Research Highlights and New Publications-Spring 2009

Nov 25, 2009
David LeBard and Dmitry Matyushov investigate bacterial photosynthesis via numerical simulations and theoretical calculations

It has long been appreciated that the ability of proteins to participate effectively in the energetic chains of biology is linked to the electrostatics of proteins themselves and the hydration shells of water. The standard textbook description of the local protein polarity ascribes it a low dielectric constant comparable to that of chloroform. Simulations performed by Matyushov's group show that this is only partially true. Proteins have a broad distribution of relaxation times and, depending on the process of interest, can be either non-polar or very polar. This feature of polarity switch directly applies to the energetics of bacterial photosynthesis where charge separation reactions occur on short, picosecond times revealing non-polar protein environment while recombination reactions occur on the longer, nanosecond times switching to a strongly polar response of the protein. This latter polar response is characterized by a significantly non-Gaussian statistics of the electrostatic fluctuations. This property, directly observed in MD simulations, can potentially explain how nature performs multiple hops of electrons in its energy chains without loosing all the input energy initiated by either the incoming photon or a redox reaction. The non-Gaussian character of the electrostatic fluctuations, linked to a particular structure of water's hydration shells around proteins, allows an order of magnitude increase in the energetic efficiency of interprotein electron hops compared to the standard picture of Gaussian electrostatic fluctuations developed for small redox molecules.

"Energetics of Bacterial Photosynthesis", David N. LeBard and Dmitry V. Matyushov, J. Phys. Chem. B 2009, 113, 12424–12437

Nov 12, 2009
Mark Hayes and colleagues are developing more efficient biochemical sensors

A team of ASU researchers aim to improve patient outcomes for stroke and heart attack by developing a faster and more sensitive sensor platform to detect the molecules released into the bloodstream from these episodes. The team is producing a more detailed, accurate and precise diagnostic and risk stratification, providing better care (such as pharmaceuticals, treatments options, and timing of treatments) and avoiding unnecessary and costly actions.

Currently, heart attack or acute myocardial infarction (MI), a deadly short-term condition where an obstruction hinders blood flow and oxygen delivery to the heart causing tissue death, is diagnosed with electrocardiogram (ECG) with only 60% sensitivity. Biomarkers used to confirm diagnosis take hours to assay and the early molecular indicators are at very low concentrations preventing universal usefulness. Accurate and early diagnosis is key because reperfusion therapy is exponentially more effective the earlier it is administered.

Stroke is a general term that applies to multiple types of cerebrovascular disorders relating to either the loss of blood flow (infarction) or bleeding (hemorrhage or aneurysm). A key challenge is to identify which of these are occurring-and quickly, because recombinant tissue plasminogen activator (TPA) significantly reduced the morbidity and mortality of patients with cerebral infarction, but must be administered within 3 hours of symptomatic onset-however and very importantly, TPA can be devastating to a patient with hemorrhagic stroke. Limitations in current diagnostics via CT and MRI scans and classic neurologic assessments result in less than 2% of patients with infarct stroke actually receiving TPA even though up to 60% of patients arrive in an emergency department within three hours of stroke onset.

Working from a collaboration established while Dr. Karl Booksh was a colleague at ASU, Mark Hayes is helping to develop these improved diagnostics. The National Institute of Biomedical Imaging and Bioengineering of the NIH is supporting the work with a $0.5M two year grant. The grant is centered on developing new sample isolation, purification and concentration strategies pioneered in the Hayes laboratory combined with ultra small volume and sensitive detection schemes based on surface plasmon resonance developed in Dr. Booksh's laboratory.

The team is developing assays for myoglobin and cardiac troponin I (cTnl) as MI biomarkers. These will be monitored in 200 microliter samples and only take a few minutes to provide fast turnaround for sequential monitoring. Detection limits will be at or below current 'high sensitivity' assay levels to provide the earliest possible confirmed diagnosis. With these assays, the change in the concentration of myoglobin and cTnl are the key features in providing an early confirmed diagnosis-inferring these proposed assays need to be sensitive and precise. In the case of myoglobin, MI cannot be discounted if serum myoglobin is above~5 nM (85 ng/mL). However, some MI victims do not reach these levels until several hours after the infarction, with a peak at approximately five hours. Furthermore, other MI patients do not display serum myoglobin concentrations over set threshold, leading to false negative diagnoses. Studies suggest that misdiagnosis of MI could be prevented by examining serial measurements of serum myoglobin combined with sensitivity well below 5 nM, well within reach of our proposed technology. A panel for stroke will include: glial fibrillary acidic protein (GFAP) and S100, NSE marker of nerve damage, matrix metalloproteinase-9 (MMP9) is a marker of inflammation, the von Willebrand factor (vWF) is a marker of thrombosis. Cardiac-reactive protein has recently been shown as diagnostic is strokes as well as with MI.

"Insulator-based dielectrophoretic separation of small particles in a sawtooth channel", Kang Pang Chen* J. R. Pacheco, M. A. Hayes, S. J. R. Staton Electrophoresis 2009, 30, 1441-1448.

"Electrophoretic Exclusion for the Selective Transport of Small Molecules", Michelle M. Meighan, Michael W. Keebaugh, Alicia M. Quihuis, Stacy M. Kenyon, and Mark A. Hayes* Electrophoresis 2009, 30, 3786-3792.  

Beneath the red-weathered and spinifex covered hills of Western Australia, drill core collected of 2.5 billion-year-old shales revealed evidence for early sulfidic conditions in the ocean and photosynthetic oxygen in the atmosphere. Photo Ariel Anbar

Oct 29, 2009
Ariel Anbar and colleagues discover a new wrinkle in ancient ocean chemistry

ASU researcher leads overall effort (total of four papers in Science), and reports on the fact that oxygen production began in the Earth's oceans at least 100 million years before oxygen accumulated in the atmosphere.

Scientists widely accept that around 2.4 billion years ago, the Earth's atmosphere underwent a dramatic change when oxygen levels rose sharply. Called the "Great Oxidation Event" (GOE), the oxygen spike marks an important milestone in Earth's history, the transformation from an oxygen-poor atmosphere to an oxygen-rich one, paving the way for complex life to develop on the planet.

Two questions that remain unresolved in studies of the early Earth are when oxygen production via photosynthesis got started and when it began to alter the chemistry of Earth's ocean and atmosphere.

ASU scientists, working with collaborators at other institutions, have been pursuing these questions in a series of studies of ancient rocks from Western Australia. The latest of these studies appears in the Oct. 30 issue of Science.

The new findings corroborate previous results that oxygen production began in Earth's oceans at least 100 million years before the GOE, but also go a step further in demonstrating that even very low concentrations of oxygen can have profound effects on ocean chemistry. This research was led by geoscientists at the University of California, Riverside (UCR), working with Ariel Anbar, a professor in the department of Chemistry and Biochemistry and the School of Earth and Space Exploration in the College of Liberal Arts and Sciences at ASU.

To arrive at their results, the researchers analyzed 2.5 billion-year-old black shales from Western Australia. Essentially representing fossilized pieces of the ancient seafloor, the fine layers within the rocks allowed the researchers to page through ocean chemistry's evolving history. These rocks were obtained under the leadership of Anbar, with support from the NASA Astrobiology Institute of which ASU is a member.

Specifically, the shales revealed that episodes of hydrogen sulfide accumulation in the oxygen-free deep ocean occurred nearly 100 million years before the GOE and up to 700 million years earlier than such conditions were predicted by past models for the early ocean. Scientists have long believed that the early ocean, for more than half of Earth's 4.6 billion-year history, was characterized instead by high amounts of dissolved iron under conditions of essentially no oxygen.

"The conventional wisdom has been that appreciable atmospheric oxygen is needed for sulfidic conditions to develop in the ocean," said Chris Reinhard, a Ph.D. graduate student in the Department of Earth Sciences at UCR and and lead author of the research paper. "We found, however, that sulfidic conditions in the ocean are possible even when there is very little oxygen around, below about 1/100,000th of the oxygen in the modern atmosphere."

Reinhard explained that at even very low oxygen levels in the atmosphere, the mineral pyrite can weather on the continents, resulting in the delivery of sulfate to the ocean by rivers. Sulfate is the key ingredient in hydrogen sulfide formation in the ocean.

Timothy Lyons, a professor of biogeochemistry at UCR, whose laboratory led the research, explained that the hydrogen sulfide in the ocean is a fingerprint of photosynthetic production of oxygen 2.5 billion years ago.

"A pre-GOE emergence for oxygenic photosynthesis is a matter of intense debate, and its resolution lies at the heart of understanding the evolution of diverse forms of life," he said. "We have found an important piece of that puzzle."

"These data don't make much sense unless there were at least small amounts of oxygen in the environment. The simplest explanation is oxygen-producing photosynthesis long before concentrations of oxygen in the atmosphere were even a tiny fraction of what they are today," said Anbar, a co-author of the research paper. "The results are beautifully consistent with our previous results. The story just gets stronger and stronger the more we look at these ancient sediments."

The researchers argue that the presence of small amounts of oxygen may have stimulated the early evolution of eukaryotes - organisms whose cells bear nuclei - millions of years prior to the GOE.

"This initial oxygen production set the stage for the development of animals almost two billion years later," Lyons said. "The evolution of eukaryotes had to take place first."

The findings also have implications for the search for life on extrasolar planets.

"Our findings add to growing evidence suggesting that biological production of oxygen is a necessary but not sufficient condition for the evolution of complex life," Reinhard said. "A planetary atmosphere with abundant oxygen would provide a very promising biosignature. But one of the lessons here is that just because spectroscopic measurements don't detect oxygen in the atmosphere of another planet doesn't necessarily mean that no biological oxygen production is taking place." Anbar, Reinhard, and Lyons were joined in the research by Clint Scott of UCR and Rob Raiswell of the University of Leeds, United Kingdom. The two-year study was supported by the National Science Foundation and NASA.

Media contacts:
Jenny Green, (480) 965-1430; jenny.green@asu.edu
Iqbal Pittalwala, UC-Riverside (951) 827-6050; iqbal@ucr.edu
Cheryl Dybas, NSF (703) 292-7734 cdybas@nsf.gov

Oct 12, 2009
Jim Allen and colleagues study the interaction of spinach nitrite reductase with ferredoxin

A series of site-directed mutants of the ferredoxin-dependent spinach nitrite reductase has been characterized and several amino acids have been identified that appear to be involved in the interaction of the enzyme with ferredoxin. Ferredoxins are acidic, low molecular weight, soluble iron-sulfur proteins found in various organisms, and act as multifuncitonal electron carriers in diverse redox systems. Iron-sulfur proteins are defined as proteins carrying iron-sulfur cluster(s) in which the iron is at least partially coordinated by sulfur. Iron-sulfur clusters are prosthetic groups commonly found in various proteins that participate in oxidation-reduction reactions and catalysis.

In a complementary study, binding constants to nitrite reductase and steady-state kinetic parameters of site-directed mutants of ferredoxin were determined in an attempt to identify ferredoxin amino acids involved in the interaction with nitrite reductase. The results have been interpreted in terms of an in-silico docking model for the 1:1 complex of ferredoxin with nitrite reductase.

"The Interaction of Spinach Nitrite Reductase with Ferredoxin: A Site-Directed Mutation Study", Masakazu Hirasawa, Jatindra N. Tripathy, Ramasamy Somasundaram, Michael K. Johnson, Megha Bhalla, James P. Allen, and David B. Knaff, Mol Plant, May 2009; 2: 407 - 415.

Link to the full article

Sep 23, 2009
John Chaput, Jim Allen and colleagues discover an interesting twist on the emergence of early protein enzymes...

