Chemistry & Biochemistry News

MasterCard Foundation scholar Vera Nyarige is studying to become an oncologist.

Vera Nyarige, a biochemistry major, is looking forward to networking with other students from African nations who are convening at Arizona State University for the first time to share experiences and participate in team-building exercises with MasterCard Foundation Scholars from universities across the globe.

“I’m looking forward to meeting other scholars, socializing and learning ideas to give back to their countries and understand how they want to make Africa a better place and how we can work together to achieve that,” Nyarige said.

Scholars will brainstorm ways to build a strong network among their peer scholars, learn about internship opportunities in Africa and develop initial networking tools during the events this weekend.

“We are very excited to host the first Global Scholars Convening with participants from 15 partners of The MasterCard Foundation Scholars Program," said Meggan Madden, director of The MasterCard Foundation Scholars Program at ASU. "Our ASU scholars will serve as delegates and facilitators at the convening, giving them a unique opportunity to cultivate their leadership and communication skills.”

Ten students from seven African nations started their first year at Arizona State University as MasterCard Foundation Scholars during the fall of 2012. Since arriving, they have excelled in their studies and have become valued members of the university community.

The MasterCard Foundation Scholars Program is a $500 million education initiative that identifies academically talented young people from economically disadvantaged communities in developing countries – particularly from Africa. The program provides them with access to quality secondary and university education, and prepares them with the values, knowledge, skills and leadership needed to fuel economic and social progress across Africa. Over the next 10 years, an estimated 15,000 young people will be selected into The MasterCard Foundation Scholars Program. The program currently has 145 scholars at the university level, and 600 scholars at the secondary school level.

Nyarige plans to become an oncologist to fight cancer in Kenya where cancer cases often turn fatal and there are not enough oncologists to treat patients, she said.

“I am on my way to realizing my dream because of The MasterCard Foundation,” Nyarige said. “Many cases of cancer were being reported in Kenya and in most cases they led to death. My best friend lost her parents to cancer. … At least 50 patients die of cancer daily in Kenya.”

Through a network of education institutions and non-profit organizations, the program provides holistic support to deserving young people who have leadership potential, and are committed to improving the lives of others in their home communities. Students enrolled in the Scholars Program receive comprehensive scholarships, mentoring, leadership development and life skills support as they transition from secondary to university education and into the workforce.

Nyarige is finishing her first year at ASU as she works toward a degree in biochemistry and pursuing her dream to become an oncologist. Accessing resources like tutoring centers, libraries, research labs, writing centers and the Sun Devil Fitness Complex has proven invaluable for her.

“I love ASU. I am getting involved on campus and I’m also a student leader,” she said. “They make college comfortable academically and socially, making me feel that I am in the best place.”

The educational institutions that comprise the partnership to date are: African Leadership Academy, the American University of Beirut – Faculty of Health Sciences, Arizona State University, Ashesi University, Duke University, EARTH University, Michigan State University, Stanford University, University of California at Berkeley, Wellesley College, University of Toronto, University of British Columbia, McGill University and two secondary school programs with BRAC and Camfed in Uganda and Ghana.

“Since MasterCard Foundation Scholars all have one common goal, of giving back to society, working with them to realize my dream will be a great step in my journey of making Africa a better place health wise,” Nyarige said. “I love learning about new cultures, and since Africa is so diverse when it comes to culture, learning more will be a great opportunity to expand my understanding of my continent.”

Julie Newberg , julie.newberg@asu.edu
Media Relations

March 21, 2013
ASU scientists develop innovative twists to DNA nanotechnology

In their latest twist to the technology, Yan's team made new 2-D and 3-D objects that look like wire-frame art of spheres as well as molecular tweezers, scissors, a screw, hand fan, and even a spider web.

The Yan lab, which includes colleagues Dongran Han, Suchetan Pal, Shuoxing Jiang, Jeanette Nangreave and assistant professor Yan Liu, published their results in the March 22 issue of Science.

The twist in their 'bottom up,' molecular Lego design strategy focuses on a DNA structure called a Holliday junction. In nature, this cross-shaped double-stacked DNA structure is like the 4-way traffic stop of genetics --- where 2 separate DNA helices temporality meet to exchange genetic information. The Holliday junction is the crossroads responsible for the diversity of life on Earth, and ensures that children are given a unique shuffling of traits from a mother and father's DNA.

In nature, the Holliday junction twists the double-stacked strands of DNA at an angle of about 60-degrees, which is perfect for swapping genes but sometimes frustrating for DNA nanotechnology scientists, because it limits the design rules of their structures.
"In principal, you can use the scaffold to connect multiple layers horizontally," [which many research teams have utilized since the development of DNA origami by Cal Tech's Paul Rothemund in 2006]. However, when you go in the vertical direction, the polarity of DNA prevents you from making multiple layers," said Yan. "What we needed to do is rotate the angle and force it to connect."

Making the new structures that Yan envisioned required re-engineering the Holliday junction by flipping and rotating around the junction point about half a clock face, or 150 degrees. Such a feat has not been considered in existing designs.
"The initial idea was the hardest part," said Yan. "Your mind doesn't always see the possibilities so you forget about it. We had to break the conceptual barrier that this could happen."

In the new study, by varying the length of the DNA between each Holliday junction, they could force the geometry at the Holliday junctions into an unconventional rearrangement, making the junctions more flexible to build for the first time in the vertical dimension. Yan calls the backyard barbeque grill-shaped structure a DNA Gridiron.
"We were amazed that it worked!" said Yan. "Once we saw that it actually worked, it was relatively easy to implement new designs. Now it seems easy in hindsight. If your mindset is limited by the conventional rules, it's really hard to take the next step. Once you take that step, it becomes so obvious."

The DNA Gridiron designs are programmed into a viral DNA, where a spaghetti-shaped single strand of DNA is spit out and folded together with the help of small 'staple' strands of DNA that help mold the final DNA structure. In a test tube, the mixture is heated, then rapidly cooled, and everything self-assembles and molds into the final shape once cooled. Next, using sophisticated AFM and TEM imaging technology, they are able to examine the shapes and sizes of the final products and determine that they had formed correctly.

This approach has allowed them to build multilayered, 3-D structures and curved objects for new applications.

"Most of our research team is now devoted toward finding new applications for this basic toolkit we are making," said Yan. "There is still a long way to go and a lot of new ideas to explore. We just need to keep talking to biologists, physicists and engineers to understand and meet their needs."

Yan's research is funded by several grants from the National Science Foundation, Office of Naval Research, Army Research Office grant and an Army Research Office MURI award, and an ASU Presidential Strategic Initiative Fund. Hao Yan and Yan Liu are part of the Center for Bio-Inspired Solar Fuel Production, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.

Hao Yan is the Milton Glick Chair in the Department of Chemistry and Biochemistry and researcher at ASU's Biodesign Institute.

written by Joe Caspermeyer

March 21, 2013
Enzymes allow DNA to swap information with exotic molecules

The discovery of the Rosetta Stone resolved a longstanding puzzle, permitting the translation of Egyptian hieroglyphs into Ancient Greek.

John Chaput, a researcher at Arizona State University’s Biodesign Institute has been hunting for a biological Rosetta Stone – an enzyme allowing DNA’s 4-letter language to be written into a simpler (and potentially more ancient) molecule that may have existed as a genetic pathway to DNA and RNA in the prebiotic world.

Research results, which recently appeared in the Journal of the American Chemical Society, demonstrate that DNA sequences can be transcribed into a molecule known as TNA and reverse transcribed back into DNA, with the aid of commercially available enzymes.

The significance of the research is three-fold:

• It offers tantalizing clues about how DNA and RNA – which encode the building plans for all earthly life – may have arisen from more primitive information-carrying molecules.

• Contributes to the field of exobiology – the search for alternative life forms elsewhere in the universe.

• Points to possible applications for TNA and other unusual nucleic acid molecules (known as xenonucleic acids or XNAs) in molecular medicine.

In the case of biomedical applications, XNAs may be developed into aptamers—molecular structures that can mimic the properties of naturally occurring polymers, folding into a variety of 3-dimensional forms and binding with selected targets. Aptamers are useful for a range of clinical applications including the development of macromolecular drugs.

“TNA is resistant to nuclease degradation, making it an ideal molecule for many therapeutic and diagnostic applications,” Chaput says.

The structural plans for organisms ranging from bacteria to primates (including humans) are encrypted in DNA using an alphabetic code consisting of just A, C, T & G, which represent the 4 nucleic acids. In addition to their information-carrying role, DNA and RNA possess two defining properties: heredity, (which allows them to propagate their genetic sequences to subsequent generations) and evolution, (which allows successive sequences to be modified over time and to respond to selective pressure).

The chemical complexity of DNA has convinced most biologists that it almost certainly did not arise spontaneously from the prebiotic soup existing early in earth’s history. According to one hypothesis, the simpler RNA molecule may at one time have held dominion as the sole transmitter of the genetic code. RNA is also capable of acting as an enzyme and may have catalyzed important chemical reactions leading eventually to the first cellular life.

But RNA is still a complex molecule and the search for a simpler precursor that may have acted as a stepping-stone to the RNA, DNA and protein system that exists today has been intense.

A variety of xenonucleic acids are being explored as candidates for the role of transitional molecule. In the current study, threose nucleic acid or TNA is investigated. Chaput says that establishing TNA as a progenitor of RNA would require demonstrating that TNA can perform functions that would help support a pre-RNA world. Of particular importance, would have been the ability replicate itself in the absence of protein enzymes.

Like DNA, TNA can form double-helices – spiral staircase structures consisting of the 4 nucleotide bases, which make up the ladder-like rungs, and a sugar and phosphorus backbone, which forms the ladder’s railing. The sugar portion of this backbone is a defining component of the nucleic acid. DNA uses deoxyribose, RNA uses ribose and TNA uses threose.

Both DNA and RNA have sugars containing five carbon atoms, but TNA’s threose sugar contains only four. This enables TNA to assemble from just two identical carbon units, making it far easier to form under the non-biological conditions than RNA or DNA.

Despite TNA’s chemical distinctiveness, it is similar enough to DNA and RNA to be able to interact with these familiar molecules and exchange information. In addition to forming helices, TNA segments can bind with complementary DNA and RNA strands through Watson-Crick base pairing, thus making TNA an alternate self-replicating entity. The study of TNA and other artificially-produced genetic polymers is part of a rapidly emerging discipline known as synthetic genetics.

Powerful tools allow for high-throughput production of molecules with specified traits, built from xenonucleic acid molecules like TNA. In the current study, Chaput and his research team demonstrate that certain commercially available enzymes can facilitate the transcription of DNA sequences into TNA and back again into DNA and that the TNA sequences can be induced to evolve under the influence of environmental cues. The process is known as in vitro selection.

To accomplish this, large pools of TNA molecules are produced from DNA templates and then exposed to a particular molecular target. The small fraction of the random-sequence TNA strands structurally capable of binding with the target are extracted and reverse-transcribed back into DNA, then amplified using polymerase chain reaction (PCR).

The process can be repeated, allowing for significant enrichment of the desired aptamer. Indeed, the authors note that a single round of selection in their experiment produced a 380-fold enrichment from an original library of 1014 DNA templates. The authors note that the method is therefore capable of pinpointing and enriching a particular aptamer of predefined function from a staggering 1015 non-functional sequences. (One potential benefit of constructing aptamers from TNA is improved stability – natural enzymes that rapidly break down DNA and RNA do not degrade them.)

Prior to the current study, researchers had been frustrated that only severely abbreviated lengths of DNA could be faithfully transcribed into TNA. The limiting factor in the process was an effective enzyme to guide the accurate transcription of the DNA message. In the case of normal biological transcription, DNA is transcribed into RNA with the help of a specific enzyme known as DNA polymerase. Such naturally occurring polymerases, Chaput points out, are highly specific, and don’t work well for DNA to TNA transcription or reverse transcription.

