New DNA nanoforms take shape

April 13, 2011

Miniature architectural forms – some no larger than viruses – have been constructed through a revolutionary technique known as DNA origami. Now, Hao Yan, Yan Liu and their colleagues at ASU’s Biodesign Institute have expanded the capability of this method to construct arbitrary, two- and three-dimensional shapes, mimicking those commonly found in nature.

Such diminutive forms may ultimately find their way into a wide array of devices, from ultra-tiny computing components to nanomedical sentries used to target and destroy aberrant cells or deliver therapeutics at the cellular or even molecular level. Download Full Image

In today’s issue of Science, the Yan group describes an approach that capitalizes on (and extends) the architectural potential of DNA. The new method is an important step in the direction of building nanoscale structures with complex curvature – a feat that has eluded conventional DNA origami methods.

“We are interested in developing a strategy to reproduce nature’s complex shapes,” Yan said.

The technique of DNA origami was introduced in 2006 by computer scientist Paul W.K. Rothemund of Caltech. It relies on the self-assembling properties of DNA’s four complementary base pairs, which fasten together the strands of the molecule’s famous double-helix. When these nucleotides, labeled A, T, C and G, interact, they join to one another according to a simple formula – A always pairs with T and C with G.

Nanodesigners such as Yan treat the DNA molecule as a versatile construction material – one they hope to borrow from nature and adapt for new purposes.

In traditional DNA origami, a two-dimensional shape is first conceptualized and drawn. This polygonal outline is then filled in using short segments of double-stranded DNA, arranged in parallel. These segments may be likened to pixels – digital elements used to create words and images displayed on a computer screen.

Indeed, Rothemund and others were able to use pixel-like segments of DNA to compose a variety of elegant 2-D shapes, (stars, rhomboids, snowflake forms, smiley faces, simple words and even maps), as well as some rudimentary 3-D structures. Each of these relies on the simple rules of self-assembly guiding nucleotide base paring.

Once the desired shape has been framed by a length of single-stranded DNA, short DNA “staple strands” integrate the structure and act as the glue to hold the desired shape together. The nucleotide sequence of the scaffold strand is composed in such a way that it runs through every helix in the design, like a serpentine thread knitting together a patchwork of fabric. Further reinforcement is provided by the staple strands, which are also pre-designed to attach to desired regions of the finished structure, through base pairing.

“To make curved objects requires moving beyond the approximation of curvature by rectangular pixels," Yan said. "People in the field are interested in this problem. For example, William Shih’s group at Harvard Medical School recently used targeted insertion and deletion of base pairs in selected segments within a 3-D building block to induce the desired curvature. Nevertheless, it remains a daunting task to engineer subtle curvatures on a 3-D surface."

“Our goal is to develop design principles that will allow researchers to model arbitrary 3-D shapes with control over the degree of surface curvature. In an escape from a rigid lattice model, our versatile strategy begins by defining the desired surface features of a target object with the scaffold, followed by manipulation of DNA conformation and shaping of crossover networks to achieve the design,” Liu said.

To achive this idea, Yan’s graduate student Dongran Han began by making simple 2-D concentric ring structures, each ring formed from a DNA double helix. The concentric rings are bound together by means of strategically placed crossover points. These are regions where one of the strands in a given double helix switches to an adjacent ring, bridging the gap between concentric helices. Such crossovers help maintain the structure of concentric rings, preventing the DNA from extending.

Varying the number of nucleotides between crossover points and the placement of crossovers allows the designer to combine sharp and rounded elements in a single 2-D form, as may be seen in figure 1 a & b, (with accompanying images produced by atomic force microscopy, revealing the actual structures that formed through self-assembly). A variety of such 2-D designs, including an opened 9-layer ring and a three-pointed star, were produced.

The network of crossover points also can be designed in such a way as to produce combinations of in-plane and out-of-plane curvature, allowing for the design of curved 3D nanostructures. While this method shows considerable versatility, the range of curvature is still limited for standard B form DNA, which will not tolerate large deviations from its preferred configuration – 10.5 base pairs/turn. However, as Jeanette Nangreave, one of the paper’s co-authors, explains, “Hao recognized that if you could slightly over twist or under twist these helices, you could produce different bending angles.”

