From Berkeley Lab: “New Imaging Technique Captures Ever-Changing World of Metabolites”

Berkeley Lab

June 12, 2013
Dan Krotz dakrotz@lbl.gov

“What would you do with a camera that can take a picture of something and tell you how new it is? If you’re Berkeley Lab scientists Katherine Louie, Ben Bowen, Jian-Hua Mao and Trent Northen, you use it to gain a better understanding of the ever-changing world of metabolites, the molecules that drive life-sustaining chemical transformations within cells.

The kinetic world of metabolites comes to life in this merged overlay of mass spectrometry images. It shows new versus pre-existing metabolites in a tumor section (yellow and red indicate newer metabolites). No image credit

They’re part of a team of researchers that developed a mass spectrometry imaging technique that not only maps the whereabouts of individual metabolites in a biological sample, but how new the metabolites are too.

That’s a big milestone, because metabolites are constantly in flux. They’re synthesized on-demand in order to sustain an organism’s energy requirements. When you eat lunch, metabolites momentarily fire up in various cell populations throughout your body to fuel your day. But they also have a dark side. Cancer cells tap metabolites to drive tumor development.

Unfortunately, the current ways to clinically analyze metabolites don’t capture their kinetics. Microscopy maps the cells and biomarkers in a tumor section. And traditional mass spectrometry reveals the abundance and spatial distribution of molecules such as metabolites.

But these images are static snapshots of a highly dynamic process. They’re blind to how recently the metabolites were synthesized, which is a key piece of information. The metabolic status of a cell population is a good indicator of what the cells were up to when the sample was taken.

To image the ebb and flow of metabolites, the scientists paired mass spectrometry with a clinically accepted way to label tissue that uses a hydrogen isotope called deuterium.

As recently reported in Nature Scientific Reports, they administered deuterium to mice with tumors. Newly synthesized lipids (a hallmark of metabolic activity) became labeled with deuterium, while pre-existing lipids remained unlabeled. The scientists then removed tumor sections and analyzed them with a type of mass spectrometry.

The resulting images look like freeze-frames of a slow-motion fireworks show. They reveal when and where metabolic turnover occurs in a tumor section, with the brighter colors depicting newly synthesized lipids.

The scientists also found that regions with new lipids had a higher tumor grade, which is a good predictor of how quickly a tumor is likely to grow.

‘Our approach, called kinetic mass spectrometry imaging, could provide clinicians with quantifiable information they can use,’ says Bowen.”

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From Berkeley Lab: “Berkeley Lab Researchers Increase NMR/MRI Sensitivity through Hyperpolarization of Nuclei in Diamond”

Berkeley Lab

June 05, 2013
Lynn Yarris (510) 486-5375 lcyarris@lbl.gov

“Today’s nuclear magnetic resonance (NMR) and Magnetic Resonance Imaging (MRI) technologies, like quantum information processing and nuclear spintronic technologies, are based on an intrinsic quantum property of electrons and atomic nuclei called ‘spin.’ Electrons and nuclei can act like tiny bar magnets with a spin that is assigned a directional state of either “up” or “down.” NMR/MRI signals depend upon a majority of nuclear spins being polarized to point in one direction. The greater the polarization, the stronger the signal. Researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) have reported on a technique for hyperpolarizing carbon-13 nuclear spins in diamond that enhances the sensitivity of NMR/MRI by many orders of magnitude above what is ordinarily possible with conventional NMR magnets at room temperature.

Hyperpolarizing carbon-13 nuclear spins in diamond holds implications for enhancing NMR/MRI sensitivity in applications related to molecular and biomolecular detection, diamond-based quantum information processing, and nuclear spintronics.

As part of a collaboration between the research groups of Alexander Pines and Dmitry Budker of Berkeley Lab’s Materials Sciences Division, Vikram Bajaj led the demonstration of the first magnetically-controlled nearly complete hyperpolarization of the spins of carbon-13 nuclei located near synthetic defects in diamond crystals. The work builds upon earlier research by several groups worldwide including those of Budker and Berkeley Lab’s Jeffrey Reimer. This spin hyperpolarization can be carried out with refrigerator-style magnets, resulting in predictable and robust control of carbon-13 hyperpolarization. The methodology suggests a route by which the sensitivity of generic NMR and MRI experiments can be enhanced in applications related to molecular and biomolecular detection, diamond-based quantum information processing, and nuclear spintronics.