How primitive enzymes emerged from a primordial pool remains a fundamental unanswered question with important practical implications in synthetic biology. Chaput and colleagues show that a de novo evolved ATP binding protein, selected solely on the basis of its ability to bind ATP, mediates the regiospecific hydrolysis of ATP to ADP when crystallized with 1 equiv of ATP. Structural insights into this reaction were obtained by growing protein crystals under saturating ATP conditions. The resulting crystal structure refined to 1.8 Å resolution reveals that this man-made protein binds ATP in an unusual bent conformation that is metal-independent and held in place by a key bridging water molecule. Removal of this interaction using a null mutant results in a variant that binds ATP in a normal linear geometry and is incapable of ATP hydrolysis. Biochemical analysis, including high-resolution mass spectrometry performed on dissolved protein crystals, confirms that the reaction is accelerated in the crystalline environment. This observation suggests that proteins with weak chemical reactivity can emerge from high affinity ligand binding sites and that constrained ligand-binding geometries could have helped to facilitate the emergence of early protein enzymes.  

"A Synthetic Protein Selected for Ligand Binding Affinity Mediates ATP Hydrolysis", Chad R. Simmons, Joshua M. Stomel, Michael D. McConnell, Daniel A. Smith, Jennifer L. Watkins, James P. Allen and John C. Chaput, ACS Chem. Biol., 2009, 4 (8), pp 649 - 658 DOI: 10.1021/cb900109w Publication Date (Web): June 12, 2009

Link to the full article

Haboob in Phoenix, AZ,  A haboob is a very strong dust storm that moves through hot dry regions like Maricopa County.

Sep 8, 2009
Ariel Anbar, Pierre Herkes and Brian Majestic (Dreyfus Postdoctoral Fellow) publish two studies on iron isotope ratios in local atmospheric particles...  

Both papers pertain to using high precision metal isotope measurements to differentiate natural from anthropogenic (pollution) sources. Identification of atmospheric iron is a key parameter in understanding the source of iron in urban and remote areas. Atmospheric deposition of desert dust, which also can include an anthropogenic component, is a primary nutrient source for most of the open ocean. To better assess particulate matter (PM) sources specific to iron, they measured the iron isotopic composition of aerosols in two size fractions. Atmospheric aerosol samples were collected in the U.S. desert Southwest at a mixed suburban/agricultural site near Phoenix (Higley), AZ. Using multiple collector inductively coupled plasma mass spectrometry, they found differences in iron isotopic composition within the PM10 um aerosol.

Their data demonstrate that iron isotope composition can be a valuable tool in the source-apportionment of iron in atmospheric particles. Their results were published in the premier American Chemical Society (ACS) journal for environmental chemistry.

"Stable Isotopes as a Tool to Apportion Atmospheric Iron", Brian J. Majestic, Ariel D. Anbar, Pierre Herckes, Environ. Sci. Technol., 2009, 43 (12), pp 4327-4333 DOI: 10.1021/es900023w. Link to the full article

In their second paper trace metal contents and iron isotope composition of size-resolved aerosols were determined in a parking structure in Tempe (Tyler St. at ASU). Particulate matter (PM) < 2.5 µm in diameter (the fine fraction) and PM > 2.5 µm were collected. Several air toxics (e.g., arsenic, cadmium, and antimony) were enriched above the crustal average, implicating automobiles as an important source. Extremely high levels of fine copper (up to 1000 ng m- 3) were also observed in the parking garage, likely from brake wear. The iron isotope composition of the aerosols were found to be + 0.15 ± 0.03'' and + 0.18± 0.03'' for the PM < 2.5 µm and PM > 2.5µm fractions, respectively. The similarity of isotope composition indicates a common source for each size fraction. To better understand the source of iron in the parking garage, the elemental composition in four brake pads (two semi-metallic and two ceramic), two tire tread samples, and two waste oil samples were determined. Striking differences in the metallic and ceramic brake pads were observed. The ceramic brake pads contained 10-20% copper by mass, while the metallic brake pads contained about 70% iron, with very little copper. Both waste oil samples contained significant amounts of calcium, phosphorous, and zinc, consistent with the composition of some engine oil additives.

Differences in iron isotope composition were observed between the source materials; most notably between the tire tread (average = +0.02'') and the ceramic brake linings (average = + 0.65''). Differences in isotopic composition were also observed between the metallic (average = +0.18") and ceramic brake pads, implying that iron isotope composition may be used to resolve these sources. The iron isotope composition of the metallic brake pads was found to be identical to the aerosols, implying that brake dust is the dominant source of iron in a parking garage.

"Elemental and iron isotopic composition of aerosols collected in a parking structure", Brian J. Majestic, Ariel D. Anbar, Pierre Herckes, Science of The Total Environment, 407 (2009) 5104–5109. Link to the full article

Aug 25, 2009
Marcia Levitus and coworkers publish: Photophysics of Backbone Fluorescent DNA Modifications: Reducing Uncertainties in FRET

Fluorescence Resonance Energy Transfer (FRET) is a spectroscopic technique widely used to investigate the structure and dynamics of biomolecules, including proteins and nucleic acids (DNA, RNA). The technique relies on the interaction between the electronic excited states of two molecules: a donor, which is directly excited by a laser or lamp, and an acceptor, which is excited indirectly when part of the excitation energy of the donor is transferred to the acceptor through nonradiative dipole-dipole coupling. The efficiency of this process depends strongly on the distance between the donor and acceptor molecules. If the two fluorophores are far apart (~>10 nm), the interactions are so weak that the donor retains its native fluorescence properties. However as the donor-acceptor distance decreases, these interactions become more efficient resulting in a lower population of donor excited states, and a greater population of acceptor excited states. A consequence of this is that the fluorescence intensity (the 'brightness') of the donor decreases (i.e. it becomes dimmer), and the fluorescence intensity of the acceptor increases. The relative fluorescence intensities of the donor and acceptor are therefore related to the distance between the two molecules, providing a means by which distances can be measured at the molecular level. These distances can give insight into the structure of biomolecules, and more interestingly into their dynamics during biological activity. It is now possible to measure the time-dependent FRET signal of a single biomolecule, providing a unique insight into the real-time dynamics of biomolecules that is not accessible by other techniques.

Due to its capability to measure molecular distances, FRET is usually referred to as a 'molecular ruler'. The idea behind this analogy is that the measurement of the fluorescence intensities of both the donor and acceptor molecules, which determines the efficiency of FRET, is equivalent to using a ruler in the nanometer-length scale. However, things are not that simple. The interaction between the electronic states of the two fluorophores depends not only on distance, but also on the orientation of the two molecules and other spectroscopic properties of the dyes. As a consequence, in reality FRET is a ruler with fuzzy tick marks, and precise measurements are practically impossible.

Why is it so hard to know the orientation of the fluorophores? The answer is that biological molecules are rarely fluorescent, so the measurement requires that exogenous fluorescent probes are attached to the points of interest. The chemistry involved in these attachments is such that the fluorophores are separated from the protein or DNA molecule by long flexible linkers. In the past, researchers have assumed that these linkers are long enough so that they provide enough rotational freedom so the orientation factor is averaged out. For this to be true, the molecules need to rotate fast in the few nanoseconds in which the FRET interaction takes place, so they basically 'see each other' from any possible orientation. However, in this paper and in previous work, we used time-resolved fluorescence anisotropy measurements to show that this is not true. The fluorophores rotate only partially in this time-scale, so the interaction occurs from completely unknown orientations. This turns out to be an important contribution to the 'fuzziness' of the tick marks of the ruler, which has not been addressed properly in a huge number of studies.

But orientation is not the only problem. Linkers are long enough that actually create enough flexibility for the dyes to span many positions in space, and even allow the fluorophore to fold back on the macromolecule, so their distance is not well-defined either. Our studies suggest that the fluorescent dyes are partly interacting with the macromolecule, in this case DNA, also altering the spectroscopic properties that influence the translation between efficiency of FRET and distance. So how can we improve the quantitative capabilities of FRET (that is create a ruler with more defined tick marks)? This is the question we addressed in this paper. Over the years, scientists chose flexible linkers with the hope of randomizing the orientation of the fluorophores and keeping them far from the macromolecule to avoid interactions that can alter their spectroscopic properties. However, we demonstrated that the linkers do not have enough flexibility to provide fast randomization, but are flexible enough to allow for dye-macromolecule interactions creating uncertainties in orientation, distance, and spectroscopic properties. Therefore, we hypothesized that most of these issues would be resolved, or at least greatly minimized, by doing just the opposite. In this paper, we investigated the properties of the Cy3-Cy5 FRET pair on DNA using a novel chemistry in which the dyes are attached covalently to the backbone of the oligonucleotide minimizing their rotational freedom (see figure). These dyes are among the most popular fluorescent dyes in biochemical and biophysical applications, and we chose DNA because of its relevance to other projects in my lab. We demonstrated that these fluorophores have very little rotational freedom, so their relative distance is better-defined. More importantly, the helical architecture of the DNA molecule determines the orientation of the dyes, greatly reducing the uncertainties related to not knowing how the dyes are oriented relative to each other. To test this, we designed a series of constructs containing a Cy3 and Cy5 molecule attached covalently to the backbone of the DNA and separated by different distances. Because of the helical nature of DNA, the dyes are expected to be collinear if they are separated by an integer number of helical turns. This is important because this is the most efficient orientation for energy transfer: at the same distance, FRET will much more efficient for collinear molecules than for any other orientation.

In the most dramatic case we investigated, the fluorophores were separated by three helical turns of DNA (10.2 nm). These fluorophores would normally show extremely low efficiencies of energy transfer at this distance, but we measured a significant value proving that the orientation was extremely favorable, as we expected from the fact that their separation was an integer number of helical turns. In fact, our measurement was very close to the theoretical limit predicted for collinear fluorophores.

What are the consequences of this study? First, we have characterized the behavior of the fluorophores attached through flexible linkers, and demonstrated that the common assumptions regarding their rapid randomization in orientation are not justified. If investigators choose to use this type of chemistry, they need to be aware of the fact that their ruler will have fuzzy tick marks. Second, we proposed an alternative probe design that reduces most of the uncertainties in FRET that are a consequence of the use of flexible linkers: unknown orientation, changes in distance and orientation during the timescales relevant for the FRET interaction, and likelihood of dye-DNA interactions that affect the spectroscopic properties of the dyes and create further uncertainties regarding dye location and orientation. Third, not only our ruler has better-defined tick marks, but also we can measure longer distances. The ability to locate the fluorophores in the optimum orientation (that is, collinear to each other) allows us to detect FRET at distances that are normally beyond the accessible ranges for this.

"Photophysics of Backbone Fluorescent DNA Modifications: Reducing Uncertainties in FRET", Suman Ranjit‡§, Kaushik Gurunathan‡§ and Marcia Levitus*§†‡, J. Phys. Chem. B, 2009, 113 (22), pp 7861–7866 DOI: 10.1021/jp810842u Publication Date (Web): March 26, 2009.

‡The Biodesign Institute. , §Department of Chemistry and Biochemistry. , * Author to whom correspondence should be addressed. E-mail: Marcia.levitus@asu.edu., † Department of Physics.

Link to the abstract...

The reactions that convert light to chemical energy happen in a millionth of a millionth of a second, which makes experimental observation extremely challenging. A premier ultrafast laser spectroscopic detection system established at the Biodesign Institute, with the sponsorship of the National Science Foundation, acts like a high-speed motion picture camera. It splits the light spectrum into infinitesimally discrete slivers, allowing the group to capture vast numbers of ultrafast frames from the components of these exceedingly rapid reactions. These frames are then mathematically assembled, allowing the group to make a figurative "movie" of the energy transfer events of photosynthesis.

