Category Archives: Chemistry

Biologists Discover How Viruses Hijack Cell’s Machinery

Biologists at UC San Diego have documented for the first time how very large viruses reprogram the cellular machinery of bacteria during infection to more closely resemble an animal or human cell—a process that allows these alien invaders to trick cells into producing hundreds of new viruses, which eventually explode from and kill the cells they infect.

In a paper published in the journal Science, the researchers conducted a series of experiments that allowed them to view in detail what happens inside bacterial cells as the invading viruses replicate.

“Scientists have been studying viruses for a hundred years, but we’ve never seen anything like this before,” said Joe Pogliano, a professor of molecular biology who headed the research team. “Every experiment produced something new and exciting about this system.”

Cryo-electron tomography shows how the bacterial cell is reorganized to resemble a more complicated plant or animal cell with a red nucleus-like compartment and ribosomes, the smaller light blue structures. The reproducing viruses appear with dark blue heads and pink tails. Image by Vorrapon Chaikeeratisak, Kanika Khanna, Axel Brilot, Katrina Nguyen

Viruses that infect bacteria, also known as bacteriophages, are some of the most numerous entities on earth.

“We chose to study a family of unusually large bacteriophage and to apply cutting edge methods to watch their replication in unprecedented detail,” said Kit Pogliano, a professor of molecular biology who participated in the study.

Joe Pogliano and his colleagues found that shortly after bacteriophages infect bacteria, they destroy much of the existing architecture of the bacterial cells, including bacterial DNA, then hijack the remaining cellular machinery. The viruses then reorganize the entire cell into an efficient, centralized factory to produce the next generation of viruses.

“This factory and the surrounding arrangement of the infected cell are remarkably similar to the organization seen in plant and animal cells,” said Pogliano.

Bacteria lack many of the specialized structures that compartmentalize cellular processes in plant or animal cells, which biologists call “eukaryotic” cells. Bacteria, for example, lack an enclosed nucleus, which contains genetic information and acts as the control center of the cell.

But Vorrapon Chaikeeratisak, a postdoctoral fellow, and Katrina Nguyen, a graduate student in Pogliano’s laboratory, found that invading viruses organize the structures within bacteria to mimic those found in eukaryotic cells.

Using fluorescent microscopy, the two biologists discovered that as viruses replicate within bacterial cells, they build compartments to separate the different processes going on during infection.

“These compartments enclose all the viral DNA, just as a nucleus does in a plant or mammalian cell,” said Chaikeeratisak, the first author of the paper. “DNA processes, like replication or transcription, occur inside the compartment while proteins are produced outside the compartment.”

Elizabeth Villa, a professor of chemistry and biochemistry at UC San Diego, and David Agard, a professor of biochemistry and biophysics at UC San Francisco, used a specialized technique, called “cryo-electron tomography,” to produce images of the processes that Chaikeeratisak and Nguyen initially discovered at extremely high magnification.

Those pictures showed viral offspring being assembled around the nucleus-like compartment in the bacterium. Eventually, these new viruses burst the cell open and spread out to infect neighboring cells.

“These observations of viral manipulation of a cell are completely unexpected, as no bacterial virus has been seen to reorganize a cell in so drastic a manner,” said Pogliano. “The restructuring of a simple cell to resemble an existing, more complicated system blurs the line between simple bacterial cells and those of ‘higher’ organisms, such as plants and animals.”

Could this be how multicellular organisms evolved? One existing theory, called “viral eukaryogenesis,” suggests that the first eukaryotic cell was created when a large virus took over a bacterium. Eventually, the bacterium and virus formed a compound cell, in which the virus evolved into the nucleus.

“It may be too early to know if this particular virus is an intermediate step in the transition from bacteria and viruses to multicellular eukaryotes, but this discovery could broaden knowledge about the origins of life as we know it,” said Pogliano.

Source: UC San Diego

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New Theory for Explaining the Function of Proteins

A University of Arkansas chemist and his collaborator at North Carolina State University have developed a new theory for explaining how proteins and other biomolecules function based on movement and change of shape and structure rather than content.

Proteins are considered the workhorse molecules of cells. They are responsible for nearly all tasks in cellular life, including product manufacture, waste cleanup and routine maintenance. For example, some proteins are responsible for transport of materials and information between the cell and its environment, a vital task for the survival and normal function of the cell. Any disorder in protein function could result in disease, and the study of protein function is necessary for understanding the molecular basis of disease.

