Category Archives: Research

New Approach Builds Better Proteins Inside a Computer

With the aid of more than 150,000 home computer users throughout the world, Howard Hughes Medical Institute (HHMI) researchers have, for the first time, accurately predicted the three-dimensional structure of a small, naturally occurring globular protein using only its amino acid sequence. The accomplishment was achieved with a newly refined computational method for predicting protein structure, which the researchers say can also improve the detail and accuracy of protein structures generated with experimental techniques.

A detailed understanding of a protein’s structure can offer scientists a wealth of information – revealing intricacies about the protein’s biological function and suggesting new ideas for drug design. Researchers often rely on x-ray crystallography to determine a protein’s structure – bombarding the molecule with x-rays and analyzing the resulting diffraction pattern to piece together its structure. But not all proteins are amenable to this time-consuming technique, and those that are do not always yield the atomic-level data researchers would like to have.
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The complex algorithms the researchers developed to carry out these analyses demand a tremendous amount of computing power. More than 150,000 home computer users around the world were an integral part of the project, volunteering their computers to participate in the quest for protein structures through Rosetta@home, a distributed computing project that is based on the Berkeley Open Infrastructure for Network Computing (BOINC) platform.

You can join in via Rosetta@home. Related: Protein Knots – molecular sieve advances protein research – Protein Science Art – Nobel Laureate Discusses Protein Power

Live Long and Prosper

Live Long and Prosper: A Conversation with Cynthia Kenyon:

Cynthia Kenyon, PhD, director of the UCSF’s Larry L. Hillblom Center for the Biology of Aging, smiles a lot these days. And with good reason. She has aging cornered and she knows it. In less than 20 years, her once-crazy idea – that genes regulate aging – has not only gone mainstream, but spawned a huge field of research with giant conclaves and dozens of journal articles published every year.
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One of Kenyon’s lab rotation students – Ramon Tabtiang – in one of his very first experiments, picked a needle out of the haystack that is the C. elegans genome. In short, he found a mutant gene, dubbed daf-2, that made worms live twice as long. C. elegans was — and is — a favorite model for developmental biologists and geneticists because its simple structure and entire three-week life are easily scrutinized under the microscope.

Watching the mutant worms, says Kenyon, was like “witnessing a miracle.” Not only did these worms live longer, they retained good muscle tone, squirmed, sought food and stayed youthful. In comparison, normal, or wild, worms of the same two-week age were flabby, tattered and sedentary. They looked old. The message was clear. The rate of aging was not “fixed in stone,” after all. It could be slowed.

In the years since, Kenyon and her team have made more eye-popping discoveries, including the role of a companion gene, called daf-16, that controls on or off signals in still other genes. Learning more about the insulin pathway in which these genes operate helped her to understand a cascade of signals and responses as they reverberate through individual tissues.

Better yet, by using this information to tweak here and there in the worm genome, Kenyon and her laboratory colleagues have been able to extend a worm’s life up to six times the normal span, with no significant decline in vitality until late in life.

Popular Mechanics 2007 Breakthrough Award: the Windbelt

Shawn Frayne’s Windbelt Wins Popular Mechanics 2007 Breakthrough Award

Frayne’s device consists of a flat, taut membrane that flutters within its housing as air passes through it. At each end of the membrane are magnets that oscillate between metal coils as the band flutters, effectively creating an electric charge. According to the 28-year-old Frayne, prototypes of the Windbelt have generated 40 milliwatts in 10-mph slivers of wind, making his device 10 to 30 times as efficient as the best microturbines.
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Frayne, now based in Mountain View, Calif., gathered a variety of lessons while studying at MIT, especially under the tutelage of Amy Smith (a 2004 MacArthur fellow) in her “D-Lab” class. In this design lab, Frayne learned the politics of delivering technology to poor nations, as well as the technical aspects of mechanical engineering.

I blogged on Amy Smith another blog awhile back: Engineering a Better World (which includes a great web video). Read about 9 more Breakthrough awards.

New Hearing Mechanism

MIT finds new hearing mechanism

MIT researchers have discovered a hearing mechanism that fundamentally changes the current understanding of inner ear function. This new mechanism could help explain the ear’s remarkable ability to sense and discriminate sounds. Its discovery could eventually lead to improved systems for restoring hearing.
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t has been known for over half a century that inside the cochlea sound waves are translated into up-and-down waves that travel along a structure called the basilar membrane. But the team has now found that a different kind of wave, a traveling wave that moves from side to side, can also carry sound energy. This wave moves along the tectorial membrane, which is situated directly above the sensory hair cells that transmit sounds to the brain. This second wave mechanism is poised to play a crucial role in delivering sound signals to these hair cells.

Related: Solar Powered Hearing Aid

2007 Nobel Prize in Physics

Nobel Prize in Physics 2007

This year’s physics prize is awarded for the technology that is used to read data on hard disks. It is thanks to this technology that it has been possible to miniaturize hard disks so radically in recent years. Sensitive read-out heads are needed to be able to read data from the compact hard disks used in laptops and some music players, for instance.

In 1988 the Frenchman Albert Fert and the German Peter GrÃ¼nberg each independently discovered a totally new physical effect – Giant Magnetoresistance or GMR. Very weak magnetic changes give rise to major differences in electrical resistance in a GMR system. A system of this kind is the perfect tool for reading data from hard disks when information registered magnetically has to be converted to electric current. Soon researchers and engineers began work to enable use of the effect in read-out heads. In 1997 the first read-out head based on the GMR effect was launched and this soon became the standard technology. Even the most recent read-out techniques of today are further developments of GMR.

2007 Nobel Prize in Physiology or Medicine

Nobel Prize in Physiology or Medicine 2007 awarded to Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells”

This year’s Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.