Recent advances in protein engineering however, have produced a new breed of synthetic polymerases. In the current study, one of these – known as Therminator DNA polymerase, faithfully transcribed a 70 nucleotide DNA sequence into TNA, while another, known as SuperScript II (SSII) performed reverse-transcription back into DNA with impressively high fidelity. Sequences of both 3-letter and 4-letter DNA messages were transcribed and reverse transcribed, both with over 90 percent accuracy.

The research paves the way for more sophisticated manipulation of TNA and other xenonucleic acids and may strengthen the case that TNA or a closely related molecule set the stage for the emergence of RNA and the first earthly life.

Given the enormous potential for this research for the fields of synthetic biology, exobiology and medicine, it is likely that XNAs will be produced in greater abundance by large chemical laboratories. Currently, the synthesis and purification of nucleoside triphosphates needed to form XNA backbones remains a delicate and labor-intensive process.

Richard Harth, Richard.Harth@asu.edu
The Biodesign Institute

March 13, 2013
Hayes honored for top achievements

The American Microchemical Society will honor Mark Hayes, ASU associate professor of chemistry and biochemistry, with the Benedetti-Pichler Award in recognition of his major contributions to the development of new technology for analyzing ultra small volumes of biological fluids and tissues.

The award recognizes outstanding research in the field of microchemistry as well as administration, teaching and other activities that promote and advance microchemistry. The award will be presented at the Eastern Analytical Symposium and Exhibition in November of this year in Somerset, N.J.

Hayes’s academic career has produced significant results across several disciplines within the analytical and physical chemistry community that includes aspects of engineering, physics, biology and medicine. While contributing to the knowledge base, Mark has energetically and creatively supported the wider profession at local, regional, national and international levels.

“It is an honor to be included in an impressive line of BP Award winners that stretches over four decades,” said Hayes. “I am humbled to be added to any list that includes the likes of Walter C. McCrone (father of modern scientific microscopy), George H. Morrison (a giant in the field and past editor of Analytical Chemistry), Jonathan V. Sweedler (current editor of Analytical Chemistry) and my own research advisor Andrew G. Ewing (Marie Currie Chair, Chalmers University and University of Gothenburg, Sweden). While our group has worked quietly and diligently, it is great to see that our work has been noted and is respected.”

Hayes earned his undergraduate degree at Humboldt State University, in Calif., and then initially worked in private industry at a "mom & pop" analytical laboratory, and at J&W Scientific capillary gas chromatography column manufacturer (now part of Agilent). He then entered graduate school at Penn State University and studied under professor Andrew G. Ewing, developing electroosmotic flow control mechanisms. Postdoctoral studies were with professor Werner Kuhr at the University of California, Riverside and focused on attaching enzymes directly to electrochemical probes to transduce non-electroactive targets to species, which can be sensed via electron transfer.

Hayes has contributed to several different research areas, ranging from creating bionanotubules from liposomes in electric fields, to establishing a framework for vastly improved microscale array-based separations, reported in more than seventy publications and book chapters. He has served on review panels for NIH, NSF, DOE, RSC, NAS, DOJ, GRE, DARPA, private industry, local (Mayo Clinic), and Romanian & Czech scientific and has served as peer reviewer to at least twenty-five journals, including Analytical Chemistry, The Journal of the American Chemical Society, Nature, Langmuir and The Proceedings of the Royal Society. He was recently elected President (starting in 2013) of AES (Electrophoresis Society) and recently was named to the editorial board of Electrophoresis and was a finalist for the FACSS Innovation Award. He has mentored fifty undergraduate and graduate students, producing thirteen doctorates while supporting them with research funds and prestigious fellowships from NSF, ACS, Fulbright, Kirkbright, FLAS and local awards.

Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

Feb 1, 2013
Chaput's artificial DNA work featured as top 2012 story in Discover magazine

For their biomimicry work on creating synthetic, DNA-like genetic materials, an international research team, which includes Arizona State University's John Chaput, has garnered recognition by Discover magazine as one of its top stories of 2012.

All the information necessary for life on Earth is made from just two building blocks, DNA and its chemical cousin RNA. But are there other possibilities to explore?

Chaput wanted to challenge these assumptions and gain insights into the evolution of DNA by creating new molecules that mimicked the core functions of the molecule of life. The team made six types of artificial DNA, called XNAs, that could encode information and build proteins just like DNA. And intriguigingly, XNAs can also evolve.

“What happened here is that a community of scientists came together and organized around this idea that we could find polymerases that could be used to open up biology to unnatural polymers," said Chaput, a Biodesign Institute researcher and associate professor in the Department of Chemistry and Biochemistry, in the College of Liberal Arts & Sciences.

The research group consisted of investigators from the Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, led by Philipp Holliger; the Institute, Katholieke Universiteit Leuven, Belgium, led by Piet Herdewijn; the Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, led by Jesper Wengel; and the Biodesign Institute at Arizona State University, led by John Chaput.

The hopes of the research team is to use these discoveries to gain insights into how early life on Earth evolved and for medical applications such as novel therapeutics.

To learn more:

Discover magazine writer Kat McGowan highlights their work online and in the January/February issue of Discover. The research, which was published April, 2012, in the journal Science, was also featured in Discover and in a Biodesign news release.

Media contact:

Joe Caspermeyer
Managing editor
Biodesign Institute
joseph.caspermeyer@asu.edu
480-727-0369

Female Nephila clavipes on her web. The web was characterized using Brillouin spectroscopy to directly and non-invasively determine the mechanical properties. Photo by: Jeffery Yarger

Feb 1, 2013
ASU scientists unravel the mysteries of spider silk

Scientists at ASU are celebrating their recent success on the path to understanding what makes the fiber that spiders spin – weight for weight – at least five times as strong as piano wire. They have found a way to obtain a wide variety of elastic properties of the silk of several intact spiders’ webs using a sophisticated but non-invasive laser light scattering technique.

“Spider silk has a unique combination of mechanical strength and elasticity that make it one of the toughest materials we know,” said Jeffery Yarger, a professor in ASU’s Department of Chemistry and Biochemistry and lead researcher of the study. “This work represents the most complete understanding we have of the underlying mechanical properties of spider silks.”

Spider silk is an exceptional biological polymer, related to collagen (the stuff of skin and bones) but much more complex in its structure. The ASU team of chemists is studying its molecular structure in an effort to produce materials ranging from bulletproof vests to artificial tendons.

The extensive array of elastic and mechanical properties of spider silks in situ, obtained by the ASU team, is the first of its kind and will greatly facilitate future modeling efforts aimed at understanding the interplay of the mechanical properties and the molecular structure of silk used to produce spider webs.

The team published their results in today’s advanced online issue of Nature materials and their paper is titled “Non-invasive determination of the complete elastic moduli of spider silks.”

“This information should help provide a blueprint for structural engineering of an abundant array of bio-inspired materials, such as precise materials engineering of synthetic fibers to create stronger, stretchier and more elastic materials,” explained Yarger.

Other members of Yarger’s team, in ASU’s College of Liberal Arts and Sciences, included Kristie Koski, at the time a postdoctoral researcher and currently a postdoctoral fellow at Stanford University, and ASU undergraduate students Paul Akhenblit and Keri McKiernan.

The Brillouin light scattering technique used an extremely low power laser, less than 3.5 milliwatts, which is significantly less than the average laser pointer. Recording what happened to this laser beam as it passed through the intact spider webs enabled the researchers to spatially map the elastic stiffnesses of each web without deforming or disrupting it. This non-invasive, non-contact measurement produced findings showing variations among discrete fibers, junctions and glue spots.

Four different types of spider webs were studied. They included Nephila clavipes (pictured), A. aurantia (“gilded silver face”-common to the contiguous United States), L. Hesperus, the western black widow and P. viridans, the green lynx spider, the only spider included that does not build a web for catching prey but has major silk elastic properties similar to those of the other species studied.

The group also investigated one of the most studied aspects of orb-weaving dragline spider silk, namely supercontraction, a property unique to silk. Spider silk takes up water when exposed to high humidity. Absorbed water leads to shrinkage in an unrestrained fiber up to 50 percent shrinkage with 100 percent humidity in N. clavipes silk.

Their results are consistent with the hypothesis that supercontraction helps the spider tailor the properties of the silk during spinning. This type of behavior, specifically adjusting mechanical properties by simply adjusting water content, is inspirational from a bio-inspired mechanical structure perspective.

“This study is unique in that we can extract all the elastic properties of spider silk that cannot and have not been measured with conventional testing,” concluded Yarger.

The Department of Defense and the National Science Foundation supported this research.

Media source:
Jeffery Yarger, jyarger@gmail.com
480-965-0673

Part of the ASU team of scientists involved in the work: (from left to right) Christopher Kupitz, Dingjee Wang, Nadia Zatsepin, John Spence, Petra Fromme and Raimund Fromme. Other members of the ASU team (not in the photo) include Bruce Doak, Uwe Weierstall, Ingo Grotjohann, Tzu-Chiao Chao, Mark Hunter and Richard Kirian. Photo by: Mary Zhu

Jan 13, 2013
ASU research makes Science's top 10 breakthroughs

ASU scientists have been lauded by the journal Science, which cited their groundbreaking research on protein structures as one of the top 10 breakthroughs of 2012.

Working as part of an international team, the ASU researchers have been central to the technological developments leading to a stream of exciting discoveries since 2009 – the most recent of which were reported in a November 2012 edition of Science.

For the first time, the scientists determined the three dimensional structure of a protein by the method of femtosecond nanocrystallography, a highly innovative technique that was developed by the team at ASU and their collaborators using X-ray laser diffraction from the LCLS free-electron laser.

Contradictory to popular opinion, this technique successfully demonstrates that high quality data can be acquired so quickly that reaction chemistry involving proteins can now be studied in real time. This method goes well beyond form, but goes into function where changes in a molecule can be seen in action.

“The ASU team is one of the pioneers of the method of fs crystallography," said ASU Regents' Professor John Spence. "Our work includes the design of a sample delivery system, the identification and discovery of nanocrystals, as well as the development of the theory and computer algorithms used to analyze the data. The method is so exciting as its further development will allow us to determine movies of molecular machines at work."

The technique – described in the paper “High-resolution protein structure determination by serial femtosecond crystallography” – works at a higher resolution than previously achieved using X-ray lasers, allowing scientists to use smaller crystals than typical with other methods that grow inside living cells, and could enable researchers to view molecular dynamics at a time-scale never observed before. SLAC’s Linac Coherent LightSource (LCLS) shines a billion times brighter than traditional synchrotron X-ray sources.

Science stated that “the grand goal is to push X-ray diffraction to its ultimate limit and use an X-ray laser to decipher a protein structure by zapping individual molecules.” According to Science, the success of the study "shows the potential of X-ray lasers to decipher proteins that conventional X-ray sources cannot.”

Advancements in this research may be of great importance for the development of new drugs to fight African sleeping sickness, which kills approximately 30,000 people each year. This method shows novel features of the structure of the CatB protein, a protease that is essential for the pathogenesis, including the structure of the natural inhibitor peptide bound in the catalytic cleft of the enzyme. The discovery of the enzyme’s 3D structure has enabled the researchers to pinpoint distinctive structural differences between the human and the parasite’s form of the enzyme.

The research is accomplished by a large international team which involves, in addition to ASU, key institutions including the Center of Free-Electron Laser Science at DESY in Hamburg, University of Luebeck, who grew the crystals of CatB and the Max Plank Institute in Heidelberg. Henry Chapman from the Center of Free-Electron Laser Science led the team of scientists for this study.

ASU contributors include the research groups of Spence, Bruce Doak and Uwe Weierstall from the Department of Physics, and Galvin Professor Petra Fromme from the Department of Chemistry and Biochemistry, all part of the College of Liberal Arts and Sciences.

“In 2009 we showed the first proof of principle after the world’s first high-energy free-electron laser had become operational in Stanford,” said Fromme. “This leading technology will revolutionize the field of structural biology.”

“This research would not have been possible without the liquid jet injector for the nanocrystals developed at ASU (patent has been filed) nor the biochemical expertise that led to success in the preceding measurements, which laid the groundwork for the Trypanosoma work,” said Doak, professor from ASU’s Department of Physics.