Combining the method of concentric helices with such non-B-form DNA (with 9-12 base pairs/turn), enabled the group to produce sophisticated forms, including spheres, hemispheres, ellipsoid shells and finally—as a tour de force of nanodesign – a round-bottomed nanoflask, which appears unmistakably in a series of startling transmission electron microscopy images (see figure 1, c-f )

“This is a good example of teamwork in which each member brings their unique skills to the project to make things happen," Nangreave says. The other authors include Suchetan Pal and Zhengtao Deng, who also made significant contributions in imaging the structures.

Yan hopes to further expand the range of nanoforms possible through the new technique. Eventually, this will require longer lengths of single-stranded DNA able to provide necessary scaffolding for larger, more elaborate structures. He credits his brilliant student (and the paper’s first author) Dongran Han with a remarkable ability to conceptualize 2-D and 3-D nanoforms and to navigate the often-perplexing details of their design. Ultimately however, more sophisticated nanoarchitectures will require computer-aided design programs – an area the team is actively pursuing.

The successful construction of closed, 3-D nanoforms, such as the sphere, has opened the door to many exciting possibilities for the technology, particularly in the biomedical realm. Nanospheres could be introduced into living cells for example, releasing their contents under the influence of endonucleases or other digestive components. Another strategy might use such spheres as nanoreactors – sites where chemicals or functional groups could be brought together to accelerate reactions or carry out other chemical manipulations.

Richard Harth, richard.harth">">
Biodesign Institute

Britt Lewis

Communications Specialist, ASU Library

Outstanding professors receive 2011 Faculty Achievement Awards

April 13, 2011

Nine outstanding ASU faculty members have been honored with 2011 Faculty Achievement Awards. Seven have been recognized for their defining edge research and creative activities, and two for their excellence in classroom performance.

The nine individuals, representing a wide range of disciplines, were honored at a reception April 13 at the ASU Art Museum. The awards were presented by President Michael Crow, with an introduction by Elizabeth D. Capaldi, executive vice president and provost, and the deans. Download Full Image

The awards are made for a specific contribution appearing in the last 10 years that meets the highest standards of the discipline or profession. The contributions significantly change their professions in research, creative activities and undergraduate instruction, placing the achievements among the highest at the university.

After receiving input from the faculty, nominations for the Faculty Achievement Awards are made by deans and reviewed by panels of Regents’ and President’s Professors.

This is the fifth year for the annual awards.

This year’s awardees are the following:

• Defining Edge Research in Natural Sciences and Math: Gro V. Amdam, School of Life Sciences; and Martha R. McCartney, physics.

• Defining Edge Research in Humanities and Literary Work: Claudia Sadowski-Smith, English.

• Defining Edge Research in Social Science: Curtis W. Marean, School of Human Evolution and Social Change.

• Young Investigator: Eli P. Fenichel, School of Life Sciences.

• Innovation: Sidney Hecht, chemistry and biochemistry.

• Best Performance or Art Work: Melissa Pritchard, English.

• Excellence in Undergraduate Instruction: Amber Wutich, School of Human Evolution and Social Change.

• Excellence in Undergraduate Student Mentoring: Peter Jurutka, Division of Mathematical and Natural Sciences

Gro Amdam, associate professor in the School of Life Sciences

Amdam runs highly productive laboratories at both ASU and at the Norwegian University of Life Sciences. She has risen to the top of experts internationally in studies using the honey bee as a model for aging, behavior, nutrition and social networks.

Amdam looks at how social behavior evolves, and how the evolution of this complex behavior can influence other life-history traits, particularly aging. The creative nature of her studies and her brilliant intellect have attracted millions of research dollars, and her work has led to exploration of other public health challenges, including obesity.