Open and closed forms of channel proteins, which function by changing their shape. Illustration provided by the researcher

“To function, proteins change their shape,” said Mahmoud Moradi, assistant professor of chemistry and biochemistry in the J. William Fulbright College of Arts and Sciences. “Because proteins are not static objects, understanding their conformational dynamics is a necessary step in deciphering the molecular mechanisms underlying their function. The study of protein dynamics is therefore important for understanding the molecular basis of the disease and establishing a ‘rational design’ for developing more efficient drugs.”

The theory developed by Moradi and Ashkan Fakharzadeh, a graduate student North Carolina State University, describes and simulates the way proteins and other biomolecules change their shape to function.

“Conventional theories of protein dynamics ignore the curved nature of the configurational space of biomolecules,” Moradi said. “In this work, we have developed an innovative formalism that relies a geometric theory, traditionally used in general relativity and similar fields, to modify theories of protein dynamics.”

Moradi and Fakharzadeh will address two interrelated questions to further develop their theory: How do proteins function by changing their conformation and by undergoing concerted motions, and how can these conformational changes be simulated at an atomic level? Answering these questions would shed light on the structure-function relationships in proteins, Moradi said, and could improve scientists’ understanding of diseases at a molecular level.

Source: University of Arkansas

New Technology Will Cut Plug-in Hybrid Fuel Consumption by One Third

Engineers at the University of California, Riverside have taken inspiration from biological evolution and the energy savings garnered by birds flying in formation to improve the efficiency of plug-in hybrid electric vehicles (PHEVs) by more than 30 percent.

Xuewei Qi and a team of UCR researchers are using vehicle connectivity and evolutionary algorithms to improve the efficiency of Plug-In Hybrid Electric Vehicles.

Titled “Development and Evaluation of an Evolutionary Algorithm-Based Online Energy Management System for Plug-In Hybrid Electric Vehicles,” a paper describing the research was recently accepted for publication in the journal IEEE Transactions on Intelligent Transportation Systems. The work was led by Xuewei Qi, a postdoctoral researcher at the Center for Environmental Research and Technology (CE-CERT) in UCR’s Bourns College of Engineering, and Matthew Barth, CE-CERT director and a professor of electrical and computer engineering at UCR.

PHEVs, which combine a gas or diesel engine with an electric motor and a large rechargeable battery, offer advantages over conventional hybrids because they can be charged using mains electricity, which reduces their need for fuel. However, the race to improve the efficiency of current PHEVs is limited by shortfalls in their energy management systems (EMS), which control the power split between engine and battery when they switch from all-electric mode to hybrid mode.

While not all plug-in hybrids work the same way, most models start in all-electric mode, running on electricity until their battery packs are depleted, then switch to hybrid mode. Known as binary mode control, this EMS strategy is easy to apply, but isn’t the most efficient way to combine the two power sources. In lab tests, blended discharge strategies, in which power from the battery is used throughout the trip, have proven more efficient at minimizing fuel consumption and emissions. However, their development is complex and, until now, they have required an unrealistic amount of information upfront.

“In reality, drivers may switch routes, traffic can be unpredictable, and road conditions may change, meaning that the EMS must source that information in real-time,” Qi said.

The highly efficient EMS developed and simulated by Qi and his team combines vehicle connectivity information (such as cellular networks and crowdsourcing platforms) and evolutionary algorithms—a mathematical way to describe natural phenomena such as evolution, insect swarming and bird flocking.

“By mathematically modeling the energy saving processes that occur in nature, scientists have created algorithms that can be used to solve optimization problems in engineering,” Qi said. “We combined this approach with connected vehicle technology to achieve energy savings of more than 30 percent. We achieved this by considering the charging opportunities during the trip—something that is not possible with existing EMS.”

The current paper builds on previous work by the team showing that individual vehicles can learn how to save fuel from their own historical driving records. Together with the application of evolutionary algorithms, vehicles will not only learn and optimize their own energy efficiency, but will also share their knowledge with other vehicles in the same traffic network through connected vehicle technology.

“Even more importantly, the PHEV energy management system will no longer be a static device—it will actively evolve and improve for its entire life cycle. Our goal is to revolutionize the PHEV EMS to achieve even greater fuel savings and emission reductions,” Qi said.

The work was done by Qi and Barth, together with Guoyuan Wu, assistant research engineer at CE-CERT, and Kanok Boriboonsomsin, associate research engineer at CE-CERT. This project was supported in part by the National Center for Sustainable Transportation.

Source: UC Riverside

Chemistry on the Edge: Study Pinpoints Most Active Areas of Reactions on Nanoscale Particles

Defects and jagged surfaces at the edges of nanosized platinum and gold particles are key hot spots for chemical reactivity, a team of researchers working at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the Hebrew University of Jerusalem in Israel confirmed with a unique infrared probe.