The project depends on the excellent team of ASU’s research scientists, postdoctoral researchers and graduate students from Physics and Chemistry who work at ASU and travel with their professors to conduct the experiments at Stanford at the LCLS free-electron laser. These include faculty research associates Raimund Fromme, Ingo Grotjohann and Tzu-Chiao Chao; Nadia Zatsepin, post-doctoral researcher, graduate students Christopher Kupitz (Biochemistry) and Dingjie Wang (Physics); as well as Mark Hunter and Richard Kirian who graduated with PhDs from ASU in Chemistry and Physics respectively and now work on the femtosecond crystallography project at Lawrence Livermore National Laboratory and DESY (Deutsches Elektronen Synchrotron).

“ASU is proud of the achievements and dedication of these scientists for their innovative work in producing high-quality and groundbreaking discoveries that advance use-inspired research to combat disease,” said William Petuskey, associate vice president of natural/physical sciences and engineering/technology for ASU’s Office of Knowledge Enterprise Development. “This breakthrough will help pave the way for further advancements in biomedical research.”

The ASU team was awarded a patent for the sample delivery system, which uses microscopic (and even nanoscopic) liquid jets to inject samples into the X-ray beam.
Amelia Huggins, amelia.huggins@asu.edu
480-965-1754
Office of Knowledge Enterprise Development

Geraldine Richmond has distinguished herself in her research using nonlinear optical spectroscopy and computational methods applied to understanding the chemistry that occurs at complex surfaces and interfaces that have relevance to important problems in energy production, environmental remediation, atmospheric chemistry and biomolecular surfaces. Over 180 publications have resulted from this research.

Richmond is the Richard M. and Patricia H. Noyes Professor in the Department of
Chemistry at the University of Oregon. She received her bachelor's degree in chemistry from Kansas State University (1975) and her Ph.D. in chemical physics at the University of California, Berkeley (1980) where worked under the mentorship of Professor George Pimentel.

Recent awards for her scientific accomplishments include the American Chemical Society (ACS) Garvan Medal (1996), the Oregon Scientist of the Year by the Oregon Academy of Science (2001), the Spectrochemical Analysis Award of the American Chemical Society (2002), the Spiers Medal of the Royal Society of Chemistry (2004), a Guggenheim Fellow (2007) the Bomem-Michaelson Award (2008) and the ACS Joel Henry Hildebrand Award in the Theoretical and Experimental Chemistry of Liquids (2011) and the American Physical Society (APS) Davisson-Germer Prize for Atomic or Surface Physics (2013). She is a Fellow of the American Physical Society, the American Chemical Society, the American Association of the Advancement of Science (AAAS), and the Association for Women in Science (AWIS) and the Association of Applied Spectroscopy. She is a member of both the American Academy of Arts and Sciences and the U.S. National Academy of Sciences.

Professor Richmond has also played an important role in setting the national scientific agenda
through her service on many science boards and advisory panels. Most recent appointments include a Member of the National Science Board (2012-2018), Member and Vice-Chair of the Secretary of Energy’s Hydrogen and Fuel Cell Advisory Committee, Associate Editor of Annual Reviews of Physical Chemistry (2006-2010), Chair of the Science Advisory Committee of the Stanford Synchrotron Radiation Laboratory (2006-2008), Chair of the Chemistry Section, Association for the Advancement of Science (AAAS) (2009-2010), Chair of the Basic Energy Sciences Advisory Board of the Department of Energy (1998-2003) and as a governor appointee to the State of Oregon Board of Higher Education where she served as a member, Vice President and interim President over her seven year term (1999-2006). She has testified on science issues before committees in the U.S. Senate, the U.S. House of Representatives and the Oregon House of Representatives.

She is the founder and chair of COACh, a grass-roots organization assisting in the advancement of women scientists in both the U.S. and in developing countries (http://coach.uoregon.edu). Over 7000 science faculty, researchers, students, postdocs and administrators have benefited from professional training and networking workshops that she has helped design and conduct. Her COACh international efforts include projects in Tunisia, Morocco, Mozambique, Algeria, Kenya, Cameroon, Gabon South Africa, Korea, China, Chile, Brazil and Mexico, For these efforts she has been awarded the Presidential Award for Excellence in Science and Engineering Mentoring (1997), the American Chemical Society Award for Encouraging Women in the Chemical Sciences (2005), the Council on Chemical Research Diversity Award (2006) and the American Chemical Society Charles L.Parsons Award (2013).

More...

Scientists found treasure when they studied a meteorite that was recovered April 22, 2012 at Sutter's Mill, the gold discovery site that led to the 1849 California Gold Rush. Detection of the falling meteorites by Doppler weather radar allowed for rapid recovery so that scientists could study for the first time a primitive meteorite with little exposure to the elements, providing the most pristine look yet at the surface of primitive asteroids.

An international team of 70 researchers, including Sandra Pizzarello from ASU’s Department of Chemistry and Biochemistry, reported in the December 21 issue of Science that this meteorite was classified as a Carbonaceous Chondrite (Mighei or CM-type) and that they were able to identify for the first time the source region of these meteorites.

"The small three meter-sized asteroid that impacted over California’s Sierra Nevada came in at twice the speed of typical meteorite falls," said lead author and meteor astronomer Peter Jenniskens of the SETI Institute, Mountain View, Calif., and NASA Ames Research Center, Moffett Field, Calif. "Clocked at 64,000 miles per hour, it was the biggest impact over land since the impact of the four meter-sized asteroid 2008 TC3, four years ago over Sudan."

Pizzarello studied both the soluble and insoluble organic materials in the meteorite and explained that, “While not containing as many compounds as other meteorites, for example the Murchison meteorite, it still offers a fascinating view of the cosmochemical evolution of the biogenic elements in the Solar System.”

The asteroid approached on an orbit which points to the source region of CM chondrites. From photographs and video of the fireball, Jenniskens calculated that the asteroid approached on an unusual low-inclined almost comet-like orbit that reached the orbit of Mercury, passing closer to the sun than known from other recorded meteorite falls.

"It circled the sun three times during a single orbit of Jupiter, in resonance with that planet," Jenniskens said. Based on the unusually short time that the asteroid was exposed to cosmic rays, there was not much time to go slower or faster around the sun. That puts the original source asteroid very close to this resonance, in a low inclined orbit.

"A good candidate source region for CM chondrites now is the Eulalia asteroid family, recently proposed as a source of primitive C-class asteroids in orbits that pass Earth," adds Jenniskens. After the asteroid broke up in the atmosphere, weather radar briefly detected a hailstorm of falling meteorites over the townships of Coloma and Lotus in California.

adapted from NASA’s press release by Karen Jenvey

Dec 27, 2012
Strange behavior: new study exposes living cells to synthetic protein

One approach to understanding components in living organisms is to attempt to create them artificially, using principles of chemistry, engineering and genetics. A suite of powerful techniques – collectively referred to as synthetic biology – have been used to produce self-replicating molecules, artificial pathways in living systems and organisms bearing synthetic genomes.

In a new twist, John Chaput, a researcher at Arizona State University’s Biodesign Institute, and colleagues at the Department of Pharmacology, Midwestern University, in Glendale, Ariz., have fabricated an artificial protein in the laboratory and examined the surprising ways living cells respond to it.

“If you take a protein that was created in a test tube and put it inside a cell, does it still function?” Chaput asks. “Does the cell recognize it? Does the cell just chew it up and spit it out?” This unexplored area represents a new domain for synthetic biology and may ultimately lead to the development of novel therapeutic agents.

The research results, reported in the advanced online edition of the journal ACS Chemical Biology, describe a peculiar set of adaptations exhibited by Escherichia coli bacterial cells exposed to a synthetic protein, dubbed DX. Inside the cell, DX proteins bind with molecules of ATP, the energy source required by all biological entities.

“ATP is the energy currency of life,” Chaput says. The phosphodiester bonds of ATP contain the energy necessary to drive reactions in living systems, giving up their stored energy when these bonds are chemically cleaved. The depletion of available intracellular ATP by DX binding disrupts normal metabolic activity in the cells, preventing them from dividing, (though they continue to grow).

After exposure to DX, the normally spherical E. coli bacteria develop into elongated filaments. Within the filamentous bacteria, dense intracellular lipid structures act to partition the cell at regular intervals along its length (see figure 1). These unusual structures, which the authors call endoliposomes, are an unprecedented phenomenon in such cells.

“Somewhere along the line of this filamentation, other processes begin to happen that we haven’t fully understood at the genetic level, but we can see the results phenotypically,” Chaput says. “These dense lipid structures are forming at very regular regions along the filamented cell and it looks like it could be a defense mechanism, allowing the cell to compartmentalize itself.” This peculiar adaptation has never been observed in bacterial cells and appears unique for a single-celled organism.

Producing a synthetic protein like DX, which can mimic the elaborate folding characteristics of naturally occurring proteins and bind with a key metabolite like ATP is no easy task. As Chaput explains, a clever strategy known as mRNA display was used to produce, fine-tune and amplify synthetic proteins capable of binding ATP with high affinity and specificity, much as a naturally occurring ATP-binding protein would.

First, large libraries of random sequence peptides are formed from the four nucleic acids making up DNA, with each strand measuring around 80 nucleotides in length. These sequences are then transcribed into RNA with the help of an enzyme – RNA polymerase. If a natural ribosome is then introduced, it attaches to the strand and reads the random sequence RNA as though it was a naturally-occurring RNA, generating a synthetic protein as it migrates along the strand. In this way, synthetic proteins based on random RNA sequences can be generated.

Exposing the batch of synthetic proteins to the target molecule and extracting those that bind can then select for ATP-binding proteins. But as Chaput explains, there’s a problem: “The big question is how do you recover that genetic information? You can’t reverse transcribe a protein back into DNA. You can’t PCR amplify a protein. So we have to do all these molecular biology tricks.”

The main trick involves an earlier step in the process. A molecular linker is chemically attached to the RNA templates, such that each RNA strand forms a bond with its newly translated protein. The mRNA-protein hybrids are exposed to selection targets (like ATP) over consecutive rounds of increasing stringency. After each round of selection, those library members that remain bound to the target are reverse-transcribed into cDNA (using their conveniently attached RNA messages), and then PCR amplified.

In the current study, E. coli cells exposed to DX transitioned into a filamentous form, which can occur naturally when such cells are subject to conditions of stress. The cells display low metabolic activity and limited cell division, presumably owing to their ATP-starved condition.

The study also examined the ability of E. coli to recover following DX exposure. The cells were found to enter a quiescent state known as viable but non-culturable (VBNC), meaning that they survived ATP sequestration and returned to their non-filamentous state after 48 hours, but lost their reproductive capacity. Further, this condition was difficult to reverse and seems to involve a fundamental reprogramming of the cell.

In an additional response to DX, the filamentous cells form previously undocumented structures, which the authors refer to as endoliposomes. These dense lipid concentrations, spanning the full width of the filamented E. coli, segment the cells into distinct compartments, giving the cells a stringbean-like appearance under the microscope.

The authors speculate that this adaptation may be an effort to maintain homeostasis in regions of the filamentous cell, which have essentially been walled off from the intrusion of ATP-depleting DX. They liken endoliposomes to the series of water-tight compartments found in submarines which are used to isolate damaged sections of the ship and speculate that DX-exposed cells are partitioning their genetic information into regions where it can be safely quarantined. Such self-compartmentalization is known to occur in some eukaryotic cells, but has not been previously observed in prokaryotes like E. coli.

The research indicates that there is still a great deal to learn about bacterial behavior and the repertoire of responses available when such cells encounter novel situations, such as an unfamiliar, synthetic protein. The study also notes that many infectious agents rely on a dormant state, (similar to the VBNC condition observed in the DX-exposed E. coli), to elude detection by antibiotics. A better understanding of the mechanisms driving this behavior could provide a new approach to targeting such pathogens.

The relative safety of E. coli as a model organism for study may provide a fruitful tool for more in-depth investigation of VBNC states in pathogenic organisms. Further, given ATP’s central importance for living organisms, its suppression may provide another avenue for combating disease. One example would be an engineered bacteriophage capable of delivering DX genes to pathogenic organisms.