She has been featured in Science magazine, has published in a wide range of top journals, and also has mentored 24 graduate and postdoctoral fellows since 2006.

“From bees to obesity, Amdam is a star at ASU, an entrepreneurial thinker who deserves broad recognition for her incendiary scientific insight and impactful approach to questions of human health and also creating understanding of a critical economic species,” says Robert E. Page, dean of the School of Life Sciences.

Martha R. McCartney, professor of physics

McCartney is one of three leading scientists in the world who use electron holography techniques to measure the electromagnetic properties of materials with nanoscale precision. She has significantly advanced the technique of electron holography, applying the technique to a wide range of contemporary materials.

McCartney is a prolific scientist who, over the past decade, has authored or co-authored nine invited book chapters and 67 publications in prominent international journals. During the same period she has given 32 invited lectures at conferences in 12 countries, as well as presenting another 20 invited seminars and colloquia.

“Evidence of the impact of her work is seen in the number of times her publications have been cited, 2,380 times“ says Sid Bacon, dean of natural sciences. “It is especially rewarding to note that Professor McCartney ‘is one of our own’ in that she received her Ph.D. from ASU in 1989 and has since spent her career at ASU.”

Claudia Sadowski-Smith, associate professor of English

Sadowski-Smith looks at issues of immigration, globalization and political action in her work. Her most recent book, “Border Fictions: Culture, Capital and Citizenship at U.S. Borders,” makes an original contribution by focusing on both the Mexican and Canadian borders, examining novels, short stories, plays and memoirs.

She has brought a highly sophisticated understanding of local complexities to the topic of borders, and has established a model that will encourage further comparative projects.

Supplementing this groundbreaking work, Sadowski-Smith has edited an acclaimed collection of essays, “Globalization on the Line,” that gained critical attention for bringing together a group of writers from diverse backgrounds and disciplines. Her work has been published in top journals and has been widely cited.

“With a book, a collection of essays and over 17 articles, Professor Sadowski-Smith has made an important impact in the discipline,” says Neal A. Lester, dean of humanities. ”The many important citations to her work across the country and beyond, as well as the many uses of her publications in undergraduate and graduate classrooms, further evidence the impact of this important work at all levels.”

Curtis Marean, professor in the School of Human Evolution and Social Change

Marean leads a multinational research team whose work in southern Africa has led to the discovery of critical scientific insights into how humans over 100,000 years ago coped with harsh environmental conditions during a time when humanity was in danger of extinction.

His dedication and cutting-edge research methods have resulted in new and fascinating discoveries in the social and natural sciences and have propelled him and ASU to the forefront of the field of anthropology and human origins.

Marean’s work was featured as a cover story in Scientific American, detailed in a special issue of the Journal of Human Evolution, and prompted an invitation to present at a Nobel conference. It also attracted a $2.5 million grant from the National Science Foundation, the largest NSF award ever given in archaeological research.

“Dr. Marean’s extraordinary discoveries, his leadership of a transdisciplinary research team and his articulation of that research into a synthetic theory exemplify an unmatched prowess in social science research at ASU and beyond,” says Alexandra Brewis Slade, executive director of the school.

Eli Fenichel, assistant professor in the School of Life Sciences

Fenichel is an emerging leader in bioeconomics, a field that emphasizes the importance of feedback between ecological systems and forward-thinking economic decisions.

He studies emerging infectious disease in wildlife, livestock and humans; invasive species impacts on fisheries and citrus production; and management of recreational fisheries. He has identified the role of human behavior in shaping ecological tipping points, and he also has shown that human behavioral response to disease risk can have a strong influence on the nature of a disease outbreak.

“Dr. Fenichel’s research is creative and use-inspired,” says Robert Page, dean of the School of Life Sciences. “His work partnering ecological systems and forward-looking decision makers and economists advances multiple disciplines simultaneously. He exemplifies the type of broad thinking, bridge-building researcher that we wish to cultivate here at ASU.”