May 13, 2009

Pliable proteins keep photosynthesis on the light path
Su Lin, Neal Woodbury, Aaron Tufts and James P. Allen publish in the Proceedings of the National Academy of Sciences...

Photosynthesis is a remarkable biological process that supports life on earth. Plants and photosynthetic microbes do so by harvesting light to produce their food, and in the process, also provide vital oxygen for animals and people. Now, a large, international collaboration between Arizona State University, the University of California San Diego and the University of British Columbia, has come up with a surprising twist to photosynthesis by swapping a key metal necessary for turning sunlight into chemical energy.

The team, which includes: ASU scientists Su Lin, Neal Woodbury, Aaron Tufts and James P. Allen; UBC colleagues J. Thomas Beatty, Paul R. Jaschke, Federico I. Rosell and A. Grant Mauk; Mark Paddock, UCSD; Haiyu Wang, Jilin University, China, described their findings in the May 11 early online edition of the Proceedings of the National Academy of Sciences (http://www.pnas.org/content/early/2009/05/12/0812719106.abstract).

The results may enable researchers to explore a deeper understanding of the structure, function, and evolution of photosynthesis reaction centers in photosystems I and II. Of particular interest, are studies that focus on the interaction between chlorophylls and protein, which differs in naturally occurring reaction center variants. The team may also conduct future experiments to understand the metal substitution limitations of the reaction center and track the protein movements that may be occurring in the reaction center that helps to optimize photosynthesis.

Their results may have long-term practical applications for the development of next-generation solar cells, which could, through biomimicry of photosynthesis, greatly boost the energy efficiency compared with current technology. The robustness of the natural system may offer some useful lessons for engineers trying to improve on current technologies, and bring the costs of solar panels down to the average consumer.

Woodbury has proposed that there might be a way to increase the flexibility of the system used in organic solar cells by incorporating solvents that move on a variety of time scales that could "tune" the molecules to work in a wider variety of conditions.

"Electron transfer in the Rhodobacter sphaeroides reaction center assembled with zinc bacteriochlorophyll", Su Lin, Paul R. Jaschke, Haiyu Wanga, Mark Paddock, Aaron Tufts, James P. Allen, Federico I. Rosell, A. Grant Mauke, Neal W. Woodbury, J. Thomas Beatty, PNAS published online before print May 13, 2009, doi:10.1073/pnas.0812719106.

Link to the Abstract

Full story in EurekAlert

April 20, 2009

Unlikely life thriving at Antarctica's Blood Falls
Anbar group analyzes samples...

An unmapped reservoir of briny liquid chemically similar to sea water, but hidden under an inland Antarctic glacier, appears to support microbial life in a cold, dark, oxygen-poor environment- a most unexpected setting to be teeming with life.

The McMurdo Dry Valleys of Antarctica are devoid of animals and complex plants and scientists consider them to be one of the Earth's most extreme deserts. The Valleys receive, on average, only 10 cm (3.93 inches) of snow each year. Despite the lack of precipitation, during the Antarctic summer, temperatures rise just enough for glaciers protruding into the valleys to begin melting. The meltwater forms streams that enter lakes covered by ice that is two-to-three-stories thick.

Even less forgiving are the conditions found below the Taylor Glacier, an outlet glacier of the East Antarctic Ice Sheet in the otherwise ice-free Dry Valleys. The lack of light beneath the glacier makes the process of photosynthesis improbable, causing researchers to wonder how organisms found below the glacier could survive.

The research, which appears in the April 17 issue of Science, suggests that over the past 1.5 million years the microbes adapted to manipulate sulfur and iron compounds to survive. In place of photosynthesis, the microbes converted Fe(III) to Fe(II) to create food and energy.

The study was led by Jill Mikucki, a National Science Foundation-funded researcher at Dartmouth College. Mikucki and a team of researchers based their analysis on samples taken at the ominously, but aptly named Blood Falls, a water-fall-like feature at the edge of the glacier that flows irregularly, but often has a strikingly bright red appearance in stark contrast to the icy background.

The key piece of data supporting the hypothesis that the microbes were in fact surviving by turning Fe(III) to Fe(II) came from samples analyzed by Ariel Anbar, one of the authors of the study and an associate professor at Arizona State University, and researchers in his group, using instruments in the W. M. Keck Laboratory for Environmental Biogeochemistry at ASU.

"We found that the isotopes of Fe(II) in the brines are shifted in a way that is consistent with this microbial process,''said Anbar, who holds joint appointments in the School of Earth and Space Exploration and the Department of Chemistry and Biochemistry in the College of Liberal Arts and Sciences.

Even the earliest explorers noted the massive red stain at the snout of the glacier and speculated as to what may have caused it. Some guessed that red alga was responsible for the bright color.''In fact, the red color is a result of all that Fe(II) produced by bacteria,''said Anbar.''When the Fe(II)-rich water reaches the surface, the Fe(II) reacts with oxygen in the air to make Fe(III) compounds that are sort of like rust. That's the source of the red color.''

The microbes are remarkably similar in nature to species found in marine environments, leading to the conclusion that the populations under the glacier are the remnants of a larger population of microbes that once occupied a fjord or sea that received sunlight. Many of these marine lineages likely declined, while others adapted to the changing conditions when the Taylor Glacier advanced, sealing off the system under a thick ice cap.

In the paper, however, Mikucki and her colleagues argue that the creatures that survive under the Taylor Glacier are both far more exotic and far more adaptable than the early explorers thought.

Because the outflow from the glacier follows no clear pattern, it took a number of years to obtain the samples needed to conduct an analysis. Finally Mikucki obtained a sample of an extremely salty and clear liquid for analysis.

"When I started running the chemical analysis on it, there was no oxygen,''she said.''That was when this got really interesting; it was a real ‘eureka' moment.''

Further genetic analysis suggests that of the relatively small numbers of microorganisms found in the brine,''the majority of these organisms are from marine lineages,''she said.

In other words, microorganisms more similar to those found in an ocean than on land, but capable of surviving without the food and light sources available in the open ocean.

"The salts associated with these features are marine salts, and given the history of marine water in the dry valleys, it made sense that subglacial microbial communities might retain some of their marine heritage,''she added.

This led to the conclusion that the ancestors of the microbes beneath the Taylor Glacier probably lived in the ocean many millions of years ago. When the floor of the Valleys arose more than 1.5 million years ago, a pool of seawater from the fjord that penetrated the area was trapped. The pool was eventually capped by the flow of the glacier.

The briny pond, whatever its size''is a unique sort of time capsule from a period in Earth's history,''Mikucki said.''I don't know of another environment quite like this on Earth.''

Life below the Taylor Glacier may help scientist address questions about life on''Snowball Earth”, the period of geological time when large ice sheets covered the Earth's surface. But it's also a rich laboratory for studying life in other hostile environments, including the subglacial lakes of Antarctica and perhaps even on other icy planets in the solar system such as below the Martian ice caps or in the ice-covered oceans of Jupiter's moon Europa.  

ASU MEDIA CONTACT: Nikki Staab, nstaab@asu.edu 480-727-9329
NSF MEDIA CONTACT: Peter West, pwest@nsf.gov 703-292-7761  

"A Contemporary Microbially Maintained Subglacial Ferrous "Ocean"", Jill A. Mikucki, Ann Pearson,David T. Johnston, Alexandra V. Turchyn, James Farquhar, Daniel P. Schrag, Ariel D. Anbar, John C. Priscu, Peter A. Lee, Science 17 April 2009: Vol. 324. no. 5925, pp. 397 - 400 DOI: 10.1126/science.1167350

Link to the Abstract

April 2, 2009

Scanning tunneling microscopy (STM) helps with DNA sequencing...Stuart Lindsay, Otto Sankey and colleagues have recently published in Nature Nanotechnology...

Hydrogen bonding has a ubiquitous role in electron transport and in molecular recognition, with DNA base pairing being the best-known example. Scanning tunnelling microscope images and measurements of the decay of tunnel current as a molecular junction is pulled apart by the scanning tunnelling microscope tip are sensitive to hydrogen-bonded interactions. Here, Lindsay and coworkers show that these tunnel-decay signals can be used to measure the strength of hydrogen bonding in DNA base pairs. Junctions that are held together by three hydrogen bonds per base pair (for example, guanine-cytosine interactions) are stiffer than junctions held together by two hydrogen bonds per base pair (for example, adenine-thymine interactions). Similar, but less pronounced effects are observed on the approach of the tunnelling probe, implying that attractive forces that depend on hydrogen bonds also have a role in determining the rise of current. These effects provide new mechanisms for making sensors that transduce a molecular recognition event into an electronic signal.

"Tunnelling readout of hydrogen-bonding-based recognition", Shuai Chang, Jin He, Ashley Kibel, Myeong Lee, Otto Sankey, Peiming Zhang& Stuart Lindsay, Nature Nanotechnology. Published online: 22 March 2009 | doi:10.1038/nnano.2009.48

Link to the Abstract
Full story on biodesign website

Mar 17, 2009

CREDIT: K. SUTLIFF/SCIENCE

Allen and Williams' research highlighted in Science...

ORIGINS: On the Origin of Photosynthesis
Mitch Leslie
Science March 2009: Vol. 323. no. 5919, pp. 1286 - 1287

Where would we be without photosynthesis? In the third essay in Science's series in honor of the Year of Darwin, Mitch Leslie details researchers' efforts to piece together how and when organisms first began to harness light's energy.

An excerpt from the article follows...

Biochemists James Allen and JoAnn Williams of Arizona State University, Tempe, and colleagues are working out how a bacterial reaction center could have evolved photosystem II's appetite for electrons. Taking a hands-on approach, they have been tinkering with the reaction center of the purple bacterium Rhodobacter sphaeroides to determine if they can make it more like photosystem II. First they targeted bacterio- chlorophyll, the bacterial version of chlorophyll that's at the core of the reaction center, and altered the number of hydrogen bonds. Adding hydrogen bonds hiked the molecule's greed for electrons, they found. The water-cleaving portion of photosystem II sports four manganese atoms that become oxidized, or lose electrons. So the team equipped the bacterial reaction center with one atom of the metal. In this modified version, the added manganese also underwent oxidation, the researchers reported in 2005. James Allen says that their creations aren't powerful enough to split water. But eventually, they hope to engineer a reaction center that can oxidize less possessive molecules, such as hydrogen peroxide, that would have been present on the early Earth. Even if the researchers never replicate photosystem II, "if we define the intermediate stages, we've accomplished a lot," he says.  

   Link to the full article

Mar 3 , 2009

Gust, Moore and Moore publish in the Chem. Soc. Rev.'s 2009 Renewable Energy issue, reviewing the latest developments in renewable energy research

Biology and technology for photochemical fuel production Michael Hambourger, Gary F. Moore, David M. Kramer, Devens Gust, Ana L. Moore and Thomas A. Moore Sunlight is the ultimate energy source for the vast majority of life on Earth, and organisms have evolved elegant machinery for energy capture and utilization. Solar energy, whether converted to wind, rain, biomass or fossil fuels, is also the primary energy source for human-engineered energy transduction systems. This tutorial review draws parallels between biological and technological energy systems. Aspects of biology that might be advantageously incorporated into emerging technologies are highlighted, as well as ways in which technology might improve upon the principles found in biological systems. Emphasis is placed upon artificial photosynthesis, as well as the use of protonmotive force in biology.