In addition to his appointment at the Biodesign Institute, John Chaput is an associate professor in the Department of Chemistry and Biochemistry, in the College of Liberal Arts & Sciences

Richard Harth, Richard.Harth@asu.edu
The Biodesign Institute

An international team of scientists, using the world’s most powerful X-ray laser, has revealed the three dimensional structure of a key enzyme that enables the single-celled parasite that causes African trypanosomiasis (or sleeping sickness) in humans.

With the elucidation of the 3D structure of the cathepsin B enzyme, it will be possible to design new drugs to inhibit the parasite (Trypanosoma brucei) that causes sleeping sickness, leaving the infected human unharmed.

The research team, including several ASU scientists, is led by the German Electron Synchrotron (DESY) scientist Henry Chapman from the Center of Free-Electron Laser Science (CFEL), professor Christian Betzel from the University of Hamburg and Lars Redecke from the SIAS joint Junior Research Group at the Universities of Hamburg and Lübeck. They report their findings this week in Science.

"This is the first new biological structure solved with a free-electron laser," said Chapman of the development.

"These images of an enzyme, which is a drug target for sleeping sickness, are the first results from our new ‘diffract-then-destroy’ snapshot X-ray laser method to show new biological structures which have not been seen before,” explained John Spence, ASU Regents’ Professor of Physics. “The work was led by the DESY group and used the Linac Coherent Light Source at the U.S. Department of Energy’s SLAC National Accelerator Laboratory."

Transferred to its mammalian host by the bite of the tsetse fly, the effects of the parasite are almost always fatal if treatment is not received. The sleeping sickness parasite threatens more than 60 million people in sub-Saharan Africa and annually kills an estimated 30,000 people. Current drug treatments are not well tolerated, cause serious side effects and the parasites are becoming increasingly drug resistant.

“This paper is so exciting as it is based on nanocrystals grown by the groups at DESY in Hamburg and at the University of Lübeck inside living insect cells,” said Petra Fromme, a professor in ASU’s Department of Chemistry and Biochemistry. “This is the first novel structure determined by the new method of femtosecond crystallography. The structure may be of great importance for the development of new drugs to fight sleeping sickness, as it shows novel features of the structure of the CatB protein, a protease that is essential for the pathogenesis, including the structure of natural inhibitor peptide bound in the catalytic cleft of the enzyme.”

An additional difficulty includes the fact that the cathepsin B enzyme is also found in humans and all mammals. However the discovery of the enzyme’s 3D structure has enabled the researchers to pinpoint distinctive structural differences between the human and the parasite’s form of the enzyme. Subsequent drug targets can selectively block the parasite’s enzyme, leaving the patient’s intact.

In addition to Spence and Fromme, other ASU members of the team are Bruce Doak, professor of physics; Uwe Weierstall, research professor in physics; faculty research associates Raimund Fromme, Ingo Grotjohann and Tzu-Chiao Chao; Nadia Zatsepin, post-doctoral researcher, graduate students Christopher Kupitz (Biochemistry), D. Wang (Physics) and Mark Hunter and Richard Kirian who graduated with Ph.D.s from ASU in Chemistry and Physics respectively and now work on the femtosecond crystallography project at Lawrence Livermore National Laboratory and DESY.

The ASU group developed the sample delivery system, worked on the characterization of the crystals with dynamic light scattering and SONNIC and did the early development work on the new data analysis method. All ASU participants are members of the College of Liberal Arts & Sciences.

International team members in addition to those already mentioned include researchers from the Max Planck Institute, Heidelberg, University of Gothenburg, University of Tübingen and Lawrence Livermore National Laboratory.

Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

ASU researcher Dan Buttry and graduate students Mohammad Hasani, Poonam Singh (research associate) and Helme Castro (from left to right). Buttry will use his ARPA-E grant to develop an efficient and cost-effective carbon capture technology using an innovative electrochemical technique. Photo by: Mary Zhu

Nov 30, 2012
Energy grant to help ASU advance carbon capture technology

Scientists to tame power plants by efficiently capturing carbon emissions

The U.S. Department of Energy has awarded Arizona State University a grant for alternative energy research that is part of a special DOE program to pursue high-risk, high-reward advances with the potential to change the way the nation generates and consumes energy.

The grant, led by Dan Buttry, professor and chair of ASU’s Department of Chemistry and Biochemistry, in the College of Liberal Arts and Sciences, is to develop an efficient and cost-effective carbon capture technology using an innovative electrochemical technique. ASU will separate carbon dioxide from other emissions coming from power plants with the real possibility of reducing energy and cost requirements by more than half. This could be an economically enabling breakthrough in the drive to reduce carbon dioxide emissions.

“Through this type of venture we are working to advance research and spur economic development in the areas of renewable energy and energy security to create solutions that address society’s grand challenges,” said Sethuraman “Panch” Panchanathan, senior vice president for ASU’s Office of Knowledge Enterprise Development. “This innovative project is a collaborative effort of faculty at ASU from multiple disciplines who are developing a new carbon capture technology.”

DOE’s Advanced Research Projects Agency-Energy (ARPA-E) program has the goal of developing clever and creative approaches to transform the global energy landscape, while advancing America’s technology leadership. ASU’s grant is for $612,000 for one year.

In announcing the awards, U.S. Energy Secretary Steven Chu said: “With ARPA-E and all of the Department of Energy’s research and development efforts, we are determined to attract the best and brightest minds at our country’s top universities, labs and businesses to help solve the energy challenges of this generation. The 66 projects selected today represent the true mission of ARPA-E: swinging for the fences and trying to hit home runs to support development of the most innovative technologies and change what’s possible for America’s energy future.”

Inspired by the Defense Advanced Research Projects Agency, ARPA-E was created to support high-risk, high-reward research that can provide transformative new solutions for climate change and energy security. The projects were selected through a merit-based process from thousands of concept papers and hundreds of full applications. The projects are based in 24 states, with approximately 47 percent of the projects led by universities, according to the DOE in a Nov. 28 release announcing the awards.

ASU has been building up its portfolio in alternative energy research for several years and currently includes, among its capabilities, a center for research into electrochemistry for renewable energy applications; several advanced programs on solar energy research; one of the leading testing and certification centers for solar energy; and research into solar-generated biofuels including advanced work on algae-based biofuels.

“The potential of this project to advance solutions to the problem of excessive carbon dioxide in the environment is exciting and we look forward to the team’s progress in this area,” said Gary Dirks, director of ASU LightWorks. “ASU is a place where the convergence of laboratory research and real-world application creates a unique environment where imaginative energy-related projects are fostered and encouraged.”

The carbon capture program was initially supported by ASU LightWorks, which brings together the intellectual expertise across the university centered on leveraging the power of the sun to create solutions in the areas of renewable energy, including generating electricity, alternative fuels and preparing future energy leaders.

“We are extremely excited about this new grant from the Department of Energy ARPA-E program," said lead ASU researcher Dan Buttry. "The effort is focused on a key issue in fossil fuel-based energy production – how to reduce atmospheric carbon dioxide emissions without consuming too much of the energy content of the fuel. We have recently developed a new approach to carbon dioxide capture that uses an electrochemical process with some design features similar to those in a fuel cell.”

Co-principal investigators on this project are Cody Friesen, SEMTE-Ira A. Fulton Schools of Engineering; Vladimiro Mujica, Department of Chemistry and Biochemistry; and Ellen Stechel, Department of Chemistry and Biochemistry and also deputy director of LightWorks. Buttry and Friesen previously worked on an ARPA-E project developing a radical new design for automotive batteries.

The only proven commercially viable technology for flue gas capture uses compounds called amines in the so-called monoethanolamine (MEA) process. Several plant scale demonstrations use this old technology, first patented in 1930. The MEA process has several drawbacks, particularly the energy required for thermal regeneration of the amine capture agent. As discussed in a recent Department of Energy report (DOE/NETL-2009/1366), for typical conditions, the energy required for this process consumes roughly 40 percent of total plant output and increases the cost of electricity by 85 percent.

Buttry sees their current approach as having an overall efficiency far better than existing approaches.

“While there are many interesting basic science questions about how the separation works, the ARPA-E program’s emphasis on rapid implementation of technologies will have us running our fastest to accomplish the 'proof of concept' program goals in the 12-month grant period," Buttry said. "Fortunately, we have assembled a terrific team from ASU’s Department of Chemistry and Biochemistry, ASU LightWorks and the Fulton Schools of Engineering to hit the ground running.

"What we hope to accomplish is a demonstration of efficient and cost-effective carbon dioxide capture so we can move into a second phase of the project that would involve rolling the technology out into the marketplace.”

Written by Jenny Green

Media contact:
Amelia Huggins, (480) 965-1754
amelia.huggins@asu.edu
Office of Knowledge Enterprise Development
Arizona State University

Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

Valentin Dinu (left) and Joshua LaBaer

Nov 30, 2012
New collaboration targets rare, deadly malignancy

Desmoplastic small round cell tumor (DSRCT) is a devastating variety of cancer, predominately striking boys and young adults. The exact causes of this rare disease remain shadowy, though the prognosis is bleak. Fewer than 20 percent of those diagnosed survive for more than 5 years.

Now Valentin Dinu, a researcher at Arizona State University and specialist in bioinformatics and Joshua LaBaer, two members of the Virginia G. Piper Center for Personalized Diagnostics at the Biodesign Institute have teamed up with Pooja Hingorani, an oncology/hematology physician at Phoenix Children’s Hospital, to explore the underpinnings of DSRCT with unprecedented precision. Their insights will hopefully pave the way for the design of novel therapeutic agents to treat this deadly disease.

The new project is funded by a 3 year, $250K grant from Hyundai Hope on Wheels, a nonprofit organization, committed to the fight against pediatric cancer. Since its inception in 1998, Hyundai Hope on Wheels has donated $48 million to fund pediatric cancer research nationwide.

The lion’s share of the new award will be used to conduct next generation sequencing of the genomes derived from DSRCT pediatric tumor samples and to perform bioinformatic analyses of the resulting data.

“We are very grateful to the Hyundai Hope on Wheels organization for financially supporting this research project,” Dinu says. “We look forward to working closely with our collaborators from Phoenix Children’s Hospital and the Biodesign Institute to study the biology of DSRCT by applying some of the most advanced genomics sequencing and informatics techniques. Our ultimate goal is to develop improved diagnostic and treatment options for this devastating malignancy that affects young adolescents.”

The Department of Biomedical Informatics (BMI) at ASU is engaged in a number of significant area partnerships, uniting academic researchers, clinical practitioners and regional health care providers. The department recently moved to its new home on the Scottsdale campus of Mayo Clinic as part of the university’s deepening ties with Mayo in health care, medical research and education. Here, Dinu will carry out the informatics and data analysis work.

LaBaer will perform the genomic sequencing at the Center for Personalized Diagnostics at Biodesign, an institute devoted to developing new diagnostic tools to pinpoint the molecular manifestations of disease based on individual patient profiles.

Using their combined expertise, the researchers hope to open a new window onto the particular genomic aberrations linked with DSRCT. “We are very excited about the opportunity to study the underlying genomics of this difficult disease that affects children,” LaBaer says. “The power of these new genome scale sequencing methods will fundamentally alter our understanding of how these cancers begin and how they change over time.”

Desmoplastic small-round-cell tumor is an aggressive, soft tissue sarcoma, typically causing the formation of masses in the abdomen, though affected areas may also include bone, soft tissue, lung, ovary, kidney and central nervous system. The cell origin for the disease is still unknown though it is believed to arise from the mesenchyme.

The malignancy may metastasize from its original site to the liver, lungs, lymph nodes, brain, skull, and bones. DSRCT is 4 times as likely to occur in males and its occurrence in females may be mistaken for ovarian cancer. The incidence of DSRCT is also higher in African-Americans than Caucasians.

The researchers explain that the rareness of the disease has thus far precluded comprehensive studies of DSRCT biology, hence a lack of clinically relevant targets on which to base an effective therapy. The goal of the proposed study is to identify novel genetic aberrations in DSRCTs through the use of next generation genomic sequencing (NGS) technology.