Vikram Bajaj (left) and Alexander Pines led the demonstration of the first magnetically-controlled nearly complete hyperpolarization of the spins of carbon-13 nuclei located near nitrogen-vacancy centers in diamond crystals. (Photo by Roy Kaltschmidt)

‘The nearly complete polarization of the spin of carbon-13 nuclei is ideal for any process that requires a pure initial spin state,’ says Bajaj, who also holds an appointment with the University of California (UC) Berkeley as a project scientist for the California Institute for Quantitative Biosciences (QB3). ‘More importantly, our method should be applicable in any situation where hyperpolarized bulk atomic nuclei are required, including dynamic nuclear polarization-enhanced NMR and spintronic devices.’

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From Berkeley Lab: “Atom by Atom, Bond by Bond, a Chemical Reaction Caught in the Act”

Berkeley Lab

May 30, 2013
Paul Preuss 510-486-6249 paul_preuss@lbl.gov

“When Felix Fischer of the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) set out to develop nanostructures made of graphene using a new, controlled approach to chemical reactions, the first result was a surprise: spectacular images of individual carbon atoms and the bonds between them.

Almost as clearly as a textbook diagram, this image made by a noncontact atomic force microscope reveals the positions of individual atoms and bonds, in a molecule having 26 carbon atoms and 14 hydrogen atoms structured as three connected benzene rings.

‘We weren’t thinking about making beautiful images; the reactions themselves were the goal,’ says Fischer, a staff scientist in Berkeley Lab’s Materials Sciences Division (MSD) and a professor of chemistry at the University of California, Berkeley. ‘But to really see what was happening at the single-atom level we had to use a uniquely sensitive atomic force microscope in Michael Crommie’s laboratory.’ Crommie is an MSD scientist and a professor of physics at UC Berkeley.

What the microscope showed the researchers, says Fischer, ‘was amazing.’ The specific outcomes of the reaction were themselves unexpected, but the visual evidence was even more so. “Nobody has ever taken direct, single-bond-resolved images of individual molecules, right before and immediately after a complex organic reaction,” Fischer says.

The researchers report their results online in the May 30, 2013 edition of Science Express.

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From Berkeley Lab: “Models from Big Molecules Captured in a Flash”

Berkeley Lab

Berkeley Lab researchers and their colleagues create a new way to model biological molecules caught with a flash of x-rays

May 26, 2013
Paul Preuss 510-486-6249 paul_preuss@lbl.gov

“To learn how biological molecules like proteins function, scientists must first understand their structures. Almost as important is understanding how the structures change, as molecules in the native state do their jobs.

Existing methods for solving structure largely depend on crystallized molecules, and the shapes of more than 80,000 proteins in a static state have been solved this way. The majority of the two million proteins in the human body can’t be crystallized, however. For most of them, even their low-resolution structures are still unknown.

Fluctuation x-ray scattering is the basis of a new technique for rapidly modeling the shapes of large biological models, here demonstrated (gray envelopes) using existing diffraction data superposed on known high-resolution structures. Top left, lysine-arginine-ornithine (LAO) binding protein; top right, lysozome; bottom left, peroxiredoxin; and, bottom right, Satellite Tobacco Mosaic Virus (STMV).

Their chance to shine may have come at last, thanks to new techniques developed by Peter Zwart and his colleagues at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), working with collaborators from Arizona State University, the University of Wisconsin-Milwaukee, and DOE’s Pacific Northwest National Laboratory (PNNL). The new method promises a more informative look at large biological molecules in their native, more fluid state.

Diffraction before destruction

A key factor in new ways of looking at biomolecules is the data created by free-electron lasers (FELs) such as the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory, or the proposed Next Generation Light Source (NGLS), light sources whose powerful x‑ray pulses are measured in quadrillionths of a second. These pulses are faster than a molecule can rotate, and the experimental data reflects the state of the molecule frozen in time.

More to come. See the full article here.

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From Berkeley Lab: “Whirlpools on the Nanoscale Could Multiply Magnetic Memory”

Berkeley Lab

At the Advanced Light Source, Berkeley Lab scientists join an international team to control spin orientation in magnetic nanodisks

May 21, 2013
Paul Preuss 510-486-6249 paul_preuss@lbl.gov

‘We spent 15 percent of home energy on gadgets in 2009, and we’re buying more gadgets all the time,’ says Peter Fischer of the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab). Fischer lets you know right away that while it’s scientific curiosity that inspires his research at the Lab’s Advanced Light Source (ALS), he intends it to help solve pressing problems.