"Biology and technology for photochemical fuel production", Michael Hambourger, Gary F. Moore, David M. Kramer, Devens Gust, Ana L. Moore and Thomas A. Moore, Chem. Soc. Rev., 2009, 38, 25 - 35, DOI: 10.1039/b800582f

Link to Abstract

"Engineered and Artificial Photosynthesis: Human Ingenuity Enters the Game", Devens Gust, David Kramer, Ana Moore , Thomas A. Moore, and Wim Vermaas , MRS BULLETIN, VOLUME 33 • APRIL 2008, p383.

Link to the full article

Feb 17 , 2009

Buseck and Adachi publish in a special issue of Elements on nanoparticles in the environment ...

The most continuous and intimate contact the average person has with nanoparticles is almost surely through the air, which is replete with them. Nanoparticles are being generated continuously and in large numbers by vehicles and industries in urban areas and by vegetation and sea spray in rural areas. Volcanoes are sporadic sources of huge numbers. Nanoparticles have large surface area to volume ratios and react rapidly in the atmosphere, commonly growing into particles large enough to interact with radiation and to have serious consequences for visibility and local, regional, and global climate. They also have potentially significant health effects.

The figure on the right shows nanoparticles from biomass burning. Also a photograph of a region of biomass burning, taken near Mexico City (top left). Gases emitted from the fires cooled rapidly and condensed or accumulated as nanoparticles. A low- magnification transmission electron micrograph is shown (bottom left) of biomass-burning particles collected from an airplane and deposited on a substrate of lacey carbon (fibers). This is enlarged to the right and shows nanoparticles trapped within a larger organic particle and therefore observable (red arrows). Other aerosol particles are indicated by white arrows. The compositions were determined using energy dispersive X-ray spectrometry. The sample was collected from aircraft during an international atmospheric campaign called MILAGRO, sponsored by NSF, NASA, DOE, and various other national and international agencies as part of a program to study emissions from tropical megacities. The photo was taken by Kouji Adachi.

"Nanoparticles in the atmosphere", P.R. Buseck and K. Adachi,Elements 4, 389-394, 2008.

Link to Abstract

Jan 31, 2009

Byrne and Angell publish article on biomolecules "out of water"...

In a contribution currently in press Chemical Communications, Nolene Byrne and Austen Angell give another example how use of protic ionic liquid solvents for biomolecule studies can produce interesting phenomena. Although there is only one molecule of water for every two ions present in these solvents, the dissolved proteins behave in many cases as if they are in normal aqueous buffer - except that they seem to be more stable against aggregation. In the present communication these authors show that, also as in aqueous solutions, change of solution conditions to more acidic states can lead to fibril formation. These are the same sort of amyloid fibril that cause Parkinson's and Jacob Kreutz "folding" diseases. However, now, with the right choice of ionic liquids, the fibrils can be readily redissolved. The authors even show that in some cases, most of the original bioactivity can be restored. 

"Formation and dissolution of hen egg white lysozyme amyloid fibrils in protic ionic liquids", Nolene Byrne and C. Austen Angell, Chem. Commun., 2009, 1046

Link to abstract

Jan 6, 2009

Movie showing the 3D architecture of nanotubes formed with 5 nm and 10 nm AuNPs (gold particles). Play Video

Hao Yan and Yan Liu's group publish in this week's Science on the self-assembly of DNA tubules...

DNA tubes are known to form through either self-association of multi-helix DNA bundle structures or closing up of 2D DNA tile lattices. By the attachment of single-stranded DNA to gold nanoparticles, nanotubes of various 3D architectures can form, ranging in shape from stacked rings to single spirals, double spirals, and nested spirals. The nanoparticles are active elements that control the preference for specific tube conformations through size-dependent steric repulsion effects. For example, one can control the tube assembly to favor stacked-ring structures using 10-nanometer gold nanoparticles. Electron tomography reveals a left-handed chirality in the spiral tubes, double-wall tube features, and conformational transitions between tubes.

The future of the nanotechnology field depends on our ability to reliably and reproducibly assemble nanoparticles into 3D structures we can use to develop new technologies. According to Hao Yan and Yan Liu at Arizona State University, the greatest challenges in this burgeoning field include control over nanoscale 3D structure and imaging these tiny materials.

"Control of Self-Assembly of DNA Tubules Through Integration of Gold Nanoparticles", Jaswinder Sharma, Rahul Chhabra, Anchi Cheng, Jonathan Brownell, Yan Liu, and Hao Yan Science 2 January 2009: 112-116.

Link to Abstract

Research Highlights and New Publications-2008

Dec 8, 2008

Professor Anbar 'follows the elements' to understand evolution in ancient oceans...

TEMPE, Ariz. - In the search for life beyond Earth, scientists 'follow the water' to find places that might be hospitable. However, every home gardener knows that plants need more than water, or even sunshine. They also need fertilizer - a mixture of chemical elements that are the building blocks of the molecules of life. Scientists at Arizona State University are studying how the distribution of these elements on Earth - or beyond - shapes the distribution of life, the state of the environment and the course of evolution.

Ariel Anbar, a professor in ASU's Department of Chemistry and Biochemistry and the School of Earth and Space Exploration in the College of Liberal Arts and Sciences weaves together threads from geoscience, chemistry, biochemistry and biology in his article published in the Dec. 5 issue of Science. The "Perspectives" article reviews what we know about changes in the availability of some key nutrients in the oceans over the sweep of geologic time and suggests future directions for research.

"The history of our planet is like a natural laboratory of 'alternative worlds,'" says Anbar. "The chemical composition of the oceans has changed dramatically over billions of years. Elements that are abundant today were once scarce, and elements that are scarce today were once abundant. So Earth's ancient oceans are a good place to go if we want to understand how organisms and ecosystems evolve to cope with changing abundances of elements. Studying the ancient oceans also stretches our minds to imagine what we might find someday in alien oceans on other worlds."

Visiting billion-year-old oceans is not so easy, however. Anbar explains that biogeochemists cannot directly sample oceans of the past but make inferences about their compositions by examining sedimentary rocks that were deposited on ancient sea floors. For example, the ocean floor rocks from the first half of Earth history include massive deposits of iron oxide - essentially, rust. Those rusty rocks tell us that the oceans in those days were rich in dissolved iron. Today, iron is so scarce in seawater that organisms living in vast areas of the oceans are literally starved for this biologically essential element. These organisms have evolved clever strategies to find and capture this key nutrient.

But Anbar stresses that iron is only one of many critical nutrient elements to consider. Sulfur, nitrogen, phosphorus, copper, zinc, nickel and even obscure elements like molybdenum are all essential nutrients whose abundances have gone up and down in the oceans over geological time. These changes are a consequence of increases in the amount of oxygen in the atmosphere and oceans.

Different elements are important in different ways for biological processes that affect the environment. As a result, Anbar says that changes in ocean chemistry probably had many unusual consequences in Earth history. For instance, he points to a suggestion made by a colleague, Professor Roger Buick of the University of Washington, that changes in the availability of copper could have affected the amount of the gas nitrous oxide - so-called 'laughing gas' - in the atmosphere. The idea follows from the fact that copper is present in the reaction center of the enzyme that bacteria use to convert nitrous oxide to ordinary nitrogen gas. Buick proposes that copper-poor oceans could have led to a 'laughing gas' atmosphere between 1.8 and 0.7 billion years ago. "Ironically, it's no laughing matter," says Anbar. "Nitrous oxide is a powerful greenhouse gas. It may be that copper scarcity helped keep the Earth warm at that time."

Anbar is most excited by the possibility that changes in ocean chemistry affected the makeup of life itself. "Take iron, for example," he contemplates. "It's needed by virtually every organism on the planet. Is that because the basic biochemistry of life on Earth developed in the iron-rich oceans of Earth's distant past? Or is it because the chemical properties of iron are so special that evolution would have selected for it even if it was always rare?"

The answers to such questions will come from continued study of the past combined with research into how the use of elements by organisms is affected by changes in element abundances in their environment. Much of this biological work will take place at ASU in a project Anbar is undertaking with Profs. James Elser and Susanne Neuer in the School of Life Sciences, Everett Shock in the School of Earth and Space Exploration and the Department of Chemistry and Biochemistry, and other ASU scientists. That effort is supported by a new, $7 M grant from the NASA Astrobiology Institute. "NASA is really interested in the idea that they should 'follow the elements' in addition to water when searching for life out there," says Anbar. "They recognize that ASU is an exceptional place for such research."  

"Elements and Evolution" , Ariel D. Anbar, Science 5 December 2008: Vol. 322. no. 5907, pp. 1481 - 1483 DOI: 10.1126/science.1163100

Link to full text

Nov 20, 2008

Rose group develops long lasting moisturizers and sunscreen...

Skin hydration is essential for the proper barrier function of skin. Moisturizers are typically composed of hydrophobic emollients that form an occlusive barrier to prevent water loss through the skin, in combination with hydrophilic humectants that attract and retain water on the skin surface. We have synthesized emollients and humectants that also bear an a,ß-unsaturated thiol ester group, a protein-reactive group that allows covalent bonding to proteins in the outer layer of skin. These compounds are designed to serve as long-lasting moisturizers. The synthesis and reactivity of the moisturizers, as well as a preliminary experiment probing the duration on the skin, are described in the current issue of Bioorganic Chemistry. We found that a fluorescent test compound with skin-binder 1 remained on the skin for 21 days vs. 6 days for the non-reactive control and 12 days for skin-binder 2.

“Emollient, humectant and fluorescent a,ß-unsaturated thiol esters for long-acting skin applications,” Robinson, C., Hartman, R. F. and Rose, S. D., Bioorg. Chem. 2008, 36, 265-270. doi:10.1016/j.bioorg.2008.06.004. (link to abstract)

We also have prepared long-lasting UVA and UVB sunscreens capable of binding to skin. “Kinetics and Mechanism of the Addition of Nucleophiles to a,ß-unsaturated thiol esters,” Hartman, R. F. and Rose, S. D., J. Org. Chem. 2006, 71, 6342-50. doi: 10.1021/jo060191+ (link to abstract)

Nov 5, 2008

There is considerable debate over the existence of non-thermal effects when it comes to explaining the advantages of microwave heating over conventional methods in the field of 'Microwave-Assisted Organic Synthesis'. The Richert group has settled this debate by demonstrating substantial non-thermal effects in a representative polar liquid, propylene carbonate: accelerating the dynamics of the liquid by a factor of two at constant temperature via energy absorption from an external field (as in a microwave oven). The configurational modes (spheres at top of figure) are responsible for this change and do not interact strongly with the virbrational modes that govern temperature. The effects are detected in terms of a modified dielectric relaxation behavior (arrows in low part of figure).

"The Physics of Heating by Time-Dependent Fields: Microwaves and Water Revisited" W. Huang, R. Richert, J. Phys. Chem. B 112 (2008) 9909 - 9913

Abstract: Heating samples by microwave radiation is a particular example of the more general phenomenon where materials absorb energy from an external time dependent field of an electric, magnetic, or mechanical nature. How this compares with conventional heating is a question of continued interest. Here, we show that the origin of the absorptivity determines whether energy accumulates in the slower configurational degrees of freedom or transfers rapidly to the phonon bath, where only the latter situation is equivalent to conventional heating. Based upon time resolved measurements of the configurational temperatures, evidence is provided for simple liquids displaying non-thermal behavior if heated by external fields, with molecules being more mobile than expected on the basis of the actual temperature. However, water and related materials are the exception regarding absorptive heating, because energy is transferred to the phonons more rapidly than it is absorbed from the field and non-thermal effects thus remain absent.