Since the first successful draft of the human genome was released in 2000, the race has been on to find cheaper and more rapid techniques. The new armament of technologies involves strategies to parallelize the sequencing process, enabling researchers to concurrently sequence hundreds of millions of genomic fragments at a time, generating tens of billions of base reads per experiment.

NGS will allow Dinu and LaBaer to mine vital information from the genomes derived from DSRCT-positive samples, revealing copy number changes, allelic aberrations, somatic rearrangements and base pair mutations, producing an enormous quantity of genomic sequence data. Costs associated with whole genome sequencing have recently plummeted, permitting the design and execution of studies capable of rapidly pinpointing potential disease-associated genetic variants. The technique has been used successfully to identify genetic abberations in such diseases as pancreatic cancers, glioblastoma multiforme, lung cancer, ovarian cancer and breast cancer.

Dinu and LaBaer insist the time is ripe to apply such methods to less common (yet lethal) forms of cancer, including DSRCT in order to uncover therapeutic candidates and improve the chances for patients stricken with such diseases. The team will perform whole genome DNA and RNA sequencing on tumor samples and their corresponding matched normal samples, in order to identify novel mutations, single nucleotide polymorphisms or other genomic aberrations associated with these tumors.

The researchers stress that while the sample size used for the current project is small, the enormous volume of genomic data acquired should allow a positive identification of variants implicated in the disease. A collection of these variants – identified in DSRCT samples but absent in normal tissue – will act as biomarkers for the disease and may be applied for earlier and more accurate diagnostic purposes, as well as to provide plausible targets for future treatment. The group’s results will be cross-checked and validated using additional testing methods, such as Sanger sequencing or quantitative PCR.

Valentin Dinu is assistant professor in the Department of Biomedical Informatics at ASU and faculty member of the Virginia G. Piper Center for Personalized Diagnostics at ASU’s Biodesign Institute.

Joshua LaBaer directs the Virginia G. Piper Center for Personalized Diagnostics at ASU’s Biodesign Institute and is a professor in the School of Liberal Arts and Sciences, Chemistry and Biochemistry

Richard Harth, Richard.Harth@asu.edu
The Biodesign Institute

Image Credit: Michael Vaughn

Nov 9, 2012
Hydrogenase mimics for solar fuel production

One of the challenges of our times is undoubtedly the development of a clean, sustainable source of energy to replace the current, unsustainable dependency on fossil fuels. In this context, hydrogen has been proposed as a possible substitute. In Nature, hydrogen metabolism evolves through the hydrogenases, a class of enzymes found in several microorganisms that catalyze proton reduction and hydrogen oxidation reversibly under mild conditions.

The relevance of this reaction to energy production has spurred considerable interest around these enzymes, with particular emphasis on the development of biologically inspired hydrogen-production catalysts. Here at ASU the Bio-Inspired Solar Fuel Production Center is spearheading the conversion of solar energy to hydrogen; Subtask 3 in particular focuses on the development of bioinspired hydrogen production catalysts. In work featured this month on the inside cover of Chemical Communications, the Ghirlanda lab demonstrated photoinduced hydrogen production in water, using an artificial protein model of the hydrogenase.

The catalytic site of hydrogenases, termed the H-cluster, is very complex. In the diiron hydrogenases, it is composed of a [4Fe4S] cluster and a [FeFe] site coordinated by a non-protein dithiolate bridging ligand as well as carbon monoxide (CO) and cyanide (CN) ligands. The site is anchored to the protein through a cysteine that bridges the proximal iron-sulfur cluster and one iron. Such an unusual cluster is assembled in vivo through specialized biosynthetic machinery. For these reasons, direct engineering of natural hydrogenases has proven to be a daunting task.

Over the years, work on organometallic model compounds has elucidated several features that characterize the catalytic cycle of the diiron site. Of the hundreds of organometallic model compounds developed, several demonstrate moderate catalytic activity, albeit with rates much slower than the natural enzymes, under significantly harsher conditions (typically in organic or organic/aqueous co-solvents and strong acids), and with unfavorable energetics (high overpotentials). The differences in activity between the natural enzymes and the organometallic complexes are ascribed to the protein matrix, which in the hydrogenases stabilizes the catalytically active “rotated” conformation of the distal iron and facilitates the reaction by rapidly transferring electrons and a proton to the active site.

Rather than utilizing an organometallic complex, graduate student Anindya Roy pursued an alternative approach that utilizes an artificial amino acid as an anchor to covalently secure the diiron–cluster at any position in a designed protein scaffold. Cluster incorporated peptide motif was analyzed by UV-Vis, FTIR and ESI-MS and CD spectroscopy. Anindya then enlisted Chris Madden (Gust group) as collaborator for functional studies. Together they found that the complex, 1-[Fe2(CO)6], catalyses photo-induced hydrogen production in the presence of a photosensitizer and a sacrificial reducing agent in water with remarkable efficiency. This approach allows for the directed incorporation of hydrogenase mimics into any peptide scaffold and opens the way for the design of more elaborate peptide-based architectures. With such artificial proteins, it will be possible to explore the effect of second sphere interactions on the activity of the diiron center, and to include in the design properties such as compatibility with conductive materials and electrodes.

“Photo-induced hydrogen production in a helical peptide incorporating a [FeFe] hydrogenase active site mimic” Roy A., Madden C., and Ghirlanda G. Chemical Communications (2012) 48, 9816-18

An elegant analysis of protein assembly

Today's "New and Notable" article by Yves Engelborghs in the Biophysical Journal describes an enthusiastically reviewed study of protein self-assembly by associate professors Marcia Levitus and Rebekka Wachter and coworkers from ASU's Department of Chemistry and Biochemistry.

The analysis of the polymerization of protein subunits is an old challenge that has never lost its importance. In fact this process could be a key to biological control. "Likewise, an increasing number of diseases are related to aberrant protein oligo- and polymerization," described Engelborghs.

“In land plants, Rubisco activase regulates the extent of atmospheric carbon fixation by coordinating the light and dark reactions of photosynthesis. Although protein self-association plays a critical role in this process, the activase assembly mechanism has remained elusive for many years,” explained Wachter.

Despite the significance of the problem, the assembly pathway of Rubisco activase has been difficult to track due to the different states of oligomerization of the proteins observed in these preparations. In this work, the authors used fluorescence techniques that rely on the measurement and analysis of very small numbers of molecules.

"These techniques are convenient ways to study molecular diffusion and oligomerization without physical perturbation of the sample in a wide range of concentrations. Our results show clear evidence of the coexistence of multiple oligomerization states, and allowed us to propose possible mechanisms for the subunit association pathways of Rubisco activase," stated Levitus who is also part of the Center of Single Molecule Biophysics in ASU's Biodesign Institute. "In addition, the methodology that we developed in this work can be broadly used to investigate self-association in other proteins."
Article source:
Biophysical Journal - "New and Notable"

Article:
http://www.cell.com/biophysj/fulltext/S0006-3495(12)01063-6

Editor's Note: Links are included for informational purposes only. Due to varying editorial policies, news publications may remove or change a link for archival purposes at any time without notice.

Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

E. U. Condon Distinguished Professor of Chemistry and Biochemistry at the University of Colorado, Boulder, Carl Lineberger will deliver the Fall Eyring Lectures on November 8 and 9, 2012.

Professor Lineberger received his Ph.D. in 1965 from the Georgia Institute of Technology. He joined the University of Colorado faculty in 1970 where his is also a Fellow of JILA.

Lineberger's research centers on the application of lasers to problems in chemical physics, especially those involving gas phase anions. Particular interests include photoelectron and photodetachment spectroscopy, electron affinities, energetics and structure of transient species, dipole-bound states, metal diatoms and clusters, and ultrafast processes in molecular clusters.

Lineberger has been awarded Sloan, Dreyfus and Guggenheim Fellowships. He has been awarded the H. P. Broida Prize in Chemical Physics, given by the American Physical Society, the Bomem-Michelson Prize, the William F. Meggers Prize from the Optical Society of America, the Earl K. Plyler Prize from the American Physical Society.

The American Chemical Society has selected him for their Irving Langmuir Prize in Chemical Physics and the Peter Debye Award in Physical Chemistry.

Lineberger has been a member of the National Academy of Sciences since 1983 and the American Academy of Arts and Sciences since 1995. In 2011, he was nominated by President Obama for Membership on the National Science Board, and subsequently confirmed by the US Senate. He is a Member of the Executive Committee of NSB.

more information on Eyring Lectures in Chemistry and Biochemistry

October 31, 2012
New research award drives development of nanoscale diagnostics, therapy

Scientific and medical research usually advances through the slow, painstaking accumulation of knowledge. Occasionally, however, radical ideas disrupt established patterns and may open up entirely new fields of study.

Hao Yan, a researcher at Arizona State University’s Biodesign Institute, is working in one such domain. Known as theranostics, (a contraction of ‘therapy’ and ‘diagnostics’), the research represents a fresh approach to the diagnosis and treatment of disease, relying on nano-scale agents fabricated to carry out a range of functions in the body.

Yan and his collaborator Milan N. Stojanovic of Columbia University’s Department of Medicine are recent recipients of the 2012 Transformative Research Grant, an award specifically developed by the National Institutes of Health (NIH) to nurture unconventional, paradigm-shifting investigations. Established in 2009, the program is open to exceptional individuals and teams of investigators who propose path-breaking research in their chosen area.

According to NIH director Francis S. Collins, the Common Fund high-risk, high-reward program “provides opportunities for innovative investigators in any area of health research to take risks when the potential impact in biomedical and behavioral science is high." The award is so selective that a mere 20 projects were chosen this year to receive it, out of over 700 applicants.

Professor Yan is a specialist in nanoscale architectural forms and a pioneer in the field of DNA origami, a technique that capitalizes on the base-pairing properties of DNA nucleotides to construct elaborate and useful structures, some no larger than a virus particle.

In earlier research, Yan demonstrated the ability of DNA building blocks to create nanostructures resembling tiny baskets and bowls, spirals, spheres and Mobius shapes and even a spider-like entity capable crawling over a nanoscale trackway, guided in its movements by molecular cues.

A brilliant investigator (and one of the youngest researchers in the country to hold an endowed academic chair), Yan has extended the DNA origami method in significant ways, applying imaging techniques including Atomic Force Microscopy (AFM) to reveal a Lilliputian world of 2-D and 3-D nanostructures, many mimicking forms found in nature.

Under the new NIH award, Yan and Stojanovic will develop a range of theranostic nano-objects suitable for eventual in vivo diagnosis and therapy. In a scenario reminiscent of the sci-fi classic Fantastic Voyage, these futuristic intelligent agents will be designed to swarm through the bloodstream, carrying out imaging, diagnostic and therapeutic functions.

The theranostic nano-objects may be used to detect molecular early warning signals of disease – known as biomarkers – and report their status to a researcher or physician. They may also perform corrective operations by releasing various therapeutic agents or carrying out search-and-destroy maneuvers against aberrant cells.

Numerous applications exist for theranostic nano-objects and include the autonomous control of glucose levels in diabetes, the prevention of irreversible shock in intensive care patients and the selective elimination of narrow subpopulations of cells, as in the targeting of malignancy or infection.

To reach this new frontier of personalized disease diagnosis and treatment, Yan, Stojanovic and their colleagues will first seek to establish the basic science foundations and engineering principles underlying the use of the compact autonomous molecular devices under study.

Initial efforts will focus on methods to control the behavior of “neggs” (nano-eggs), made of deoxyribonucleic acids. The structures will contain sensors, imaging and/or therapeutic moieties, and molecular computing functions. Neggs are dynamic forms, capable of locking or unlocking upon receiving signals from their surrounding environment – for example, they may be triggered by the presence or absence of one or more biomarkers.

In the course of the new research, Yan and Stojanovic will demonstrate the transformative potential of theranostic nano-objects by engineering increasingly complex behaviors for neggs and mapping these to proof-of-concept therapeutic prototypes for which no existing technologies are satisfactory.