Gene targeting is often used to inactivate single genes. Such gene “knockout” experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make “knockout mice” for all genes available within the near future.

Mario R. Capecchi, born 1937 in Italy, US citizen, PhD in Biophysics 1967, Harvard University, Cambridge, MA, USA. Howard Hughes Medical Institute Investigator and Distinguished Professor of Human Genetics and Biology at the University of Utah, Salt Lake City, UT, USA.

Sir Martin J. Evans, born 1941 in Great Britain, British citizen, PhD in Anatomy and Embryology 1969, University College, London, UK. Director of the School of Biosciences and Professor of Mammalian Genetics, Cardiff University, UK.

Oliver Smithies, born 1925 in Great Britain, US citizen, PhD in Biochemistry 1951, Oxford University, UK. Excellence Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.

The USA gains 2 Nobel Laureates born elsewhere – the incidence of this happening 30 years from now will be less I believe than it has been recently.

Finding Protease Inhibitors

Can’t Cut This by Kathleen M. Wong, ScienceMatters@Berkeley:

When a malaria parasite lands in your blood, one of the first things it does is whip out its scissors. As fast as it can, this protozoan snips the hemoglobin in red blood cells to get the nutrients it needs to survive. Of course, the microbe behind this deadly disease doesn’t actually deploy stainless-steel blades. Instead, it uses an array of biochemical scissors known as proteases.

Proteases are enzymes that snip proteins. They recognize certain strings of amino acids on a substrate protein, bind to this area, then break a nearby chemical bond. Proteases can destroy proteins by snipping them in half, as in malaria. They can also activate proteins by lopping off atoms covering a reactive site.

This versatility has made proteases critical to all manner of organisms, from viruses to plants to humans. Over the past 10 years, protease inhibitor drugs have become indispensable in the fight against AIDS, cardiovascular disease and diabetes. But finding protease inhibitors is no picnic. Humans manufacture tens of thousands of proteins; figuring out which of these a protease targets is extremely challenging and time consuming.
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Instead of mixing liquid chemicals and painstakingly purifying them again at each step, he attaches his precursor molecules to polystyrene beads resembling sand grains.

Blocking Bacteria From Passing Genes to Other Bacteria

Scientists are working on many fronts to keep deadly bacteria in check

Bacteria that cause cholera and bubonic plague turn from harmless to deadly with the flip of a genetic switch. Jam the switch and you might prevent infection, said Vladimir Svetlov, a microbiology research associate at Ohio State University and one of a group of scientists who defined the structure of a protein that appears to be the key. The discovery is one of many this year to identify structures and chemicals crucial to disease. All of this work could lead to new medicines.

At the same time, germs we once fought off with antibiotics are fighting back, forcing governments and health organizations worldwide to spend billions of dollars to find new remedies.
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Redinbo is part of a team that recently discovered that two osteoporosis drugs block a key site on E. coli bacteria, preventing it from passing antibiotic resistance genes to other E. coli.

By their nature, bacteria exchange pieces of their DNA with neighboring bacteria, leading to new forms that are virulent or resistant — or both. “This is not minor evolution,” said Irina Artsimovitch, associate professor of microbiology at Ohio State. “This is a huge genome exchange.”

Very cool stuff. Related: Antibiotic resistance: How do antibiotics kill bacteria? – Disrupting the Replication of Bacteria – Antibiotics Too Often Prescribed for Sinus Woes – Attacking Bacterial Walls

Google Lunar X Prize

The Google Lunar Xprize

seeks to create a global private race to the Moon that excites and involves people around the world and, accelerates space exploration for the benefit of all humanity. The use of space has dramatically enhanced the quality of life and may ultimately lead to solutions to some of the most pressing environmental problems that we face on earth – energy independence and climate change.
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we hope to usher in an era of commercial exploration and development, in which small companies, groups of individuals and universities can build, launch and explore the Moon and beyond.

Sergey Brin: “So now, we are here today embarking upon this great adventure of having a nongovernmental, commercial organization return to the Moon and explore. And I’m very excited that Google can play a part in it.”

Clues to Prion Infectivity

Structural Studies Reveal New Clues to Prion Infectivity

One of the unexplained questions facing prion researchers is how a single prion can apparently assume different conformations — with each conformation having different disease or phenotypic properties. Previous structural studies of prions had not yielded a clear understanding of the basis of strains because the prion protein is large and complex. Due to the size and complexity of prions, studies utilizing x-ray crystallography, a technique commonly used to determine the structure of proteins and other molecules, have been limited to short peptide fragments of the prion protein.

“There have been a number of fairly low-resolution pictures of prions that more or less proved that these different strains were in different conformations; but they really hadn’t established the nature of the different conformations,” Weissman said. “It was really a big black box. We basically didn’t have the conformation of any single prion, let alone the two prion protein strains in two different conformations.”
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““In our minds, our findings brought to a certain level of closure the understanding of the structural differences underlying strains,” said Weissman. “Now we understand the structural differences. We also have an idea how those differences lead to the differences in physical properties, and, in turn, how these differences in the physical properties lead to the phenotypic differences. We are starting to go all the way from the structural understanding of the different strains up to in vivo understanding of why they cause different behaviors inside the cell.”

Weissman noted that the findings offer a broader lesson to researchers studying prions and other proteins whose misfolding can cause disease. “Certainly, a bottom line from this study is that the rules of protein folding and the rules of protein misfolding are fundamentally different,” he said. “In many ways, we have to relearn basic principles of how proteins misfold. We have to forget many of the rules we learned from textbooks about protein folding because they are not necessarily applicable.”

Prions are very interesting. Related posts: Scientists Knock-out Prion Gene in Cows – Gene Study Finds Cannibal Pattern – Open Access Education Materials on Protein Folding