Oct 22, 2008

Greg Holland, Janelle Jenkins and Jeff Yarger have recently published an advanced online article in Chemical Communications entitled:“Quantifying the fraction of glycine and alanine in ß -sheet and helical conformations in spider dragline silk using solid-state NMR"

Silk spun from the major ampullate gland of spiders (dragline silk) has a unique combination of strength and extensibility that renders it one of the toughest materials known. The silk's impressive mechanical properties are related to the primary, secondary and hierarchical structure of the two proteins that comprise the silk: major ampullate spidroin I (MaSp1) and major ampullate spidroin II (MaSp2). It has been recognized for more than a decade that the poly(Ala) that runs in the amino acid sequence of MaSp1 and MaSp2 is primarily in an ordered B-sheet conformation. Double-quantum single-quantum NMR correlation experiments for static samples (DOQSY) showed that glycine is present in a disordered 3₁ helical structure and ß -sheet domains. Recently, it was proposed that alanine and glycine, the two most abundant amino acids in spider silk, are present in both the β -sheet and 3₁-helical regions.

Using through-bond DQ/SQ ¹³C homonuclear correlation NMR experiments the Yarger group has resolved distinct sites for Gly and Ala that represent β sheet and helical structures in plasticized spider silk. These sites can be quantified and correlated with the amino acid sequence of MaSp1 and MaSp2. Since, the ß -sheet domains are thought to provide the spider silk its strength and helical structures its elasticity, an ability to resolve and quantify these two conformations is imperative to understanding the mechanical properties of natural spider silk and guide the production of synthetic silks.

“Quantifying the fraction of glycine and alanine in β -sheet and helical conformations in spider dragline silk using solid-state NMR", Gregory P. Holland, Janelle E. Jenkins, Melinda S. Creager, Randolph V. Lewis and Jeffery L. Yarger, Chemical Communications, 2008, DOI: 10.1039/b812928b

Link to abstract

Oct 9, 2008

Hao Yan and colleagues publish in PNAS on viruses and bacteria acting as factories for nanostructures

Molecular nanostructures - the basic architectural elements of nanotechnology - have been replicated in bacterial cells. The research proves that nature's cellular machinery can be commandeered to mass-produce complex structures and devices for molecular-scale engineering. Together with their colleagues, Hao Yan of Arizona State University in Tempe and Nadrian Seeman of New York University speculate that their method might lead to the merging of nanotechnology and Darwinian natural selection, in which such molecular devices could be created and improved by some artificial evolutionary pressure. The technique, reported in the Proceedings of the National Academy of Sciences, relies on the fact that the nanostructures in question are made from DNA, the genetic material of living cells.

Nature News

Oct 2, 2008

Petra Fromme edits book that presents a comprehensive overview of photosynthetic structures

Petra Fromme is the editor of "Photosynthetic Protein Complexes" (published by Wiley-Blackwell). Professor Fromme gives a comprehensive overview of photosynthesis, quite possibly the most important biological process on earth. This book is essential for anyone involved with photosynthesis and structural biology. The very complex photosynthetic process, apart from its obvious importance, is proving to be key as we strive to replace fossil fuels with renewable resources.

Contributions are made from other members of the Department of Chemistry and Biochemistry viz. Ingo Grotjoham, James Allen, JoAnn Williams and Raimund Fromme. This book should prove very attractive to teachers and researchers not least for its intricate color pictures of protein structures that are freely available to download.

Link to Wiley-VCH

Sep 26, 2008

Herckes group recently publishes with cover in the Annals of Occupational Hygiene

The Herckes group has participated in a study on firefighter exposure to polyaromatic hydrocarbons (PAHs) during prescribed burns. The collaborative effort between the three Arizona Universities (ASU, UA and NAU) investigated PAH concentrations in smoke during prescribed burns in Northern Arizona and monitored PAH metabolites in participating firefighters. The Herckes group contributed the analysis of PAHs in smoke. Results showed that PAH concentrations in fine particulate matter are twice as important during smoldering of the fires than during the ignition stage. While PAH concentrations in inhalable particles were high, the PAH metabolites in the firefighters did not show any significant increase between pre and post exposure. The results of the study have been published in the Annals of Occupational Hygiene (including the cover).

"Occupational PAH Exposures during Prescribed Pile Burns", M. S. Robinson, T. R. Anthony, S. R. Littau, P. Herckes, X. Nelson, G. S. Poplin and J. L. Burgess, Annals of Occupational Hygiene 2008 52(6):497-508; doi:10.1093/annhyg/men027.

Link to abstract

Sep 18, 2008

Ed Skibo's research group has just published (with cover) in Organic & Biomolecular Chemistry

Analogues of the marine natural product Wakayin based on the diimidazo[1,5,4-de, 1,5,4-h]-quinoxaline ring system have been prepared and evaluated with respect to cytostatic and cytotoxic activity. Assays in a 60-cell-line human cancer panel revealed selective activity against cells with the VEGEF (flt-1) receptor.

"Synthesis and in vitro evaluation of imidazole-based wakayin analogues", Hung Hoang, Xiaofen Huang and Edward B. Skibo, Org. Biomol. Chem., 2008, 6, 3059.

Link to abstract

Sep 11, 2008

Single Cell Microfluidics - Alexandra Ros and Tzu-Chiao Chao have published an invited review article in the Journal of the Royal Society Interface

Alexandra Ros and her co-worker Tzu-Chiao Chao summarize important microfluidic developments for intracellular analysis in their invited review article published recently in the Journal of the Royal Society Interface. "Biological analyses traditionally probe cell ensembles in the range of 10³ to 10⁶ cells, thereby completely averaging over relevant individual cell responses, such as differences in cell proliferation, responses to external stimuli or disease onset. In the past years, this fact has been realized and increasing interest has evolved for single cell analytical methods, which could give exciting new insights in genomics, proteomics, transcriptomics and systems biology", says Ros. She further argues that "Microfluidic or lab-on-a-chip devices are the method of choice for single cell analytical tools as they allow for the integration of a variety of necessary process steps involved in single cell analysis, such as selection, navigation, positioning or lysis of single cells as well as separation and detection of cellular analytes. Along with this advantageous integration, microfluidic devices confine single cells in compartments near their intrinsic volume, thus minimizing dilution effects and increasing detection sensitivity." The review gives an overview of the developments and achievements of microfluidic single cell analysis of intracellular compounds in the past few years, from proof of principle devices to applications demonstrating high biological relevance.

"Microfluidic single-cell analysis of intracellular compounds", Tzu-Chiao Chao, Alexandra Ros,Journal of the Royal Society Interface, Issue Volume 5, Supplement 2 / October 06, 2008Pages S139-S150.

Link to abstract  

Sep 3, 2008

David LeBard, Vitaly Kapko, and Dmitry Matyushov have recently published ( cover of the Journal of Physical Chemistry B) a Molecular Dynamics (MD) study on a photosynthetic bacterial reaction center

Biochemistry textbooks describe proteins as hydrophobic environments with little solvation. The recent Molecular Dynamics (MD) simulations of a bacterial reaction center, the most extensive ever done, suggest that this statement applies only to average electrostatic properties. The fluctuations of electrostatic potential at cofactors within the protein matrix are much more intense than previously anticipated. David LeBard, Vitaliy Kapko, and Dmitry Matyushov have found that the breadth of electrostatic fluctuations within the reaction complex are about an order-of-magnitude larger than believed to date. Nevertheless, these results do not contradict the experimental database, and the theory of primary charge separation based on MD input describes recent experiments reported by the Allen and Woodbury groups. These findings were reported in the cover article published in the Journal of Physical Chemistry.

"Energetics and Kinetics of Primary Charge Separation in Bacterial Photosynthesis", David N. LeBard, Vitaliy Kapko, and Dmitry V. Matyushov,. J. Phys. Chem. B, 112 (33), 10322–10342, 2008. 10.1021/jp8016503 Web Release Date: July 18, 2008.

Link to abstract

Aug 25, 2008

Hao Yan and colleagues have recently published in Nature Nanotechnology in the advanced online version

Recent progress in structural DNA nanotechnology has made it possible to organize various molecules such as proteins and nanoparticles while controlling the spacing between them. This has led to the possibility of studying spatially controlled biomolecular interactions. Hao Yan, Yan Liu and co-workers have shown that distance-dependent multivalent ligand-protein binding effects can be systematically investigated by incorporating multiple affinity ligands into DNA nanostructures. They have demonstrated direct visualization of high affinity bivalent ligands being used as pincers to capture and display protein molecules on a nanoarray. These results illustrate the potential of using designer DNA nanoscaffolds to engineer more complex and interactive biomolecular networks.

"Self-assembled DNA nanostructures for distance-dependent multivalent ligand–protein binding", Sherri Rinker, Yonggang Ke, Yan Liu, Rahul Chhabra& Hao Yan, Nature Nanotechnology 3, 418 - 422 (2008)

Link to abstract

May 19, 2008
Michael O'Keeffe and UCLA collaborators - synthesize most complex inorganic material characterized to date

Mike O'Keeffe along with Omar Yaghi's group at UCLA have synthesized and characterized ZIFs (zeolitic imidazolate frameworks) in which metal atoms are linked by functionalized imidazolate rings into zeolite-like tetrahedral frameworks of exceptional porosity and chemical stability and promise for applications in catalysis, gas storage and separations. The Science paper showed how high-throughput methods led to 25 new ZIFs (this should be contrasted to a total of only 175 zeolites known after many decades of intensive research by literally thousands of researchers). The Nature paper (published May 8) described an extraordinary ZIF with colossal cages (composed of over 7000 atoms) that is the most complex inorganic material characterized to date. Both papers showed that ZIFs have exceptional properties in sequestering and purifying CO2 and have great promise for clean energy applications. The materials were synthesized by Yaghi's group and O'Keeffe contributed structural analysis and geometric insights.

"Colossal cages in zeolitic imidazolate frameworks as selective carbon dioxide reservoirs", Bo Wang, Adrien P. Côté, Hiroyasu Furukawa, Michael O'Keeffe& Omar M. Yaghi, Nature 453, 207-211 (8 May 2008) | doi:10.1038/nature06900

Link to abstract

May 12, 2008
ASU researchers synthesize a molecule with self control

Plants have an ambivalent relationship with light. They need it to live, but too much light leads to the increased production of high-energy chemical intermediates that can injure or kill the plant.

The intermediates do this because the efficient conversion of sunlight into chemical energy cannot keep up with sunlight streaming into the plant.

“The intermediates don’t have anywhere to go because the system is jammed up down the line,” says ASU chemist Devens Gust. Plants employ a sophisticated process to defend against damage. To better understand this process, Gust, along with fellow ASU researchers Thomas Moore and Ana Moore, both professors of chemistry and biochemistry, designed a molecule that mimics what happens in nature.

They report results with their molecule in the advanced online publication of Nature Nanotechnology (May 4, 2008).

full story in Press Release

"Self-regulation of photoinduced electron transfer by a molecular nonlinear transducer", Stephen D. Straight, Gerdenis Kodis, Yuichi Terazono, Michael Hambourger, Thomas A. Moore, Ana L. Moore& Devens Gust, Nature Nanotechnology 3, 280 - 283 (2008) Published online: 4 May 2008 | doi:10.1038/nnano.2008.97

Link to abstract

April 30, 2008
International team of researchers explain how birds navigate

Upon excitation with light, an electron moves from one end of the molecule to the other. The time it takes for this electron to return to its initial position is sensitive to the magnitude and direction of magnetic fields similar to those of the Earth. Birds may use a similar phenomenon to navigate.

It has long been known that birds and many other animals including turtles, salamanders and lobsters, use the Earth’s magnetic field to navigate, but the nature of their global positioning systems (GPS) has not been completely understood.