The electron spins in a magnetic vortex all point in parallel, either clockwise or counterclockwise. Spins in the crowded core of the vortex must point out of the plane, either up or down. The four orientations of circularity and polarity could form the cells of multibit magnetic storage and processing systems.

‘What we’re working on now could make these gadgets perform hundreds of times better and also be a hundred times more energy efficient,’ says Fischer, a staff scientist in the Materials Sciences Division. As a principal investigator at the Center for X-Ray Optics, he leads ALS beamline 6.1.2, where he specializes in studies of magnetism.

Fischer recently provided critical support to a team led by Vojtĕch Uhlíř of the Brno University of Technology in the Czech Republic and the Center for Magnetic Recording Research at the University of California, San Diego. Researchers from both institutions and from Berkeley Lab used the unique capabilities of beamline 6.1.2 to advance a new concept in magnetic memory.

‘Magnetic memory is at the heart of most electronic devices,’ says Fischer, ‘and from the scientist’s point of view, magnetism is about controlling electron spin.’

Magnetic memories store bits of information in discrete units whose electron spins all line up in parallel, pointing one way or the opposite to signify a one or a zero. What Fischer and his colleagues propose is multibit storage in which each unit has four states instead of two and can store twice the information.

See the full article here. This may effect a lot of what you do.

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From Berkeley Lab: “Brain Visualization Prototype Holds Promise for Precision Medicine”

Berkeley Lab

From the Computational Research Division

Berkeley Lab, UCSF and Oblong Industries Show Brain Browser at Summit

“The ability to combine all of a patient’s neurological test results into one detailed, interactive “brain map” could help doctors diagnose and tailor treatment for a range of neurological disorders, from autism to epilepsy. But before this can happen, researchers need a suite of automated tools and techniques to manage and make sense of these massive complex datasets.

Computational researchers from Berkeley Lab used existing computational tools to translate laboratory data collected at UCSF into 3D visualizations of brain structures and activity.

To get an idea of what these tools would look like, computational researchers from the Lawrence Berkeley National Laboratory (Berkeley Lab) are working with neuroscientists from the University of California, San Francisco (UCSF). So far, the Berkeley Lab team has used existing computational tools to translate UCSF laboratory data into 3D visualizations of brain structures and activity. Earlier this year, Los Angeles-based Oblong Industries joined the collaboration and implemented a state-of-the-art, gesture-based navigation interface that allows researchers to interactively explore 3D brain visualizations with hand poses movements.

This is terrific new science.

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From Berkeley Lab: “Comparing Proteins at a Glance”

Berkeley Lab

Berkeley Lab Researchers Unveil Technique for Easy Comparisons of Proteins in Solution

April 29, 2013
Lynn Yarris (510) 486-5375 lcyarris@lbl.gov

“A revolutionary X-ray analytical technique that enables researchers at a glance to identify structural similarities and differences between multiple proteins under a variety of conditions has been developed by researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab). As a demonstration, the researchers used this technique to gain valuable new insight into a protein that is a prime target for cancer chemotherapy.

Data in this revolutionary structural comparison map is presented as a color-coded checkerboard with similarity scores displayed as gradients moving from red, indicating high, to white, indicating low, and various shades of orange and yellow in between. No image credit

‘Proteins and other biological macromolecules are moving machines whose power is often derived from how their structural conformations change in response to their environment,’ says Greg Hura, a scientist with Berkeley Lab’s Physical Biosciences Division. ‘Knowing what makes a protein change has incredible value, much like knowing that stepping on a gas pedal makes the wheels of a car spin.’

Hura led the development of what is being called a structural comparison map for use with small angle X-ray scattering
(SAXS), an imaging technique for obtaining structural information about proteins and protein complexes in solution. Cynthia McMurray, a biologist with Berkeley Lab’s Life Sciences Division, provided the cancer-relevant protein used to test the new SAXS structural comparison map.

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From Berkeley Lab: “…Black Nanoparticles Could Play Key Role in Clean Energy Photocatalysis”

Berkeley Lab

“A unique atomic-scale engineering technique for turning low-efficiency photocatalytic “white” nanoparticles of titanium dioxide into high-efficiency “black” nanoparticles could be the key to clean energy technologies based on hydrogen.

Samuel Mao, a scientist who holds joint appointments with Berkeley Lab’s Environmental Energy Technologies Division and the University of California at Berkeley, leads the development of a technique for engineering disorder into the nanocrystalline structure of the semiconductor titanium dioxide. This turns the naturally white crystals black in color, a sign that the crystals are now able to absorb infrared as well as visible and ultraviolet light. The expanded absorption spectrum substantially improves the efficiency with which black titanium dioxide can use sunlight to split water molecules for the production of hydrogen.

