasoline. The biggest SUVs suffered the most, with sales dropping by over 25 percent for every dollar by which the gas price rose. And for every $1 hike in gas prices there was a corresponding 17 percent sales boost for the most efficient vehicles, such as compact cars and hybrids. Knittel estimates that over about a decade, such changes in buying habits could cut the amount of gasoline used by US drivers by around 7 percent for every $1 increase in its price.
Knittel’s findings, presented last month at the University of California Energy Institute in Berkeley, are in broad agreement with those of economist Kenneth Small of the University of California, Irvine. Small looked at data on US fuel consumption and prices over the past 40 years, and projected last year that the recent doubling in fuel prices would quickly lead to a 4 percent drop in the total mileage covered on the roads. In the longer term, as drivers continue to react to rising prices, he projects the size of the reduction will grow to around 20 percent (The Energy Journal, vol 28, p 25).
This would lead to a substantial reduction in carbon emissions. Small says that a $1 per gallon rise in gasoline prices, roughly that seen over the past two years, will result in motorists using 14 percent less fuel in the long term. That would avoid the release of some tens of millions of tonnes of CO2 per year, equivalent to roughly 2 percent of the country’s greenhouse-gas emissions for 2006. That is a hugely significant drop, close to the level of cuts that some nations are required to make under the Kyoto protocol.
Small’s prediction comes with major caveats, however. Gasoline prices are not expected to return to the lows of a decade ago, but could fall by 10 or 20 percent in coming years. And any US economic recovery will boost fuel consumption, partly through raising incomes, which would dilute the pressure on motorists to drive less. So while expensive fuel will rein in consumption, Small and other economists question whether this will be enough to cause an overall fall in emissions from cars.
It is also possible that politics will intervene before any of these effects has a chance to kick in. Presidential hopefuls John McCain and Hillary Clinton have reacted to consumer protests over soaring fuel prices by declaring that they would suspend federal gasoline taxes. “It’s a fantastically stupid idea,” says Roberton Williams, an economist at the University of Texas at Austin.
“But people don’t like high gas taxes, so it’s popular.”
[Claire Bowles @ New Scientist]
Shopping Coupons and Codes
This feed is fueled by Lockergnome Online Shopping and Coupon Codes
Platypus Genome Explains Animal’s Peculiar Features
An international consortium of scientists, led by Washington University School of Medicine in St. Louis, has decoded the genome of the platypus, showing that the animal’s peculiar mix of features is reflected in its DNA. An analysis of the genome, published today in the journal Nature, can help scientists piece together a more complete picture of the evolution of all mammals, including humans.
The platypus, classified as a mammal because it produces milk and is covered in a coat of fur, also possesses features of reptiles, birds and their common ancestors, along with some curious attributes of its own. One of only two mammals that lays eggs, the platypus also sports a duck-like bill that holds a sophisticated electrosensory system used to forage for food underwater. Males possess hind leg spurs that can deliver pain-inducing venom to its foes competing for a mate or territory during the breeding season.
“The fascinating mix of features in the platypus genome provides many clues to the function and evolution of all mammalian genomes,” says Richard K. Wilson, Ph.D., director of the The Genome Center at Washington University and the paper’s senior author. “By comparing the platypus genome to other mammalian genomes, we’ll be able to study genes that have been conserved throughout evolution.”
The platypus represents the earliest offshoot of the mammalian lineage some 166 million years ago from primitive ancestors that had features of both mammals and reptiles. “What is unique about the platypus is that it has retained a large overlap between two very different classifications, while later mammals lost the features of reptiles,” says Wes Warren, Ph.D., an assistant professor of genetics, who led the project.
Comparison of the platypus genome with the DNA of humans and other mammals, which diverged later, and the genomes of birds, whose ancestors branched off an estimated 315 million years ago, can help scientists fill gaps in their understanding of mammalian evolution. The comparison also will allow scientists to date the emergence of genes and traits specific to mammals.
The Nature paper analyzes the genome sequence of a female platypus named Glennie from New South Wales, Australia. The project was largely funded by the National Human Genome Research Institute, part of the National Institutes of Health, and includes scientists from the United States, Australia, England, Germany, Israel, Japan, New Zealand and Spain.
“At first glance, the platypus appears as if it was the result of an evolutionary accident,” says Francis S. Collins, M.D., Ph.D., director of NHGRI. “But as weird as this animal looks, its genome sequence is priceless for understanding how mammalian biological processes evolved.”
“While we’ve always been able to compare and consider all of these creatures on the basis of their physical characteristics, internal anatomy and behavior, it’s truly amazing to be able to compare their genetic blueprints and begin to get a close-up look at how evolution brings about change,” Wilson says.
As part of their analysis, the researchers compared the platypus genome with genomes of the human, mouse, dog, opossum and chicken. They found that the platypus shares 82 percent of its genes with these animals. The chicken genome was chosen because it represents a group of egg-laying animals, including extinct reptiles, which passed on much of their DNA to the platypus and other mammals over the course of evolution.
The researchers also found genes that support egg laying - a feature of reptiles - as well as lactation - a characteristic of all mammals. Interestingly, the platypus lack nipples, so its young nurse through the abdominal skin.
The researchers also attempted to determine which characteristics of the platypus were linked to reptiles at the DNA level. When they analyzed the genetic sequences responsible for venom production in the male platypus, they found it arose from duplications in a group of genes that evolved from ancestral reptile genomes. Amazingly, duplications in the same genes appear to have evolved independently in venomous reptiles.
The platypus swims with its eyes, ears and nostrils closed, relying on electrosensory receptors in its bill to detect faint electric fields emitted by underwater prey. Surprisingly, the researchers found the genome contains an expansion of genes that code for a particular type of odor receptor. “We were expecting very few of these odor receptor genes because the animals spend the majority of their life in the water,” Warren says.
Similar genes are found in animals that rely on a sense of smell, such as rodents and dogs, and the scientists suspect that their addition in the platypus allows the animals to detect odors while foraging underwater.
At roughly 2.2 billion base pairs, the platypus genome is about two-thirds the size of the human genome and contains about 18,500 genes, similar to other vertebrates. The animal has 52 chromosomes, including an unusual number of sex chromosomes: 10. The platypus X chromosome bears resemblance to the sex chromosome of a bird, known as Z.
Sequencing and assembling the platypus genome proved far more daunting than sequencing any other mammalian genome to date. About 50 percent of the genome is composed of repetitive elements of DNA, which makes it a challenge to assemble properly.
The platypus genome sequence, along with those for other organisms, such as the mouse, dog, cow, and many other animals can be accessed at GenBank (www.ncbi.nih.gov/Genbank) at NIH’s National Center for Biotechnology Information.
[Caroline Arbanas @ Washington University School of Medicine]