One school of thought hypothesizes that birds use magnetically-sensitive chemical reactions initiated by light (called chemical magnetoreception) to orient themselves, but no chemical reaction in the laboratory, until now, has been shown to respond to magnetic fields as weak as the Earth’s.

Scientists from Arizona State University and the University of Oxford, whose work appears in the April 30 advanced online publication of the journal Nature, have synthesized and studied a sophisticated molecule that, under illumination, is sensitive to both the magnitude and the direction of magnetic fields as tiny as the Earth’s, which is, on average, one-twenty thousandth as strong as a refrigerator magnet.

ASU’s Devens Gust, professor of chemistry and biochemistry in the College of Liberal Arts and Sciences, states that “although the chemical magnetoreception mechanism for avian magnetic navigation has been discussed by many investigators, our research provides the first proof that this mechanism can actually function with magnetic fields as small as those of the Earth.”

"Chemical compass model of avian magnetoreception", Kiminori Maeda, Kevin B. Henbest, Filippo Cintolesi, Ilya Kuprov, Christopher T. Rodgers, Paul A. Liddell, Devens Gust, Christiane R. Timmel& P. J. Hore, Nature (30 Apr 2008), doi: 10.1038/nature06834.

Link to abstract

Full story from ASU News

April 25, 2008
Fromme and Thorpe Groups Develop new technique for fitting cryo EM Maps of Proteins

Recent experimental advances in producing density maps from cryo-electron microscopy (cryo-EM) have challenged theorists to develop improved techniques to provide structural models that are consistent with the data and that preserve all the local stereochemistry associated with the biomolecule. The Fromme and Thorpe groups have developed a new technique that maintains the local geometry and chemistry at each stage of the fitting procedure. They show that by incorporating the correct local stereochemistry in the modeling, structures can be obtained with effective resolution that is significantly higher than might be expected from nominal cryo-EM resolution.

Their research was depicted on a recent cover of the Biophysical Journal: " Fitting Low-Resolution Cryo-EM Maps of Proteins Using Constrained Geometric Simulations ", Craig C. Jolley, Stephen A. Wells, Petra Fromme, and M. F. Thorpe Biophysical Journal, 94, 2008, pp 1613–1621

Link to abstract , Link to Cover Story

April 18, 2008
David LeBard and Dmitry Matyushov find Gigantic Reorganization Energy of Electron Transfer for a Hydrated Metalloprotein

When people think about about the transport of electrons in biological energy chains they turn their attention to redox potentials and Gibbs energies to find energetically downhill pathways. In order to access the activation energy, one also needs an additional energy called the reorganization energy of the hydrating water and the protein. Two novel characteristics of the problem came from recent extensive Molecular Dynamics simulations of the photosynthetic redox protein plastocyanin. First, it was found that the breadth of electrostatic fluctuations created by hydrating water far exceeds all previous estimates and results in a gigantic reorganization energy. Second, it was found that the spectrum of relaxation times is so wide that most biological electron transitions find themselves in non-ergodic regime when some parts of the fluctuation spectrum are dynamically frozen. This finding suggests a possibility that nature plays with both the Gibbs energies and relaxation time-scales in optimizing its energy chains.

The results were reported in the recent issue of the J. Phys. Chem. B

"Glassy Protein Dynamics and Gigantic Solvent Reorganization Energy of Plastocyanin", David N. LeBard and Dmitry V. Matyushov, J. Phys. Chem. B, 112 (16), 5218 -5227, 2008. 10.1021/jp709586e S1520-6106(70)09586-X

Link to abstract , Link to full text

April 14, 2008
Richert group turns the table on liquid studies

When we use a mercury thermometer to monitor a baby's fever we are taking advantage of the way temperature changes the liquid's density. We flow heat into the liquid by collisions with the molecules of a hotter body, and the liquid responds by changing its "molecular configuration" to one with lower density.

Most measurements of temperature effects on materials are made this way... But not all. Ranko Richert's research group has found a way to change the configuration first. It is likely that this is the way the ARMY's recently developed "active denial" non-lethal defence system also works.

"It is a new way of thinking about liquids," adds Regents' Professor Austen Angell. " I think people will take a lot of notice of this development." Richert's results were reported in the physic's community's top journal Physical Review Letters.

"Measuring the Configurational Heat Capacity of Liquids", L.-M. Wang, R. Richert, Phys. Rev. Lett. 99, 185701 (2007).
Abstract: A high electric field impedance experiment on supercooled molecular liquids is employed to transfer energy to the slow modes by absorption from the field and detect the increase of their 'configurational temperature', Tcfg, via the change of the relaxation times. This allows us to determine the configurational heat capacity, which accounts for most of the excess heat capacity for stronger liquids, but for only half of the heat capacity step in the case of more fragile systems. It is also observed that Tcfg gradually approaches the phonon temperature on the structural relaxation time scale.

Link to abstact

April 7, 2008
Mark Hayes and colleagues are making progress with their small scale proteomics research

One of the major challenges in developing personalized medicine is analyzing the stunningly complex mixture of biomolecules in typical human fluid samples-some estimate as much as a million different chemical species. The revolution in micro and nanoscale fabrication and understanding has begun to allow new strategies to be developed. One shown here uses a micro and nanoscaled surface (designed after the self-cleaning 'Lotus Leave') combined with a separations technique to divide proteins within a single droplet for further processing. The use of 'digital magnetofluidics' and 'within-droplet separations' are both unique capabilities and the combination of them provides a powerful new tool to analyze complex biological mixtures more effectively.

The work is centered in Tony Garcia's lab at Harrington Department of Bioengineering, Arizona State University with the collaboration between Ana Egatz*, Antonio A. Garcia*&**, Mark Hayes**, Sonia Melle***, Miguel Angle Rubio****, Nicole Zwick**, Melissa Mclauchlin**, and Manuel Marquez*.

*Harrington Department of Bioengineering, Arizona State University, ** Department of Chemistry and Biochemistry, Arizona State university, ***Universidad Complutense de Madrid, ****Universidad Nacional de Educacion a Distancia.

April 1, 2008
Discovery of Quinolinediones Exhibiting a Heat Shock Response and Angiogenesis Inhibition

A series of substituted quinoline-5, 8-diones were synthesized and evaluated as inhibitors of the chaperone protein Hsp90 using two assays: competition for binding to C-terminal ATP-binding site and competition for binding to N-terminal ATP-binding site. In addition, the ability of the compounds to induce the heat shock response was determined using a reporter fibroblast cell line. Of all the compounds assayed, only 6-aziridinyl-2-biphenylquinoline-5, 8-dione induced a heat shock response and did so without interacting at the ATP binding sites of Hsp90. COMPARE analysis was carried out on quinoline-5, 8-diones active in the National Cancer Institute's 60-cell line screen with the goal of discovering quinoline-5, 8-dione structures that interact with other cellular targets (molecular targets) important for cancer chemotherapy. COMPARE analysis led to the discovery of a combretastatin-like quinoline-5, 8-dione structure that in fact inhibited angiogenesis.

"Discovery of Quinolinediones Exhibiting a Heat Shock Response and Angiogenesis Inhibition ", Robert H. J. Hargreaves, Cynthia L. David, Luke J. Whitesell,§ Daniel V. LaBarbera,† Akmal Jamil, Jean C. Chapuis, and Edward B. Skibo, J. Med. Chem., ASAP Article, 10.1021/jm7014099

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March 26, 2008
International team of scientists discover clue to delay of life on Earth

Scientists from around the world have reconstructed changes in Earth’s ancient ocean chemistry during a broad sweep of geological time, from about 2.5 to 0.5 billion years ago years ago. They have discovered that a deficiency of oxygen and the heavy metal molybdenum in the ancient deep ocean may have delayed the evolution of animal life on Earth for nearly 2 billion years. full story

"Tracing the stepwise oxygenation of the Proterozoic ocean", C. Scott, T. W. Lyons, A. Bekker, Y. Shen, S. W. Poulton, X. Chu & A. D. Anbar, Nature 452, 456-459 (27 March 2008) | doi:10.1038/nature06811

Link to abstract

March 25, 2008
Dielectrophoretic manipulation of DNA: Separation and polarizability

New faculty member Alexandra Ros and coworkers from Bielefeld University (Germany) have demonstrated the first example of DNA separation based on dielectrophoresis. Although the separation of polymers based on the combination of dielectrophoretic trapping and electrophoretic forces was proposed 15 years ago, the experimental realization had not been reported.

They addressed this problem for long DNA fragments in a simple and easy-to-fabricate microfluidic device in which the DNA is manipulated by electrophoresis and by electrodeless dielectrophoresis. By slowly increasing the strength of the dielectrophoretic traps in the course of the separation experiments, they were able to perform efficient and fast DNA separation according to length for two different DNA conformations: linear and supercoiled covalently closed circular (ccc) plasmid DNA. The underlying migration mechanism - a thermally induced escape process out of the dielectrophoretic traps in the direction of the electrophoretic force - is sensitive to different DNA fragments due to the length-dependent DNA polarizability. The migration mechanism is also exploited for the quantitative measurement of the DNA polarizability. This new and simple technique opens way to a systematic characterization of the polarizability not only for DNA with respect to its length-dependence, but also for other biomolecules, such as proteins, and also with respect to other molecular properties, such as conformation. These results have further direct implications to future biotechnological applications like gene therapy and DNA vaccination.

"Dielectrophoretic manipulation of DNA: Separation and polarizability", J. Regtmeier, T. T. Duong, R. Eichhorn, D. Anselmetti, A. Ros, , Analytical Chemistry, 79, 3925-3932, (2007).

Link to abstract

March 20, 2008
The March issue of Journal of Natural Products is a special issue in Honor of Professor G.Robert Pettit

Gordon M. Cragg, Guest Editor, Richard G. Powell, Associate Editor, and Sheo B. Singh, Guest Editor: It is an honor and a pleasure for us to serve as Guest Editors of this issue of the Journal of Natural Products dedicated to Professor George Robert (Bob) Pettit. We wish to express our sincere thanks to Bob’s former students, postdoctoral fellows, visiting scientists, and his many colleagues from the former Cancer Research Institute at Arizona State University and institutions worldwide, for submitting such a diverse set of excellent manuscripts for this issue. Their generosity in terms of time and effort is greatly appreciated and provides well-deserved recognition of the many outstanding contributions that Bob has made to the field of natural products science and anticancer drug discovery over the past five decades.

Bob Pettit was born on June 8, 1929, in Long Branch, New Jersey. He gained his B.S. in chemistry at Washington State University in 1952 and proceeded to Wayne State University, where he completed his M.S. in heterocyclic chemistry in 1954 and his Ph.D. in steroid chemistry in 1956, both under the direction of Professor Carl Djerassi. Bob remembers the Djerassi group of the mid-1950s as an exciting and diverse group of talented young scientists from many parts of the world, including Australia, India, Israel, New Zealand, and the United Kingdom, who proceeded to prominent positions in academia, government, and industry. These included Albert Bowers and John Zderic, who later became CEO and Vice President of Syntex, respectively. In 1956, Bob moved to Norwich Eaton Pharmaceuticals (now Proctor and Gamble) as Senior Research Chemist, and in 1957 he transferred to the University of Maine as Assistant Professor, rising through the ranks to become Full Professor in 1965. After a period as Visiting Professor at Stanford University, he accepted a full Professorship in the Chemistry Department at Arizona State University in late 1965. From 1974 to 1975 he served as Director of the Cancer Research Laboratory, and in 1975 he became the Director of the newly established Cancer Research Institute. Since 1986 he has also occupied the position of Dalton Professor of Cancer Research and Medicinal Chemistry. full story from the Journal of Natural Products.