Some examples include opening a negg if an analyte rises above (e.g., glucose) or drops below (e.g., vasopressin) its “normal” concentration; marking for elimination/imaging narrow subpopulations of cells based on multiple surface markers, while protecting cells that differ in a single marker (e.g., on lymphocytes); and demonstrating amplification of MRI contrast agents on a targeted cell type (for example, ?-cells).

The new area of theranostics likely holds many surprises. Rapid developments in biology, chemistry, pharmacology, nanotechnology, imaging and medicine will expand the scope of research and eventually multiply the useful applications of this powerful approach. Theranostic systems may soon play a commanding role in the accurate monitoring of drug delivery, release and efficacy and for the pre-screening of patients for a range personalized medical interventions.

“We hope our interdisciplinary approach will lead to important new directions in theranostic applications,” Yan says. “This is a 5-year project and we need to work very hard now toward this goal.”

In addition to his appointment at the Biodesign Institute, Yan is a professor in the department of Chemistry and Biochemistry in the College of Liberal Arts and Sciences at ASU.

He holds the inaugural Milton D. Glick Distinguished Chair of Chemistry and Biochemistry.

Richard Harth, Richard.Harth@asu.edu
The Biodesign Institute

This illustration by the Mayo Clinic is an example of abnormal bone density in osteoporosis. Image by permission of Mayo Foundation for Medical Education and Research. All rights reserved. Ariel Anbar, a professor in ASU's Department of Chemistry and Biochemistry and the School of Earth and Space Exploration, and senior author of the study in his lab at ASU. Ariel Anbar, a professor in ASU’s Department of Chemistry and Biochemistry and the School of Earth and Space Exploration, and senior author of the study in his lab at ASU.

Oct 24, 2012
A new technique for detecting bone loss

Airing for the first time last night on KAET's "ASU Discovers," the work of scientists at ASU including Ariel Anbar, a professor in ASU’s Department of Chemistry and Biochemistry and the School of Earth and Space Exploration and NASA's Scott M. Smith, NASA nutritionist was highlighted.

These researchers have taken on the medical challenge of early detection of bone loss by developing and applying a technique that originated in the Earth sciences. In a new study, this technique was more sensitive in detecting bone loss than the X-ray method used today, with less risk to patients. Eventually, it may find use in clinical settings, and could pave the way for additional innovative biosignatures to detect disease.

“Osteoporosis, a disease in which bones grow weaker, threatens more than half of Americans over age 50,” explained Anbar who is also from ASU's College of Liberal Arts and Sciences.

“NASA conducts these studies because astronauts in microgravity experience skeletal unloading and suffer bone loss,” said Smith. “It’s one of the major problems in human spaceflight, and we need to find better ways to monitor and counteract it. But the methods used to detect the effects of skeletal unloading in astronauts are also relevant to general medicine.”

With the new technique, bone loss is detected by carefully analyzing the isotopes of the chemical element calcium that are naturally present in urine. Isotopes are atoms of an element that differ in their masses. Patients do not need to ingest any artificial tracers and are not exposed to any radiation, so there is virtually no risk.

Bone formation favors lighter calcium isotopes and picks them over the heavier ones. Other factors, especially bone destruction, also come into play, making the human body quite complicated.

But 15 years ago, Joseph Skulan, now an adjunct professor at ASU, combined all the factors into a mathematical model that predicted that calcium isotope ratios in blood and urine should be extremely sensitive to bone mineral balance.

“Bone is continuously being formed and destroyed,” Skulan explained. “In healthy, active humans, these processes are in balance. But if a disease throws the balance off then you ought to see a shift in the calcium isotope ratios.”

Rafael Fonseca, chair of the Department of Medicine at the Mayo Clinic in Arizona, and a specialist in the bone-destroying disease multiple myeloma is partnering with the ASU team on further bone loss research.

“Right now, pain is usually the first indication that cancer is affecting bones. If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care,” Fonseca said.

Article source:
KAET - Channel 8 "ASU Discovers"

Article:
http://www.azpbs.org/asu/asu_discovers/
Editor's Note: Links are included for informational purposes only. Due to varying editorial policies, news publications may remove or change a link for archival purposes at any time without notice.

Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

October 9, 2012
Water-hating knife slices droplet in half

To quote Jacob Aron reporting for the New Scientist blog, “Cutting a drop of water in half may sound like the kind of impossible task given to heroes of folk tales. You don't need a magic knife, though – just one that really, really hates liquid (water).”

Recently published work led by graduate student Ryan Yanashima and associate professor Mark Hayes in the Department of Chemistry and Biochemistry in ASU’s College of Liberal Arts and Sciences, and initiated by professor Antonio Garcia in ASU’s School of Biological and Health Systems Engineering, has shown that a superhydrophobic knife can create two cleanly separated drops of water, with potential applications in biomedical research.

Watch how a drop of water can be separated in this youtube video http://www.youtube.com/watch?v=a0tnfeK1NY4&feature=youtu.be

By creating two droplets from a single drop under very controlled conditions, a variety of micro and nano techniques can be used to study the contents of the drop or produce very small amounts of a rare molecule or biological structure. For example, in biomedicine there can be reason to isolate a single, rare cell (such as a cell suspected of being cancerous) and perform a series of analyses to detect what exactly is in the cell that makes it different from others.

“Isoelectric focusing is a means of separating and concentrating proteins in a sample, and we are able to show this could be done on the scale of, and within, a single water droplet," explains Yanashima. "Our work on drop splitting is a follow-up to show how one could reliably split the sample droplet so that we don't have undesired mixing within the droplet, which would preserve the separated contents (proteins, as an example) contained within.”

“Scientists in general have been trying to understand cells and the details of how they function down to the molecular level, and they have also been working on ways to separate every molecule in a liquid," says Garcia. "We hope that our work stimulates more creative ideas on how to achieve these goals and perhaps create new technologies that we cannot yet imagine.”

“Our work points to fundamental physical advances being interesting and popular, yet practically applicable to biotechnology problems of immediate impact,” explains Hayes.

Article source:
New Scientist

Article:
http://www.newscientist.com/blogs/shortsharpscience/2012/09/water-hating-knife-cuts-drops.html
Editor's Note: Links are included for informational purposes only. Due to varying editorial policies, news publications may remove or change a link for archival purposes at any time without notice.

Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

October 2, 2012
Faculty appointment in chemistry and biochemistry for new executive director of Biodesign Institute

Raymond DuBois, an internationally renowned physician-scientist whose research has advanced the understanding of the molecular basis for the prevention of colon cancer, has been named executive director of Arizona State University’s Biodesign Institute.

He also will hold the Dalton Chair in ASU’s College of Health Solutions with joint appointments in chemistry and biochemistry. In addition, he will have a joint appointment with Mayo Clinic, co-leading the cancer prevention program.

DuBois, whose position will be effective Dec. 1, 2012, comes to ASU from The University of Texas MD Anderson Cancer Center in Houston, where he served as provost and executive vice president, and professor of cancer biology and cancer medicine. At MD Anderson he was responsible for developing and overseeing research strategy, faculty, the School of Health Professions, graduate education programs and initiatives, and Global Academic Programs.

ASU’s Biodesign Institute is a unique interdisciplinary research endeavor devoted to bio-inspired innovation – that is, using nature’s building principles as a guideline for addressing a range of problems and challenges in health care, sustainability and security. With 10 research centers in 350,000 square feet of LEED certified laboratories, 700 employees and 208 active research projects, the Biodesign Institute is a nerve center for biomedical, sustainability and national security discovery.

“The Biodesign Institute was established 10 years ago with the intention of it becoming a world-class research enterprise. It has achieved that status,” says ASU President Michael M. Crow. “Now it’s time to put the rocket boosters on and advance to what I call Biodesign 2.0.

"In Ray DuBois we have not only an extraordinary researcher, but also someone gifted in research administration. We are fortunate to have such an accomplished scientist and visionary lead Biodesign into its next phase of development.”

“I have spent my professional career in academic medicine and I am delighted to be given the opportunity to head up Biodesign at ASU and venture into some very exciting areas that are crucial to the future of the planet,” DuBois said. “The institute was founded on a remarkably innovative concept – one that offers flexibility and cross-discipline collaborations that have the potential to positively impact mankind in incalculable ways. I can’t wait to get started. I believe that leading the Biodesign Institute is not only going to be intellectually stimulating and personally rewarding, but also a lot of fun.”

“Dr. Dubois’ broad depth of expertise in cancer prevention and cancer translational research will be a tremendous asset to Mayo Clinic and Arizona State University’s collaborative cancer fighting efforts," said Wyatt W. Decker, vice president of Mayo Clinic and CEO of Mayo Clinic in Arizona. "We look forward to having Dr. Dubois an integral part of our team as we continue to expand the Mayo Clinic Cancer Center presence in the Southwest.”

“The recruitment of Dr. DuBois to lead the Biodesign Institute is a tremendous positive for ASU,” said Jeffrey M. Trent, TGen’s president and research director. “Further, there is no question in my mind that Ray’s clinical insights, research, demeanor, integrity and focus on academic excellence should help galvanize Arizona’s biomedical community around key questions that can benefit cancer patients. His own research efforts have profoundly impacted the field of cancer prevention, leading to the development of even more effective strategies to both treat and prevent cancer.

“Ray is an internationally recognized physician-scientist, and having had the privilege of interacting with him for more than two decades, I can state with assurance that he will provide exceptional leadership to help position the Biodesign Institute into the future,” Trent said.

DuBois came to MD Anderson from Vanderbilt University Medical Center in Nashville, Tenn., where he was director of the Vanderbilt-Ingram Cancer Center, the B.F. Byrd Jr. Professor of Medical Oncology and professor of medicine, cell biology and cancer biology.

The author of more than 135 peer reviewed publications, DuBois began his academic research career in 1991 as an assistant professor at Vanderbilt. He had received a bachelor's in biochemistry from Texas A&M University (1977), a doctorate in biochemistry from The University of Texas Southwestern Medical Center in Dallas (1981) and a medical degree from The University of Texas Health Science Center in San Antonio (1985). From 1985 to 1991, he completed his postgraduate training at the Johns Hopkins Hospital as an intern and resident on the Osler medical service, followed by a fellowship in gastroenterology and postdoctoral research fellowship with Nobel Laureate Daniel Nathans.

After joining the faculty at Vanderbilt, DuBois was promoted to full professor in six years, his research having advanced the understanding of colorectal cancer and having led to the development of promising cancer prevention and treatment strategies.

In the 1990s, DuBois and colleagues reported that colorectal tumors contained high levels of the enzyme cyclo-oxygenase-2 (COX-2). This enzyme is a key step in the production of pro-inflammatory mediators such as prostaglandin E2 (PGE2). The DuBois team was the first to show that colorectal cancers over-expressed COX-2 and their research defined a series of critical molecular pathways involved in COX-2 expression – namely, that blocking or inhibiting the COX-2 enzyme would cause colorectal tumors to shrink. This work led to clinical trials and the treatment of precancerous polyps with Celebrex, an arthritis drug that selectively inhibits COX-2.

DuBois explains, “What’s interesting about my research as it relates to biodesign is that it has been known for centuries that the bark of the willow tree was used to treat pain and inflammation. By the 19th century an extract from willow bark was found to contain an active ingredient, salicylic acid, which was the chemical building block used to make aspirin. Aspirin was the first medicine marketed that inhibited cyclo-oxygenase, laying the groundwork for the discovery of the next generation of inhibitors like Celebrex that are available today for treating symptoms of pain and inflammation associated with arthritis. In other words, using a compound derived from the bark of the willow tree as a starting point, a whole new class of agents has been developed that not only reduces pain, but also inhibits the development of colorectal cancer.”

From 1998 to 2004, DuBois directed Vanderbilt’s Division of Gastroenterology, Hepatology and Nutrition. During his tenure, he earned a reputation for outstanding leadership, marked by substantial growth in faculty, and the division’s research funding and clinical revenues more than doubled. He was also awarded such major grants as a National Cancer Institute (NCI) Program Project grant for the discovery of novel cancer prevention targets and a National Institutes of Health Digestive Disease Research Center grant, one of only 16 in the country. He currently is the principal investigator on the only prevention program project grant awarded by the NCI in 2012.

