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Archive - Mar 13, 2011

Single Cell Sequencing Suggests Tumors Evolve in Staccato-Like Bursts

A new method of analyzing cancerous tumors developed by scientists at Cold Spring Harbor Laboratory (CSHL) suggests that tumors may not evolve gradually, but rather in punctuated or staccato-like bursts. It is a finding that has already shed new light on the process of tumor growth and metastasis, and may help in the development of new methods to clinically evaluate tumors. The new analytic method, devised by CSHL Professor Michael Wigler and colleagues, features a process called single cell sequencing (SNS), which enables accurate quantification of genomic copy number within a single cell nucleus. In cancer, portions of the genome are amplified or deleted, giving rise to extra or missing copies of key genes and interfering with mechanisms that normally control cell growth. In a study published online on March 13, 2011, in the journal Nature, "we demonstrated that we can obtain accurate and high-resolution copy number profiles by sequencing a single cell from a cancerous tumor," said Dr. Wigler, "and that by examining multiple cells from the same cancer, we can make inferences about how the cancer evolved and spread." The CSHL team also included Professor W. Richard McCombie, Assistant Professor Alex Krasnitz and Research Professor James Hicks. Nicholas Navin, the paper's first author, was a graduate student while pursuing the research at CSHL and is now Assistant Professor at the MD Anderson Cancer Center in Texas. It has been very difficult for scientists to translate their growing ability to classify tumors at the molecular level into methods and tests that can be used in the clinic to analyze tumors in actual patients.

Major Breakthrough in Materials Design for Hydrogen Storage

Since the 1970s, hydrogen has been touted as a promising alternative to fossil fuels due to its clean combustion —unlike hydrocarbon-based fuels, which spew greenhouse gases and harmful pollutants, hydrogen's only combustion by-product is water. Compared to gasoline, hydrogen is lightweight, can provide a higher energy density, and is readily available. But there's a reason we're not already living in a hydrogen economy: to replace gasoline as a fuel, hydrogen must be safely and densely stored, yet easily accessed. Limited by materials unable to leap these conflicting hurdles, hydrogen storage technology has lagged behind other clean energy candidates. In recent years, researchers have attempted to tackle both issues by locking hydrogen into solids, packing larger quantities into smaller volumes with low reactivity—a necessity in keeping this volatile gas stable. However, most of these solids can only absorb a small amount of hydrogen and require extreme heating or cooling to boost their overall energy efficiency. Now, scientists with the U.S. Department of Energy (DOE) Lawrence Berkeley National Laboratory (Berkeley Lab) have designed a new composite material for hydrogen storage consisting of nanoparticles of magnesium metal sprinkled through a matrix of polymethyl methacrylate, a polymer related to Plexiglas. This pliable nanocomposite rapidly absorbs and releases hydrogen at modest temperatures without oxidizing the metal after cycling—a major breakthrough in materials design for hydrogen storage, batteries, and fuel cells. "This work showcases our ability to design composite nanoscale materials that overcome fundamental thermodynamic and kinetic barriers to realize a materials combination that has been very elusive historically," said Dr.

Rhodopsin May Also Be Involved in Temperature Sensation

New research from the Mount Sinai School of Medicine has revealed that rhodopsin, a pigment of the retina that is responsible for the first events in the perception of light, may also be involved in temperature sensation. This detection had not been revealed in previous studies. The work emerged from a collaboration between the laboratory of Dr. Andrew Chess, Professor in the Departments of Neuroscience, Developmental and Regenerative Biology and Genetics and Genomic Sciences at Mount Sinai, and the laboratory of Dr. Craig Montell, Professor of Biological Chemistry at Johns Hopkins School of Medicine. Their paper is published in the March 11 issue of Science. The research focused on rhodopsin in Drosophila larvae. The temperature-detection function of rhodopsin allows the Drosophila larvae to move to their preferred temperature of 18 degrees Celsius (64.4 degrees Fahrenheit). This ability depends on a thermosensory signaling pathway that includes a heterotrimeric guanine nucleotide-binding protein, or G-protein. "It is very surprising that rhodopsin has a role in temperature sensation, as it was thought to be completely devoted to its well-known role as a light sensor," said Dr. Chess. "This function of rhodopsin allows temperature discrimination in the comfortable range." This new role for rhodopsin emerged from studies of the process that results in the activation of a temperature-sensor protein known as a TRPA1, which Dr. Montell's group has been studying. The researchers released about 75 larvae onto a plate with two temperature zones. Half of the plate was kept at 18 degrees Celsius and the other half ranged from 14 to 32 degrees Celsius. After ten minutes, the larvae lacking rhodopsin could not discriminate temperatures in comfortable range, just like the larvae lacking TRPA1.

International Project to ID Antibiotics for Tuberculosis

Scientists are collaborating on a new international research project to identify antibiotics that can kill tuberculosis and fight resistant strains. "We want to accelerate the discovery of new compounds that can be turned into effective drugs," said Professor Tony Maxwell from the John Innes Centre, a key player in "More Medicines for Tuberculosis," a new European-centered research project. Two billion people are currently infected with TB and three million die every year. TB causes more deaths than any other infectious disease. Rates are increasing, especially in sub-Saharan Africa, where people with HIV are particularly vulnerable. It is also associated with intravenous drug use and increased rates may be linked to immigration. "The bacterium is difficult to get at," said Professor Maxwell. "It is slow growing, spends a lot of time hidden in cells before it makes itself known, and has very tough cell walls of its own." Treatment is relatively long term, requiring a drug regimen over four to six months. Non-compliance is a problem, exacerbating the challenge caused by resistant strains. "Drug discovery research for tuberculosis is dependent on academic labs and no single lab can do it," said Professor Maxwell. Scientists from 25 labs across Europe will collaborate on the new project as will some groups in the US and India. The John Innes Centre scientists will focus on compounds that target DNA gyrase, a target that they have already established as effective and safe. They will receive compounds from European collaborators including AstraZeneca. They will screen those that knock out DNA gyrase. Their research will continue on those compounds that are effective both against the target (DNA gyrase) and the bacterium.

Leaf Beetle Alters Defense Mechanism for Birch-Feeding Versus Willow-Feeding

Larvae of the leaf beetle Chrysomela lapponica attack two different tree species: willow and birch. To fend off predator attacks, the beetle larvae produce toxic butyric acid esters or salicylaldehyde, whose precursors they ingest with their leafy food. Scientists of the Max Planck Institute for Chemical Ecology in Jena, Germany, and colleagues have now found that a fundamental change in the genome has emerged in beetles that have specialized on birch: The activity of the salicylaldehyde-producing enzyme salicyl alcohol oxidase (SAO) is missing in these populations, whereas it is present in willow feeders. For birch beetles, the loss of this enzyme and thereby the loss of salicylaldehyde is advantagous: the enzyme is not needed anymore because its substrate salicyl alcohol is only present in willow leaves, but not in birch. Birch beetles can therefore save resources instead of producing the enzyme at a cost. First and foremost, however, the loss of salicylaldehyde also means that birch-feeding populations do not betray themselves to their own enemies anymore, that can trace them because of the odorous substance. These new findings were reported online on March 7, 2011, in PNAS. Beetle larvae are part of a food chain. They are attacked by predatory insects and parasites, such as hover flies and bugs, as well as infested by bacteria and fungi. To protect themselves, some leaf beetle larvae have developed interesting defense mechanisms, which function externally and metabolically: In case of danger, they emit substances from their defensive glands in form of vesicles (a short video is available at http://www.ice.mpg.de/ext/735.html). These defensive secretions contain toxins that the larvae sequester from chemical precursors they have ingested with their plant food.