"Special Issue in Honor of Professor George Robert Pettit",Gordon M. Cragg, Guest Editor, Richard G. Powell, Associate Editor, and Sheo B. Singh, Guest Editor, J. Nat. Prod., 71 (3), 297–299, 2008. 10.1021/np700714j

March 3, 2008
Meteorite molecules mirror those on Earth  

Courtesy of Linda Welzenbach, Smithsonian Institution, and the Antarctic Search for Meteorites Program

An important discovery has been made with respect to the mystery of “handedness” in biomolecules. Researchers led by Sandra Pizzarello, a research professor at Arizona State University, found that some of the possible abiotic precursors to the origin of life on Earth have been shown to carry “handedness” in a larger number than previously thought.

The work is being published in this week’s Proceedings of the National Academy of Sciences (PNAS). The paper is titled, “Molecular asymmetry in extraterrestrial chemistry: Insights from a pristine meteorite,” and is co-authored by Pizzarello and Yongsong Huang and Marcelo Alexandre, of Brown University.

Pizzarello, in ASU’s Department of Chemistry and Biochemistry, worked with Huang and Alexandre in studying the organic materials of a special group of meteorites that contain among a variety of compounds, amino acids that have identical counterparts in terrestrial biomolecules. These meteorites are fragments of asteroids that are about the same age as the solar system (roughly 4.5 billion years.) Scientists have long known that most compounds in living things exist in mirror-image forms. The two forms are like hands; one is a mirror reflection of the other. They are different, cannot be superimposed, yet identical in their parts. full story...

Link to abstract

Jan 29, 2008
Herckes group develops new methods for atmospheric detection of Hydrocarbons

The Herckes group in collaboration with researchers at the University of Strasbourg have developed new methods to determine oxygenated (oxy-PAH) and nitrated polyaromatic hydrocarbons (nitro-PAH) in the atmosphere. These pollutants can be emitted directly into the atmosphere through combustion processes or formed in situ through photo oxidation. They are of particular interest due to their high toxicity and carcinogenicity. The manuscripts describe new methods using liquid chromatography with online derivatisation and fluorescence detection respectively liquid chromatography with tandem mass spectrometry to detect and quantify these species. These techniques will be instrumental for atmospheric occurrence studies. The manuscripts also report first ambient data on these species in atmospheric particulate matter in Tempe (AZ) and Strasbourg (France).

"Determination of oxygenated polycyclic aromatic hydrocarbons in atmospheric aerosol samples by liquid chromatography–tandem mass spectrometry ", O. Delhomme, M. Millet, P. Herckes, Talanta, 74, 703-710, 2008.

Link to abstract

"Post-column derivatisation of nitro-polycyclic aromatic hydrocarbons for their analysis by HPLC fluorescence. Application to atmospheric aerosols", O. Delhomme, P. Herckes, M. Millet, Analytical and Bioanalytical Chemistry, 389, 1953-1959, 2007.

Link to abstract

Jan. 10, 2008
Nanotechnology innovation may revolutionize gene detection in a single cell

Hao Yan and his research group have developed the world’s first gene detection platform made up entirely from self-assembled DNA nanostructures. The results, appearing in the January 11 issue of the journal Science, could have broad implications for gene chip technology and may also revolutionize the way in which gene expression is analyzed in a single cell.

"Self-Assembled Water-Soluble Nucleic Acid Probe Tiles for Label-Free RNA Hybridization Assays", Yonggang Ke, Stuart Lindsay, Yung Chang, Yan Liu,, Hao Yan. Science 11 January 2008: Vol. 319. no. 5860, pp. 180 - 183.

Link to abstact

Dec. 12, 2007
In Vitro Selection of Histone H4 Aptamers for Recognition Imaging Microscopy

In a recent issue of the Journal of the American Chemical Society, Chaput and Lindsay report the in vitro selection and evaluation of histone H4 aptamers as affinity reagents in the atomic force microscopy technique known as recognition imaging microscopy. In contrast to commercial antibodies, the selected aptamers showed high binding affinity and selectivity, both in solution and on the cantilever tip of an atomic force microscopy. Their strategy now opens up the possibility that aptamers could be used as antibody surrogates in studying key epigenetic modification involved in chromatin remodeling.

“In Vitro Selection of Histone H4 Aptamers for Recognition Imaging Microscopy”, Liyun Lin, Doris Hom, Stuart M. Lindsay, and John C. Chaput. J. Am. Chem. Soc. 129(2007), 14568-14569.

Link to abstract

Nov. 30, 2007
Permanent Electric DipoleMoment of Molybdenum Carbide

Understanding the nature of the transition metal/carbon bond is fundamental to many areas of organometallic chemistry and catalysis. The permanent electric dipole moment, μ_e, is the best gauge of the polarity of a chemical bond and a comparison of theoretical and experimentally derived values of μ_e is a primary means of assessing the quality of electronic structure calculation being developed to model properties of transition metal containing molecules. The need for this benchmark data on simple metal containing molecules has increased as electronic structure computational approaches have evolved from traditional high level ab initio methods to the current extensively implemented density functional theory (DFT) methods because the results of DFT predictions depend radically on the nature of both the functional and basis set employed. The Steimle lab has recently succeeded in experimentally determining μ_e of molybdenum monocarbide, MoC, and thus the polarity of this important metal carbide chemical bond. The experiment, which is unique to the ASU group, employs ultra-high resolution optical Stark spectroscopy of molecular beam samples. A manuscript describing the results was recently accepted for publication in the Journal of Chemical Physics.

“Permanent Electric DipoleMoment of Molybdenum Carbide”, H. Wang, W.L. Virgo, J. Ven, and T. C. Steimle, J. Chem. Physics Vol 127, 124302 (2007).

Link to abstract

Nov. 15, 2007
Synthetic hydrogenases: Incorporation of an iron carbonyl thiolate into a designed peptide

Hydrogen is one of the leading contenders for fuel of the future, and cheap, renewable catalysts for its production are highly sought after. Although typical industrial catalysts utilize precious metals such as platinum, hydrogenases, the biological catalysts for the reversible oxidation of hydrogen, utilize the base metal iron. However, unraveling the fundamental mechanism of the catalysis of biological hydrogen production has not proven easy. Classically, two approaches have been taken: study of the intact enzymes and synthesis of small inorganic model systems. While significant progress has been made, both methods have left many questions unanswered and a need for new tactics exists.

In a recent publication, Jones and coworkers are offering a new alternative. They have constructed the first intermediate sized model system incorporating features of both the inorganic active site and the protein scaffold. The synthesis and characterization of a de novo designed peptide incorporating an iron carbonyl thioloate mimic of the [FeFe]-hydrogenase active site, the first generation of peptide-based, artificial hydrogenases, are described. This peptide and the reaction with cysteine used for creation of the metallocluster within it open the door for future generations of artificial hydrogenases. These artificial proteins will prove to be invaluable tools for testing hypotheses regarding hydrogenase biosynthesis and mechanism as well as platforms for design of novel, artificial redox catalysts.

"Synthetic hydrogenases: Incorporation of an iron carbonyl thiolate into a designed peptide", A. K. Jones, B. R. Lichtenstein, A. Dutta, G. Gordon, and P. L. Dutton, J. Am. Chem. Soc., 129 (2007).

Link to abstact

Nov. 7, 2007
Enzyme activity at the flick of a switch

Joseph Wang and co-workers have used a combination of nanowires and nanotubes to create a switchable bioelectronic device for the on-demand transformation of alcohols to aldehydes.

Wang's system uses nickel-gold nanowires, which have an enzyme trapped halfway along them, in combination with an electrode coated with carbon nanotubes. The orientation of the nanowires in the device can be switched from vertical to horizontal by a magnetic field.

In the horizontal position, contact between the enzyme and the electrode allows the enzyme - in this case alcohol dehydrogenase (ADH) - to catalyse the transformation of ethanol to acetaldehyde. Regeneration of the enzyme's cofactor (NAD⁺) by the nanotube surface maintains the catalytic activity, and allows analysis by electrochemical methods. This means the device could be used as an alcohol sensor.

When the nanowires are switched to the vertical position, the reaction is inhibited because the enzyme has no contact with the electrode.  Wang says this switchability could hold great promise for regulating the operation of biofuel cells or bioreactors.

Frederic Barriere, an expert in bioelectrochemistry at the University of Rennes, France, sees of the advantages of Wang's system over established methods. 'The oxidation of NADH on traditional electrodes quickly fails because of adsorption and surface fouling. The use of electrodes coated with acid-purified carbon nanotubes avoids this problem,' said Barriere.

"Adaptive nanowire–nanotube bioelectronic system for on-demand bioelectrocatalytic transformations", Rawiwan Laocharoensuk, Andrea Bulbarello, Saverio Mannino and Joseph Wang, Chem. Commun., 2007, 3362 - 3364, DOI: 10.1039/b708313k

Link to abstract

Oct. 31, 2007
Ranko Richert's article featured on the ACS Publications web as a "Hot Paper"
Solvation Dynamics and Electric Field Relaxation in an Imidazolium-PF₆ Ionic Liquid: from Room Temperature to the Glass Transition

Time-resolved phosphorescence spectra and anisotropy of quinoxaline were measured in an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM-HFP), in its supercooled state near the glass-transition temperature. The solvation dynamics results are compared with the rotational motion of the probe and with the dielectric behavior of the neat ionic liquid. The dynamics in the viscous state are highly dispersive and show a super-Arrhenius temperature dependence, as typical for glass-forming materials. Combined with room-temperature results, solvation dynamics is observed to follow the structural relaxation times in terms of /T for more than 10 decades, from subnanoseconds at room temperature to seconds near the glass-transition temperature Tg. The dielectric modulus relaxation follows this trend only for temperatures T > 1.2Tg and departs significantly from /T in the 1.1Tg > T > Tg range. This deviation is reminiscent of the enhanced translational diffusion or fractional Stokes-Einstein behavior observed in many fragile supercooled liquids. Because the electric field relaxation in BMIM-HFP includes dc conductivity, this correlation function involves translational motion and thus displays the effect of enhanced diffusivity. A microscopic model is required for rationalizing the decoupling of solvation dynamics from the longitudinal time scales and the limitation of this effect to the viscous regime with T < 1.2Tg.

"Solvation Dynamics and Electric Field Relaxation in an Imidazolium-PF₆ Ionic Liquid: from Room Temperature to the Glass Transition", Naoki Ito and Ranko Richert, J. Phys. Chem. B, 111 (18), 5016 -5022, 2007.

Link to abstract

Oct. 23, 2007
Metal Turned to Glass

In order to form a glass by cooling a liquid, the normal process of solid crystallization must be bypassed. Achieving that for a pure metal had seemed impossible — until pressure was applied to liquid germanium. In Yarger , Angell and their research team's new paper published in Nature, another member has been added to the ubiquitous family of materials: a glass made by cooling a pure, ‘monatomic’ metal.

"Vitrification of a Monatomic Metallic Liquid", M. H. Bhat, V. Molinero, E. Soignard, V. C. Solomon, S. Sastry, J. L. Yarger& C. A. Angell, Nature 448, 787-790 (2007).