Among his many awards and honors are: the Ellen F. Knisely Distinguished Chair in Colon Cancer Research; Johns Hopkins Society of Scholars; Anthony Dipple Carcinogenesis Award from Oxford University Press; Distinguished Achievement Award from the American Gastroenterological Association; Dorothy P. Landon Cancer Research Prize; Richard and Hinda Rosenthal Foundation Cancer Research Award; E.V. Newman Research Prize from the Vanderbilt University Department of Medicine; Outstanding Investigator Award from the American Federation for Medical Research; and Catedra Gonzalo Rio Arronte Award from Mexico City, Mexico.

He is a Fellow of the American Association for the Advancement of Science, is a past president of the American Association for Cancer Research and serves on the executive committee of the Aspen Cancer Conference. In addition, he is a founding scientific advisor for both the National Colon Cancer Research Alliance and Stand Up To Cancer.

Ray’s wife, Lisa A. DuBois, is a distinguished journalist and author. They have two children, a daughter, Shelley, and a son, Ethan.

September 24, 2012
ASU fetes Hao Yan as inaugural Glick Chair

The Milton Glick Distinguished Chair. ASU President Michael Crow, Peggy Glick, assistant professor Yan Liu and professor Han Yan (l-r), celebrate Hao Yan's honor of being named the inaugural Milton "Milt" Glick Distinguished Chair in Chemistry and Biochemistry.

Passing the Hat. Milt Glick could always be seen strolling around ASU's campus with a stylish fedora during his 15-year tenure as senior vice president, provost and executive vice president. Peggy Glick and President Crow look on approvingly as Hao Yan dons one of Milt's favorites.

In a celebration before a packed house at the Biodesign Institute, Arizona State University professor Hao Yan was honored as the inaugural Milton D. Glick Distinguished Chair of Chemistry and Biochemistry.

The award is named for chemistry professor Milton “Milt” Glick who passed away last year. Glick came to ASU in the early 1990s and served for 15 years--first as senior vice president and then as ASU’s chief academic officer as provost and executive vice president before assuming the presidency of the University of Nevada Reno from 2006 until his death.

“Milt was one of America’s great educators, and helped ASU become a great university through his 15 years of leadership, intellect and drive," said Crow. “Since Milt started out his career as a chemistry professor, we wanted to honor one of the very brightest chemistry faculty stars here at ASU, Professor Hao Yan.”

Yan is a recognized leader in the fast-moving field known as structural DNA nanotechnology, or DNA origami, that self-assembles DNA into a broad range of technological applications important for human health and bio-electronic sensing devices. Yan’s inspiration to his lab, students and break-neck speed of developing new technologies may spark a ‘bottom up’ nanotechnology industry to developing new solutions in medicine, energy and electronics.

“I am very honored and humbled to be the recipient of this great honor by the Glick family and President Crow,” said Yan. "I’d also like to give a special thanks to Stuart Lindsay, the director of Biodesign’s Center for Single Molecule Biophysics, who was instrumental in originally recruiting me to ASU, with its vision of performing science in service to society and solving grand challenges. This is truly a memorable moment for me, my family and my lab.”

In addition to his research team’s scientific achievements that have braced the covers of leading research journals such as Science and Nature, Yan is just as dedicated in the classroom. As a professor in the department of chemistry and biochemistry in the College of Liberal Arts and Sciences, Yan has created an interactive environment in undergraduate and graduate courses that allows students to participate in class discussions, developed graduate courses that integrate research advances in cutting-edge interdisciplinary classes, and mentored and inspired students to be original thinkers in both research and the classroom.

Joining the celebration were well-wishers from across ASU and members of the Glick family, including widow Peggy Glick.

A Great Educator. President Crow reminisced about Milt Glick's guidance and leadership in helping shape ASU's dramatic expansion and growing reputation as a leading research university.	The Chemist, by ASU Regents Professor Alberto Rios. President Crow hands a commemorative photo of Milt Glick to Peggy Glick, that features s a special poem written by long time friend and Regents Professor Alberto Rios (far right)

“I think Milt would be thrilled with this way of remembering him here,” said Glick. “He would be thrilled with associating him with the words ‘distinguished professor’.” He would be thrilled that, with this professorship, there is one more of those ‘franchise players’ that he used to talk about at every department meeting. And he would happy to know it happened at this university, where he was the provost for so long, and where he really grow up as an academic administrator.”

A long time friend of Glick’s on the ASU faculty, Regents' professor and poet Alberto Rios, capped off the occasion with a special composition.

ASU cloud water collector installed on the peak of Whistler Mountain in Canada (summer 2010). Photo by: Pierre Herckes

Two ASU students preparing a cloud water collector on Whistler Mountain in Canada. Photo by: Pierre Herckes

Two ASU students performing maintenance on a cloud water collector on Mt. Elden (Arizona). Photo by: Pierre Herckes

September 19, 2012
Chemistry professor's cloud research receives national attention

To quote Marlene Cimons reporting for the National Science Foundation, "When Pierre Herckes goes to the top of a mountain, it's not for the view. In fact, the more clouds and fog, the better."

Pierre Herckes is an associate professor in the Department of Chemistry and Biochemistry in ASU's College of Liberal Arts and Sciences. He studies how cloud droplets act as miniscule chemical reactors that can transform atmospheric gases and particles into new and sometimes threatening chemical forms. This has a direct impact on atmospheric composition with implications for human health and global climate.

The health related aspect of Herckes's research stems from chemical reactions in clouds or fogs that might transform some relatively innocent chemicals into, for example, the potent carcinogen and mutagen, N-nitroso dimethylamine (NDMA). Herckes is tackling the problem through laboratory and observational field studies.

“We don’t completely understand the way particles are actually formed in the atmosphere,” explains Herckes. “This is a big problem for air quality and climate models since we know the effects of primary emissions in the atmosphere, but don’t understand well the importance of secondary particles, that is, these particles that are formed in the atmosphere from gases.”

“We are interested in the chemistry going on, and physically, which particles and gases get into cloud droplets and which don’t,” he says. “We want to better understand the particle/cloud interactions, which are some of the highest uncertainties in climate modeling. We know quite well what gases do. A substantial part of the uncertainties of climate are based on what the particles do, and how they interact with clouds. The particles can be warming, but they also can be cooling and impact the frequency and amount of precipitation."

Article source:
US News and World Report

Article:
http://www.usnews.com/science/articles/2012/09/19/chemistry-and-clouds

Editor's Note: Links are included for informational purposes only. Due to varying editorial policies, news publications may remove or change a link for archival purposes at any time without notice.

Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

September 17, 2012
Wade Van Horn, Science Foundation Arizona Early Career Scholar

The future of Arizona and the nation is linked to the creativity and competitiveness of the next generation of academic researchers in science and engineering. Recognizing this, SFAz initiated the Bisgrove Scholars program to attract and retain exceptional individuals who have demonstrated substantial achievement and possess the potential to transform ideas into great value for society.

Assistant Professor Wade Van Horn, recently recruited to ASU’s Department of Chemistry and Biochemistry, is a current SFAz Bisgrove Scholar.

Van Horn has come directly to ASU from a post-doctoral appointment at Vanderbilt University, where he studied the biology and biophysics of proteins in cell membranes. Professor Van Horn completed his graduate and undergraduate studies in chemistry at the University of Utah and Brigham Young University respectively.

Van Horn’s current research interests involve the study of the structure and function of membrane proteins. The most important processes in all living cells, such as respiration, photosynthesis, cell communications, cell import and export, cell growth and recognition take place with the help of membrane proteins. The proteins do not act on their own, but they communicate within cells by binding, releasing and transmitting signals to other proteins.

Over sixty percent of drug molecules target membrane proteins and hundreds of diseases involve a flaw in the way they are folded or assembled. Yet despite their importance and ubiquity, membrane proteins remain difficult to study and the scientific community still knows very little about their structure and how it affects their function. In fact, thus far, less than half a percent of known protein structures are membrane proteins, which means we still have much to learn about the roles they play in health and disease.

In order to increase our knowledge in this area and improve the way drugs are designed, Van Horn will visualize protein structure by studying the magnetic properties of the atoms they contain. These properties depend on the composition and arrangement of the molecules that these atoms form as well as their surroundings. The techniques he will use to study membrane proteins will complement others that are currently in use at ASU that rely on X-rays. His research program will have a synergistic effect on several initiatives at ASU, promising stimulus for writing highly collaborative grant proposals. It is expected that Van Horn will join the Membrane Proteins in Infectious Diseases Center funded by the National Institutes of Health and headed by Professor Petra Fromme, also from the department of chemistry and biochemistry. Van Horn will also become a member of the Virginia G. Piper Center for Personalized Medicine led by Professor Joshua Labaer Director of Personalized diagnostics at the Biodesign Institute and the department of chemistry and biochemistry.

Van Horn also has a strong background in teaching. He has been teaching since he was an undergraduate when he received the Garth L. Lee teaching award. At the time, he was also acting as manager of the Chemistry Department Lecture Demonstration Laboratory at Brigham Young University, and he used to arrange for chemical experiments to be demonstrated to K-12 children who attended schools that could not afford the equipment. Van Horn is currently preparing an application to the National Science Foundation that will include a framework for interfacing directly with low income K-12 students in the Phoenix area.

September 14, 2012
Pioneering anti-cancer chemist to receive highest honor

PULLMAN, Wash. - George R. Pettit, an organic chemist who pioneered the search for anti-cancer compounds in marine organisms as well as insects and plants, has been awarded Washington State University’s highest alumni honor, the Regents’ Distinguished Alumnus Award.

The 1952 graduate (B.S., chemistry) will be will be honored at 1:30 p.m. Thursday, Sept. 20, in the Compton Union Building (CUB) Auditorium at WSU Pullman, where he will deliver a free, public address, "From the Indian Ocean to Global Clinics: Discovering new paths to improve cancer treatment."

"Those who know of Bob Pettit consider him a pioneer, innovator and simply a giant in the field of cancer drug discovery,” says Cliff Berkman, a WSU organic chemist who also works on anti-cancer agents. "More than anyone, Bob successfully translated his early fascination with nature’s creations to a professional career devoted to discovering and developing new drugs to battle nature’s most grievous diseases.”

Defined the cutting edge of his field
Over six decades, Pettit, 83, has published more than a dozen books and about 800 peer-reviewed scientific articles while securing more than five dozen U.S. patents and several hundred foreign patents for anti-cancer compounds.

Writing for Pettit’s nomination, Michael Boyd, director of the Mitchell Cancer Institute at the University of Southern Alabama, said Pettit "is at, indeed has established and defined, the cutting edge of his field. There is no other individual in the world who can claim anywhere near a comparable number of new anticancer compounds discovered and placed into preclinical or clinical drug development.”

Early curiosity prompted investigations
Pettit’s fascination with potential natural cancer fighters dates to his days as a teenager on the New Jersey shore. He worked in a hospital pathology lab, where he first saw the ravages of cancer, while observing sea life in tide pools and noting that various creatures never seemed sick, let alone afflicted with cancer. Somewhere in those creatures, he reasoned, could be anti-cancer compounds evolved over millions of years.

After earning master’s and doctoral degrees at Wayne State University, Pettit launched systematic searches for anti-cancer substances in marine animals, plants and microorganisms, beginning with fungi when he was on the faculty at the University of Maine. Over a quarter-century, he and colleagues at Arizona State University, where he is a Regents’ Professor, collected more than 3,000 plant species, some 1,000 insect species and more than 14,000 marine species.

In lieu of vacations, he, his wife and five children collected specimens from Mexico to Alaska. One of his sons was his diving partner on expeditions to such places as Micronesia, the Coral Sea and the coast of Papua New Guinea.

Drugs in clinical trials for cancer, Alzheimer’s
A dozen drugs discovered by Pettit and his Arizona State colleagues are in phase 1 to phase 3 of human cancer clinical trials. One is also in trials in ophthalmology, another is in a trial against Alzheimer’s disease, and trials are planned for a drug to fight pregnancy preeclampsia.