Sidney Hecht, chemistry professor and director of the Center for BioEnergetics in the Biodesign Institute

Hecht is a leader in drug design and development, and his current work has the potential of alleviating the suffering of people with mitochondrial dysfunction.

People with this rare group of diseases number only in the tens of thousands worldwide, but their conditions are often debilitating and progressive. Currently patients with these afflictions are treated with huge doses of vitamins and antioxidants, but with little beneficial effect. One of the drugs Hecht developed for these diseases has recently completed Phase II clinical trials, and he is doing work on other products such as an antitumor agent.

“The drugs he currently has under development represent great strides in providing relief to patients,” says Edward Skibo, professor of chemistry. “Professor Hecht is innovative and highly productive, with 394 published papers and 19 patents. He also has received numerous honors for his work, including an Alfred P. Sloan Fellowship and a John Simon Guggenheim Fellowship.”

Melissa Pritchard, professor of creative writing in the English Department

Pritchard is an accomplished teacher and author of fiction who has moved into the world of creative nonfiction, writing about and teaching the victims and survivors of sexual trafficking in India.

In December 2006 she flew to Calcutta to teach a poetry workshop for girls rescued from sex trafficking. She returned to Calcutta and Delhi with ASU students in 2007 and 2009 to teach art and poetry workshops to child survivors.

In 2008 she traveled to a military hospital in Ecuador to interview female doctors and nurses, which inspired her to start a creative writing outreach program at Phoenix Children’s Hospital with ASU students. A year later she was an embedded war reporter in Afghanistan, an experience that led to a number of articles.

She is now a board member for The Afghan Women’s Writing Project, an award-winning online project linking American and Afghan women writers. The project’s first collegiate staged reading will take place at ASU on May 3. Meanwhile Pritchard’s fourth collection of short stories will be published next January, adding to a body of work that includes three novels and a biography.

“Her writing seems to come from a place that nourishes her spirit as a humanitarian,” says Neal Lester, dean of humanities. “Professor Pritchard engages her students in virtually all aspects of her writing projects and travels, which broadens the impact of her work. This evolution of her person and her craft has given her and this institution a different kind of global visibility.”

Amber Wutich, assistant professor of anthropology in the School of Human Evolution and Social Change

Wutich has developed an extraordinary reputation for teaching students. In addition to establishing a reputation as an excellent classroom teacher, she has significantly enhanced online instruction by creating challenging courses requiring high levels of instruction, engagement and study.

Students frequently mention her enthusiasm and passion for her subject, her high expectations, and how challenging her courses can be. She is known as an engaged and caring mentor who treats her students as emerging scholars, involving them in a range of important studies.

“The enthusiasm Dr. Wutich demonstrates in her teaching and the supportive yet disciplined environment she has created in the classroom are exceptional,” says Linda Lederman, dean of social sciences. “She also is the creator and co-director of the Global Ethnohydrology Study, a major research project which has expanded into a multi-year, multi-national study involving approximately 100 students.”

Peter Jurutka, associate professor in the division of mathematical and natural sciences

Jurutka has leveraged his exceptionally productive research program to teach students the craft of scientific research and to empower them to achieve their goals. He is a highly sought-after mentor, with more than 200 requests from students to gain research experience in his lab.

When Jurutka selects a student for inclusion in his research program, he looks for students who might not otherwise have a similar opportunity. Starting with little experience or self-confidence, they often go on to win awards and scholarships. Nearly all of the 32 students who have worked in his laboratory at ASU, many of them minority students, have pursued employment or entry into professional programs in health-related fields.

“Dr. Jurutka’s mentoring skills have transformed the lives of his students,” says Elizabeth Langland, dean of the New College of Interdisciplinary Arts and Sciences. “They have gone on to positions at the Translational Genomics Research Institute and the UA College of Medicine. Another is pursuing his MD at Stanford. Dr. Jurutka’s experiences and successes in mentoring represent an ideal that all ASU faculty strive to achieve.”

All of the award winners are in the College of Liberal Arts and Sciences except for Jurutka, who is in the New College of Interdisciplinary Arts and Sciences.