This illustration shows the setup for an experiment at Berkeley Lab’s Advanced Light Source that used infrared light (shown in red) and an atomic force microscope (middle and top) to study the local surface chemistry on coated platinum particles (yellow) measuring about 100 nanometers in length. Image credit: Hebrew University of Jerusalem

Experiments like this should help researchers to customize the structural properties of catalysts to make them more effective in fostering chemical reactions.

The study, published Jan. 11 in Nature, is an important step in chronicling how the atomic structure of nanoparticles impacts their function as catalysts in chemical reactions. Catalysts, which play a role in the production of many industrial products, such as fertilizers, fuel, and plastics, are materials that can speed up chemical reactions and make them more efficient while remaining unchanged in the process.

Scientists have known that materials can behave differently at the nanoscale than they do in larger quantities, and that customizing their size and shape can enhance their properties for specific uses. This new technique pinpointed the areas on single metallic particles—which measure about 100 nanometers (100 billionths of a meter)—that are most active in chemical reactions.

From a collection of nanoscale platinum particles, left, researchers homed in on the chemistry occurring in different surface areas of individual nanoscale platinum particles like the one at right, which measures about 100 billionths of an inch across. Researchers found that chemical reactivity is concentrated at the edges of the particles (red circle at right), with lesser activity in the central area (black circle). This image was produced by an atomic force microscope. Image credit: “High-spatial-resolution mapping of catalytic reactions on single particles,” Nature, Jan. 11, 2017

Researchers combined a broad spectrum of infrared light, produced by Berkeley Lab’s Advanced Light Source (ALS), with an atomic force microscope to reveal different levels of chemical reactivity at the edges of single platinum and gold nanoparticles compared to their smooth, flat surfaces.

They used a unique capability at ALS, dubbed SINS (for synchrotron-radiation-based infrared nanospectroscopy), to explore the detailed chemistry occurring on the surface of the particles, and achieved resolution down to 25 nanometers.

“It allows you to see all of this interplay in chemistry,” said Michael Martin, a senior staff scientist in charge of infrared beamlines at the ALS. “That’s what makes this special.”

Hans Bechtel, a research scientist at Berkeley Lab who works at the ALS infrared beamlines, added, “You can simultaneously see reactants and the products formed in reactions.”

Surface chemistry on nanosized gold particles, shown here at low-magnification, left, and high-magnification, right, in images produced with a scanning electron microscope, was studied with infrared light produced by Berkeley Lab’s Advanced Light Source. The scale bar at left represents 5 microns, or 5 millionths of an inch, and the scale bar at right represents 1 micron. Image credit: “High-spatial-resolution mapping of catalytic reactions on single particles,” Nature, Jan. 11, 2017

In the experiment, researchers coated the metallic particles with a layer of reactive molecules and focused the ALS-produced infrared light onto the tiny tip (25 nanometers in its diameter) of the atomic force microscope.

The microscope’s tip, when coupled with the highly focused infrared light, worked like an extremely sensitive antenna to map the surface structure of individual nanoparticles while also revealing their detailed surface chemistry.

“We were able to see the exact fingerprint of molecules on the surface of the particles and validate a well-known hypothesis in the field of catalysis,” said Elad Gross, a faculty member at the Institute of Chemistry and the Center for Nanoscience and Nanotechnology at the Hebrew University of Jerusalem, who led the study along with F. Dean Toste, a faculty scientist in the Chemical Sciences Division at Berkeley Lab and professor in UC Berkeley’s Department of Chemistry.

Knowing the precise level of energy that’s needed to trigger chemical reactions (the activation energy) is key in optimizing reactions, and can reduce costs at the industrial scale by conserving energy use.

“This technique has the ability to tell you not only where and when a reaction occurred, but also to determine the activation energy for the reaction at different sites,” Gross said. “What you have here is a tool that can address fundamental questions in catalysis research. We showed that areas which are highly defective at the atomic level are more active than smooth surfaces.”

This characteristic relates to the small size of the particles, Gross noted. “As the particle size is decreased, the structure is less uniform and you have more defects,” he said.

Smaller particles have higher surface area per particle than larger particles, which means that more atoms will be located at the edges. Atoms at the edges of the particles have fewer neighbors than those along its smooth surfaces, and fewer neighbors means more freedom to participate in chemistry with other elements.

As the studied chemical reactions occur very rapidly—in less than a second—and the ALS technique can take about 20 minutes to scan a single spot on a particle, the researchers used a layer of chemically active molecules, which were attached to the surface of the particle, as markers for the catalytic reactivity.