One of Pettit’s early marine-based leads, bryostatin 1, has undergone nearly 100 trials. It ended up receiving FDA orphan drug approval for esophageal carcinoma in conjunction with Taxol.

Some discoveries have involved major innovation. Early clinical trials for dolastatin would have required some 700 tons of the source material, the mollusk sea hare. Pettit developed a process to synthesize the material so enough material could be developed for the trials.

Inspiring future generations
"There is no doubt that Bob Pettit’s career arc and achievements are truly phenomenal,” WSU’s Berkman says. "Now here at WSU, where his academic career began, we are fortunate to have the opportunity to both celebrate his remarkable accomplishments and share his story to inspire a future generation of scientists primed to tackle the most important issues facing human health.”

Since 1962, the Regents’ Distinguished Alumnus Award has honored individuals who have made significant contributions to society and, through their accomplishments, brought attention to the quality of a WSU education. Recipients have included U.S. ambassadors, doctors, educators, business leaders, scientists, journalists, athletes, authors and others.

Contact:
Eric Sorensen, WSU science writer, 509-335-4846, eric.sorensen@wsu.edu

August 31, 2012
Professor earns prestigious Early Career Award from Department of Energy

Anne Katherine Jones, an assistant professor in ASU’s Department of Chemistry and Biochemistry and the Center for Bioenergy and Photosynthesis, has recently earned a Department of Energy (DOE) Office of Science Early Career Award. This is a first for an Arizona university.

The DOE Early Career Research Program, now in its fourth year, supports the development of individual research programs of outstanding scientists early in their careers and stimulates research careers in the disciplines supported by the DOE Office of Science.

Jones’s research project will characterize a group of enzymes, biological catalysts, known as soluble [nickel iron]-hydrogenases.

“These protein catalysts are the lynchpins of biological hydrogen production by a wide range of different microorganisms. Studies of these enzymes may lead to improvements in bio-hydrogen production and utilization,” Jones explained.

"Microorganisms use and produce fuels by moving around electrons, electricity. They have found ways to couple the chemistry of producing fuels directly to electricity using catalysts based only on earth abundant, renewable materials. We would like to be able to either use these natural processes as blueprints to develop new bioenergetic pathways or to develop bio-inspired catalysts, but many basic questions regarding how these proteins work remain unanswered. This project utilizes electrochemical techniques to characterize the catalytic process at a molecular level and to start filling in details of how catalytic properties can be controlled and manipulated,” continued Jones.

Understanding the biochemistry and biophysics of catalysis by these systems at a molecular level is essential to exploiting such catalysts in military and civilian applications, for example, disease detection and prevention, industrial catalysis, and bio-inspired renewable energy generation.

“Anne Jones has extended a fine departmental tradition of winning such awards – several department members currently hold NSF CAREER awards, but this is the first from the DOE. It is one of the DOE’s premier funding competitions, and one that is directed toward young faculty members just starting their professional careers,” stated Daniel Buttry, chair of the department of chemistry and biochemistry in the College of Liberal Arts and Sciences.

Career awards provide a good example of the economic benefit that a research university can bring to its state. This award will provide $750,000 of research funding over the next five years. Each year, Arizona universities pour nearly $1 billion into the Arizona economy from their research activities, most of which are funded by the U.S. government and entities from outside the state. Research money brought in by universities is restricted money that can be used only for the research activity it supports.

Additional information about the DOE Early Career Research program including a complete list of fiscal year 2012 awardees can be found at http://science.energy.gov/early-career/.

Source:
Anne Jones, anne.katherine.jones@asu.edu
(480) 965-0356
Jenny Green, jenny.green@asu.edu
480-965-1430
Department of Chemistry and Biochemistry

August 22, 2012
Nanowell technology advances the study of proteins

Proteins are the biomolecules that carry out the business of biology. They provide structure to our cells and tissues including muscle, cartilage, ligaments, skin and hair. Proteins are also the machines of life, performing the molecular activities that keep us functioning including metabolizing energy, transmitting signals, attacking invaders, digesting food, dividing cells and overseeing innumerable other cellular processes. They are critical in the maintenance of health and when they malfunction they lead to disease.

Joshua LaBaer and his colleagues at Arizona State University’s Department of Chemistry and Biochemistry announce important improvements in protein microarray technology - a valuable tool for investigating the functions of the vast catalog of human proteins known as the proteome.

Protein microarrays are tools that display thousands of proteins in high spatial density. They allow investigators to probe the functions of thousands of proteins simultaneously. However, protein microarrays are usually arranged on a flat surface, like a microscope slide. This creates the possibility that reactants can diffuse from one reaction feature to the next.

The new nanotechnology platform uses etched nanowells that physically isolate each feature from all of the others, thereby preventing diffusion. This permits greater numbers of proteins to be analyzed at one time, at lower cost, and enables experiments that simply cannot be performed in a planar system. The improvements will be applied to the investigation of disease biomarkers—protein factors in blood that may be used to pinpoint diseases like cancer and diabetes while they are still in a pre-symptomatic state.

The group’s results recently appeared in the Journal of Proteome Research.

LaBaer’s approach addresses two fundamental challenges in protein microarray studies. The first has to do with the difficulties associated with the production, purification and storage of proteins. The second challenge (and central focus of this new work) is to improve the density of proteins that may be printed on a single microarray slide. The improved technique enhances the prospects for functional protein studies and is the highest density of individual proteins in nano-vessels demonstrated on a single slide.

“We envision broad applications for this platform, which enables running many simultaneous biochemical reactions without having to worry about local diffusion,” LaBaer says. “The piezoelectric printing can be used to address different reactants to the many different nanowells making the technology particularly powerful. That is, by mixing and matching, a researcher can execute many-to-many screening experiments or test various proteins to see if they act as subunits in complex biochemical reactions without having to worry about cross-reactivity or diffusion. ”

LaBaer directs the Virginia C. Piper Center for Personalized Diagnostics. The state-of-the-art facility at the Biodesign Institute is devoted to examining the subtleties of protein structure and function, particularly as they relate to the origin and progression of human diseases.

The center houses vast repositories of protein expression-ready plasmids from some 950 organisms, including humans. Plasmids are circular pieces of DNA that contain individual genes that code for various proteins – they act like little genetic flash drives that allow researchers to produce the proteins they carry. These plasmids are maintained in specialized robotic freezers at -80 degrees Celsius.

Through an international program for sharing genetic material—known as DNASU—more than 300,000 plasmid clones have been sent to laboratories in over 39 countries and 46 states. LaBaer’s group uses these tools to explore protein biomarkers for a variety of diseases including cancers of the breast, ovaries, prostate and lung.

Protein arrays typically consist of a glass slide or chip on which a library of proteins for study have been immobilized. High-throughput methods can then be applied to investigate protein behavior. But before proteins are suitable for microarray analyses, they typically must be purified—a messy and labor-intensive process. Purified proteins can degrade over time and have finicky requirements for storage and handling. These limitations encouraged LaBaer to approach the problem in a new way.

His efforts led to the development of the Nucleic Acid Programmable Protein Array (NAPPA). Rather than print purified proteins on the microarray slide, LaBaer instead prints the blueprints for these proteins, in the form of plasmid genes. A stable microarray can be prepared in this way and later coated with a specialized extract from cells that will convert the genes into proteins at the time of experiment.

The NAPPA technique has been used successfully for biomarker discovery studies, using planar slides each containing upwards of 2000 proteins. However, problems can arise at higher spot densities, due to diffusion. The higher the spot density in the microarray, the more serious the problem becomes.

An alternative method, outlined in the new study, is to replace planar slides with microarray slides meticulously etched with tiny nanowells, in which the selected biochemical reactants can be safely confined. The technique uses silicon micro fabrication technology to precisely etch thousands of nanowells onto slides. The group also developed a sophisticated liquid dispensing system to position and dispense genes and reagents into individual nanowells.

The higher density microarrays reduced the spatial separation of spotted proteins. Experiments with traditional planar slides showed that problems with diffusion of reactants occurred when center-to-center separation distances between spots on the microarray were less than 400nm. While minimal diffusion was observed at a spacing of 750nm, significant diffusion was noted when the spot separation was reduced to 375nm.

When the planar slides were replaced with a nanowell array, issues of diffusion and chemical cross-talk were largely eliminated. Each nanowell is sealable and therefore capable of fully isolating reaction events (protein expression and antibody capture) occurring simultaneously on the microarray. The etched nanowells, fabricated on silicon wafers, were each 75 microns deep and around 250 microns in diameter.

The extreme precision necessary to produce the high-density arrays required a new method of piezoelectric printing, allowing an array density of 8000 proteins per slide—the highest protein density thus far reported. For these experiments, 287 randomly selected genes, 193 from Vibrio cholera and 96 from human were used.

The team also produced proof-of-concept ultra high-density arrays containing 24,000 proteins per slide, again demonstrating largely diffusion-free results when the reactants were dispensed into the air-tight microchambers provided by the nanowells.

LaBaer says that the use of new ultra high-density protein microarrays introduces for the first time the possibility of proteome-wide screening. The addition of NAPPA eliminates issues of protein storage, purification and expression, making the combined technology an attractive, high-throughput avenue for accelerated protein research.

Written by: Richard Harth
Science Writer: Biodeisgn Institute

August 10, 2012
Pizzarello investigates Antarctic meteorites and cosmochemical evolution

Important new findings on the chemistry of ancient asteroid fragments known as Carbonaceous Chondrites have recently been reported. Scientists led by Sandra Pizzarello, a research professor within Arizona State University's Department of Chemistry and Biochemistry, have detected enantiomeric excesses of up to 60 percent of D-allo-isoleucine, a non-protein amino acid. At the time of publication, this fraction exceeded any previously published enantiomeric excesses. The findings offer important insights into the primitive distribution and evolution of organic compounds in the early Solar System and can help constrain models of the physical and chemical processes that were active in the accretionary disk of the nascent sun.
The work has recently been published in the Proceedings of the National Academy of Sciences (PNAS). The paper is titled, "Large enantiomeric excesses in primitive meteorites and the diverse effects of water in cosmochemical evolution", and is co-authored by Pizzarello, Devin L. Schrader, Adam A. Monroe, ASU chemistry graduate student, and Dante S. Lauretta.
One intriguing group of Carbonaceous Chondrites, the remarkably pristine Renazzo-type (CR) chondrites found in Antarctica, contain organic materials and water-soluble molecules such as amino acids and ammonia. Pizzarello et al. analyzed select CR meteorites with different petrographic classifications to assess the abundance and distribution of key organic compounds in the context of aqueous processes and concomitant hydrated mineral phases. According to the authors, several CR compounds such as amino acids and sugar alcohols are fully represented in rocks with no or minimal water exposure, indicating an origin for these compounds that may predate parent body processes.

Carbonaceous meteorites are known to contain organic materials as diverse as kerogen-like macromolecules and simpler soluble compounds. Because some meteoritic compounds are identical to biomolecules and may have molecular traits such as chiral asymmetry, meteorites give insights into the evolution of the biogenic elements ahead of biochemistry.
Several of these CR2 meteorites, provided by the ASU Center for Meteorite Studies and NASA’s Johnson Space Center, have been studied by Pizzarello and coworkers through the years. These studies have shown that the formation of meteoritic compounds span vast cosmic locales from the cold environments of the interstellar molecular clouds to various asteroidal bodies. One question debated by meteoriticists involves whether the water processes known to occur in some asteroids did foster the compounds’ final syntheses from precursors.
However, carbonaceous meteorites are also fragile and Earthlike rocks that, if not actually seen falling, easily go undetected and disappear into the environment. As a result, very few “meteorite falls” in storage exist. Pizzarello was able to obtain and study several carbonaceous meteorites found in Antarctica, where the mean subfreezing temperatures and very dry climate provide an excellent natural curatorial environment until the samples are collected.

"Large enantiomeric excesses in primitive meteorites and the diverse effects of water in cosmochemical evolution" Pizzarello S., Schrader D.L., Monroe A.A. and Lauretta D.S. PNAS www.pnas.org/cgi/doi/10.1073/pnas.1204865109 (2012).