Berkeley Lab’s Samuel Mao used disorder engineering to transform titanium nanocrystals into highly efficient solar hydrogen photocatalysts, a transformation marked by turning the crystals from white to black. (Photo by Roy Kaltschmidt)

‘We have demonstrated that black titanium dioxide nanoparticles are capable of generating hydrogen through solar-driven photocatalytic reactions with a record-high efficiency,’ Mao said in a talk at the American Chemical Society (ACS)’s national meeting in New Orleans.

‘The synthesis of black titanium dioxide nanoparticles was based on a hydrogenation process in which white titanium dioxide nanocrystals were subjected to high pressure hydrogen gas,’ said Mao. ‘The unique disordered structure creates a photocatalyst that is both durable and efficient, and gives titanium dioxide, one of the most-studied of all oxide materials, a renewed potential.’”

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From Berkeley Lab: “Sweet Success”

Berkeley Lab

Berkeley Lab Researchers Find Way to Catalyze More Sugars from Biomass

April 07, 2013
Lynn Yarris (510) 486-5375 lcyarris@lbl.gov

“Catalysis may initiate almost all modern industrial manufacturing processes, but catalytic activity on solid surfaces is poorly understood. This is especially true for the cellulase enzymes used to release fermentable sugars from cellulosic biomass for the production of advanced biofuels. Now, researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) through support from the Energy Biosciences Institute (EBI) have literally shed new light on cellulase catalysis.

PALM – for Photo-Activated Localization Microscopy – enables researchers to quantify how and where enzymes are binding to the surface of cellulose in heterogeneous surfaces, such as those in plant cell walls.

Using an ultrahigh-precision visible light microscopy technique called PALM – for Photo-Activated Localization Microscopy – the researchers have found a way to improve the collective catalytic activity of enzyme cocktails that can boost the yields of sugars for making fuels. Increasing the sugar yields from cellulosic biomass to help bring down biofuel production costs is essential for the widespread commercial adoption of these fuels.

From left, Jan Liphardt, Harvey Blanch and Doug Clark led the development of a way to improve the collective catalytic activity of enzyme cocktails that can boost the yields of sugars for making advanced biofuels. (Photo by Roy Kaltschmidt)

‘The enzymatic breakdown of cellulosic biomass into fermentable sugars has been the Achilles heel of biofuels, a key economic bottleneck,’ says chemical engineer Harvey Blanch, one of the leaders of this research. ‘Our research provides a new understanding of how multiple cellulase enzymes attack solid cellulose by working in concert, an action known as enzyme synergy, and explains why certain mixtures of cellulase enzymes work better together than each works individually.’”

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From Berkeley Lab: “Department of Energy Renews Joint BioEnergy Institute for Another Five Years”

Berkeley Lab

April 04, 2013
Lynn Yarris

“Reaffirming the Obama administration’s commitment to the development of sustainable alternatives to fossil fuel energy, the U.S. Department of Energy (DOE) has announced a five-year renewal of funding for the Joint BioEnergy Institute (JBEI), a Bay Area multi-institutional scientific partnership. Under the renewal, JBEI will be funded at the rate of $25 million annually through 2018.

JBEI is one of three DOE Bioenergy Research Centers (BRCs) established by DOE’s Office of Science in 2007 on the basis of a nationwide competition to accelerate fundamental research breakthroughs for the development of advanced, next-generation biofuels. Funded at $125 million for its first five-year period, JBEI was officially dedicated on December 2, 2008 at its state-of-the-art laboratory facility in Emeryville. Today the JBEI partnership, which is led by Lawrence Berkeley National Laboratory (Berkeley Lab), includes the Sandia National Laboratories, the University of California (UC) campuses of Berkeley and Davis, the Carnegie Institution for Science, the Pacific Northwest National Laboratory, and the Lawrence Livermore National Laboratory.

Said Energy Secretary Steven Chu, ‘Developing the next generation of American biofuels will enhance our national energy security, expand the domestic biofuels industry, and produce new clean energy jobs. It will help America’s farmers and create vast new opportunities for wealth creation in rural communities. By investing in innovative approaches and technologies at our Bioenergy Research Centers, we can continue to move the biofuels industry forward and grow our economy while reducing our reliance on foreign oil.’”

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