The catalytic reaction in the study was analogous to what occurs in gasoline-powered vehicles’ catalytic converters. Catalytic converters use platinum particles and other materials to convert car exhaust into less-toxic emissions.

Future experiments planned using the SINS technique will focus on documenting active chemical processes that use controlled flows of gases or liquids to trigger reactions, researchers said, and future experiments may use varying pressure and temperature to gauge effects.

“I think this is going to be a very interesting tool for further experiments and analyses that can answer a lot of questions that couldn’t be answered before,” Gross said. “This tool gives us the capability to get better resolution by three orders of magnitude than some other techniques, which has opened a very wide field for catalysis and surface-chemistry studies.”

Future studies could also conceivably combine infrared- and X-ray-based methods at the ALS to gather richer chemical information, researchers said. There are already plans for a new infrared beamline at the ALS that will increase the capacity and capabilities for infrared chemical studies and also launch infrared-based 3-D structural studies at the ALS.

The ALS is a DOE Office of Science User Facility. This work was supported by the DOE Office of Science.

Source: LBL

Captured on Video: DNA Nanotubes Build a Bridge Between Two Molecular Posts

In a microscopic feat that resembled a high-wire circus act, Johns Hopkins researchers have coaxed DNA nanotubes to assemble themselves into bridge-like structures arched between two molecular landmarks on the surface of a lab dish.

Time-lapse movie showing the formation of a DNA nanotube bridge (green) between two molecular landmarks (red and blue) that are separated by 6 microns. The movie is 5,000 times sped up with respect to real time. Image credit: Nature Nanotechnology, 2016, Abdul M. Mohammed, et. al.

The team captured examples of this unusual nanoscale performance on video.

This self-assembling bridge process, which may someday be used to connect electronic medical devices to living cells, was reported by the team recently in the journal Nature Nanotechnology.

To describe this process, senior author Rebecca Schulman, an assistant professor of chemical and biomolecular engineering in the university’s Whiting School of Engineering, referred to a death-defying stunt shown in the movie “Man on Wire.” The film depicted Philippe Petit’s 1974 high-wire walk between the World Trade Center’s Twin Towers.

Schulman pointed out that the real-life crossing could not have been accomplished without a critical piece of old-fashioned engineering: Petit’s hidden partner used a bow and arrow to launch the wire across the chasm between the towers, allowing it to be secured to each structure.

“A feat like that was hard to do on a human scale,” Schulman said. “Could we ask molecules to do the same thing? Could we get molecules to build a ‘bridge’ between other molecules or landmarks on existing structures?”

The paper’s lead author, Abdul Mohammed, a postdoctoral fellow in Schulman’s lab, used another analogy to describe the molecular bridge-building feat they demonstrated at the nanoscale level. “If this process were to happen at the human scale,” Mohammed said, “it would be like one person casting a fishing line from one side of a football field and trying to hook a person standing on the other side.”

To accomplish this task, the researchers turned to DNA nanotubes. These microscopic building blocks, formed by short sequences of synthetic DNA, have become popular materials in the emerging nanotechnology construction field. The sequences are particularly useful because of their ability to assemble themselves into long, tube-like structures known as DNA nanotubes.

In the Johns Hopkins study, these building blocks attached themselves to separate molecular anchor posts, representing where the connecting bridge would begin and end. The segments formed two nanotube chains, each one extending away from its anchor post. Then, like spaghetti in a pot of boiling water, the lengthening nanotube chains wriggled about, exploring their surroundings in a random fashion. Eventually, this movement allowed the ends of the two separate nanotube strands to make contact with one another and snap together to form a single connecting bridge span.

To learn more about how this process occurs, the researchers used microscopes to watch the nanotubes link to their molecular landmarks, which were labeled with different colored fluorescent dyes and attached to transparent glass. The team’s video equipment also captured the formation of nanotubes spans, as the two bridge segments lengthened and ultimately connected. Completion of each nanoscale bridge in the accompanying example took about six hours, but the team’s videos were sped up significantly to enable a more rapid review. Depending on how far apart the molecular anchor posts were located, the connection process took anywhere from several hours to two days.

The ability to assemble these bridges, the researchers say, suggests a new way to build medical devices that use wires, channels or other devices that could “plug in” to molecules on a cell’s surface. Such technologies could be used to understand nerve cell communication or to deliver therapeutics with unprecedented precision. Molecular bridge-building, the researchers said, is also a step toward building networked devices and “cities” at the nanoscale, enabling new components of a machine or factory to communicate with one another.

Source: NSF, Johns Hopkins University