Link to abstract

Oct. 16, 2007
Experimental Evidence That GNA and TNA Were Not Sequential Polymers in the Prebiotic Evolution of RNA

In this month’s issue of the Journal of Molecular Evolution, Chaput and coworkers demonstrate that glycerol nucleic acid (GNA) and threose nucleic acid (TNA) were not consecutive biopolymers in the same evolutionary pathway that gave rise to RNA in a hypothetical RNA world. Coupled with their chemical simplicity, polymers for both systems are known to form stable Watson-Crick duplex structures with themselves and RNA, thereby providing a possible mechanism for the transfer of genetic information between successive genetic systems. Using chemical synthesis and molecular biology, the Chaput lab demonstrated that complementary GNA and TNA polymers are unable, even after prolonged incubation times, to adopt stable helical structures by intersystem cross-pairing. This experimental observation suggests that GNA and TNA, whose structures derive from one another, were not consecutive polymers in the same evolutionary pathway to RNA—a result that provides new constraints on models that describe the evolution of early genetic systems.

"Experimental Evidence That GNA and TNA Were Not Sequential Polymers in the Prebiotic Evolution of RNA", Ying-Wei Yang, Su Zhang, Elizabeth O. McCullum, and John C. Chaput. J. Mol. Evol. 2007, 65, 289–295.  

Link to abstract

Oct. 9, 2007

Anbar and members of his group are involved in two new studies that provide evidence of the presence of O₂ in the atmosphere tens of millions years before the Great Oxidation Event. This event, which began around 2.4 billion years ago, marked the Earth’s irreversible transition to an oxygenated world that can support complex life. The detailed cause of this event is unknown. The two studies were published in the Sept. 28 issue of Science.

The researchers analyzed samples of 2.5 billion year old seafloor obtained for the study by subsurface drilling in Western Australia. A team led by Anbar examined the amounts of the trace metals molybdenum, rhenium and uranium using ICP mass spectrometry (more). The presence of these elements in oceans and ocean sediments depends on the oxidation state of the environment. Another group, led by Alan J. Kaufman at the University of Maryland, focused on sulfur isotope variations that are also sensitive to O₂abundance (more). Both groups found unexpected, correlated changes that suggest the presence of small but significant amounts of O₂ in the environment 2.5 billion years ago, and a shift from lower O₂ abundance prior to that time. These two lines of evidence strengthen the notion that organisms began producing O₂ long before the Great Oxidation Event, and hence that the rise of O₂ in the atmosphere was ultimately controlled by geological processes that prevented biologically-produced O₂ from accumulating in the atmosphere before that time.

This research was supported by major grants from NASA and the National Science Foundation.

Link to abstracts:
http://www.sciencemag.org/cgi/content/abstract/317/5846/1900?etoc,
http://www.sciencemag.org/cgi/content/abstract/317/5846/1903?etoc

Oct. 2, 2007
LDA “double-counting” energy expression

The LDA+U method has been around for about two decades, as the most popular way in investigation of strongly-correlated electron systems such as high-Tc superconductors, colossal magneoresistance oxides and heavy fermions. By critically examining the LDA+U method regarding its self-interaction correction of the LDA, the Seo group has derived an LDA “double-counting” energy expression which led to a more reasonable self-interaction correction in an alternative LDA+U scheme (Self-interaction correction in the LDA+U method, PHYSICAL REVIEW B 76, 033102, 2007). The new method is based on the previous work of the Seo group that resulted in a unified theory of magnetic exchange interactions in various magnetic materials (Density functional perturbational orbital theory of spin polarization in electronic systems. I. Formalism, THE JOURNAL OF CHEMICAL PHYSICS 125, 154105, 2006). It is anticipated that the new method correctly predicts the magnetic ground states of the strongly-correlated electron systems in first principle electronic band structure calculations and is currently implemented by physicists in Leibniz Institute for Solid State and Materials Research in Dresden, Germany.

Link to abstract

Sep. 24, 2007
Fluorescence Properties and Photophysics of the Sulfoindocyanine Cy3 Linked Covalently to DNA

The Levitus lab has undertaken an extensive study of the photophysical and fluorescence properties of Cy3, one of the most popular fluorescent dyes used in biophysical and biological applications. In particular, the team concentrated on elucidating how these properties depend on the local environment of the dye when it is attached to DNA. The authors demonstrated that specific interactions between the dye and DNA are responsible for dramatic changes in its fluorescence efficiency (‘brightness’). These interactions also affect the local mobility of the probe, complicating the analysis of experiments where Cy3 is used as the donor in a FRET pair. The remarkable variations in the photophysical properties of Cy3-DNA constructs demonstrate that caution should be used when Cy3 is used in studies employing DNA conjugates. This is particularly critical when this dye is used to probe conformational dynamics in nucleic acids or DNA-protein interactions. This work was recently published in J. Phys. Chem. B, the most cited journal in Physical Chemistry.

"Fluorescence Properties and Photophysics of the Sulfoindocyanine Cy3 Linked Covalently to DNA" Matthew E. Sanborn, Brian K. Connolly, Kaushik Gurunathan, and Marcia Levitus. J. Phys. Chem. B, 111 (37), 11064 -11074, 2007 

Link to abstract

Sep. 18, 2007
Spatially Addressable Multiprotein Nanoarrays Templated by Aptamer-Tagged DNA Nanoarchitectures

The Yan lab has constructed, using a self-assembly approach, arrays of multiple proteins onto rigid DNA nano-scaffolds. In this work, self-assembled DNA tiles were designed to bear protein-binding nucleic acid loops, known as aptamers, at defined positions. The authors demonstrated that proteins can be organized into well-defined geometric patterns with accurate control of the protein placement at nanometer scale. Such protein nanoarrays could be used to investigate distance dependent biomolecular interactions, with applications in medical diagnostics. This work was recently published in J. Am. Chem. Soc. [ Chhabra, R.; Sharma, J.; Ke, Y.; Liu, Y.; Rinker, S.; Lindsay, S.; Yan, H., Spatially Addressable Multiprotein Nanoarrays Templated by Aptamer-Tagged DNA Nanoarchitectures. J. Am. Chem. Soc.129, 10304-10305 ( 2007 )] and highlighted in Nature Nanotechnology. http://www.nature.com/nnano/reshigh/2007/0807/full/nnano.2007.287.html

Link to abstract

Sep. 12, 2007
Mutations in telomerase genes linked to hereditary lung disease

The Chen lab together with researchers at Johns Hopkins University have discovered an important genetic link in a hereditary form of a fatal lung disease, idiopathic pulmonary fibrosis (IPF) which affects more than 50,000 Americans annually.

The ends of human chromosomes are normally capped by special DNA-protein complexes, called telomeres, that consist of repetitive DNA and associated proteins. Telomerase is the key enzyme that maintains the integrity of the telomere caps. In this study, mutations in two of the telomerase genes, telomerase reverse transcriptase (TERT) and telomerase RNA (TR), were found in six families that suffered from inherited IPF. Further analyses showed that these telomerase gene mutations resulted in a reduction of telomerase enzyme activity and shortening of telomere length, which has been shown to cause cell death. This finding provides a target for genetic testing and hopefully gene therapy in the future.

The work is published in the March 29, 2007 issue of the New England Journal of Medicine, the #1 journal in medicine with an impact factor of 51.296.

“Telomerase mutations in families with idiopathic pulmonary fibrosis,” M. Armanios, J.L. Chen, W.E. Lawson, J.K. Alder, R.G. Ingersoll, C. Markin, M. Xie, J. Cogan, J.A. Philips III, P.M. Lansdorp, C.W. Greider and J.E. Loyd, New England Journal of Medicine 356 1317-1326 (2007).

Link to abstract

Sep. 4, 2007
X-ray Structure of Cerulean GFP: A Tryptophan-Based Chromophore Useful for Fluorescence Lifetime Imaging

Wachter and coworkers have recently discovered a pH-dependent conformational switch with optical read-out in an engineered cyan fluorescent protein that bears an indole-based fluorophore. The observed optical modulation may be related to photo-switching events that involve cis-trans isomerization of the spontaneously formed intrinsic chromophore.

Cyan fluorescent proteins belong to a group of proteins that are genetically encodable fluorescent markers widely used for in vivo labeling applications in biomedical research. In the present work, Wachter and co-workers provide a structural rational for the enhanced fluorescence properties of Cerulean GFP, a cyan fluorescent protein that was rationally engineered to be useful in non-invasive live tissue imaging techniques such as FRET (Förster resonance energy transfer) and FLIM (fluorescence lifetime imaging).

This work is published as an ACCELERATED PUBLICATION in the September 4 issue of the journal Biochemistry Volume 46, and will be featured as a "2007 HOT ARTICLE" by the journal, see link below. http://pubs3.acs.org/acs/journals/hot_article.menu?in_coden=bichaw

"X-ray Structure of Cerulean GFP: A Tryptophan-Based Chromophore Useful for Fluorescence Lifetime Imaging," Malo, G. D., Pouwels, L. J., Wang, M., Weichsel, A., Montfort, W. R., Rizzo, M. A., Piston, D. W., Wachter, R. M., Biochemistry (Accelerated Publication) 46 9865-9873 (2007).

Link to abstract

Aug. 27, 2007
Sweet entanglement: multivalent binding to sugar-coated gp120 is crucial for the anti-HIV activity of cyanovirin

The ability of attaching sugars to proteins, called glycosylation, is typical of eukaryotic cells. However, HIV and related viruses are able to hijack the host’s cellular enzymes to glycosylate their own surface proteins in an attempt to escape the host’s immune response to infection and facilitate viral transmission. The amino acid composition of a protein influences the type, level and pattern of glycosylation. Thus, the molecular signature of the glycans attached to the HIV envelope protein gp120 is unique and distinct from endogenous proteins, and constitutes an attractive target for novel antiviral compounds.

The Ghirlanda lab has recently discovered the molecular mechanism of action of a potent anti-HIV protein, cyanovirin, paving the way for the design of improved antiviral proteins. The findings are presented in a paper published on Biochemistry this month. In cyanovirin, the anti-HIV activity mediated by its high-affinity binding to oligosaccharides on the viral surface envelope protein gp120. The protein contains two carbohydrate-binding domains, A and B, each of which can bind short oligomannosides in vitro.

Until now, it was not clear whether the interaction with gp120 involved a single domain, or both domains simultaneously. The model could be further complicated complicated by the formation of a domain-swapped dimer form, in which part of each domain is exchanged between two monomers, which contains four functional carbohydrate-binding domains.

To clarify whether multivalent interactions with gp120 are necessary for the antiviral activity the group engineered a novel mutant, P51G-m4-CVN, in which the binding site on domain A has been knocked out; in addition, a P51G mutation prevents the formation of domain-swapped dimers under physiological conditions. The crystal structures at 1.8 Å of the free and of the dimannose-bound forms of P51G-m4-CVN, solved in collaboration with the Fromme group, reveals a monomeric structure in which only domain B is bound to dimannose. P51G-m4-CVN binds gp120 with affinity almost two orders of magnitude lower than wt-CV-N, and is completely inactive against HIV. The tight binding to gp120 is recovered in the domain-swapped version of P51G-m4-CVN, prepared under extreme conditions.

These findings demonstrate that the presence of at least two oligomannoside binding sites, either by the presence of intact domains A and B or by formation of domain-swapped dimers, is essential for activity.

Dr. Ghirlanda is designing novel antiviral agents based on the concept of multivalent interactions, by optimizing the oligomannose binding site to further improve its affinity, and by reengineering the protein to better control its oligomerization state.

"A Monovalent Mutant of Cyanovirin-N Provides Insight Into the Role of Multiple Interactions with gp120 for Antiviral Activity," R. Fromme, Z. Katiliene, F. Bogani, B. Giomarelli, T.Mori, J. McMahon, P. Fromme and G.Ghirlanda, Biochemistry 46 9199-9207 (2007).

Link to abstract