New award accelerates ASU's efforts in synthetic biology

October 13, 2014

A new four-year, multi-million dollar award from the Defense Advanced Research Projects Agency (DARPA) will be used to develop the technology necessary to synthesize, screen and sequence artificial genetic polymers composed of threose nucleic acid (TNA).

John Chaput, a professor in the Department of Chemistry and Biochemistry and research investigator in the Biodesign Institute will lead ASU’s effort to evolve TNA molecules that fold into novel 3-D shapes with ligand binding affinity and catalytic activity. John Chaput Download Full Image

Chaput is joined by ASU colleague Wade Van Horn, Department of Chemistry and Biochemistry, as well as Martin Egli, Department of Biochemistry at Vanderbilt University, and Jennifer Heemstra, Department of Chemistry, University of Utah.

The research is part of a new DARPA program called Folded Non-Natural Polymers with Biological Function (Fold F(x)), which plans to use synthetic polymers to address rapidly emerging health and defense threats.

Naturally occurring biopolymers like DNA, RNA and proteins are limited to functions that are required to sustain life, and prone to degradation by metabolic pathways that recycle biomolecules for other purposes. Recognizing these limitations, researchers would like to design new types of synthetic polymers, with versatile functions and folding motifs, that are stable to biological and harsh environmental conditions.

“This project integrates chemistry with molecular biology and genetics to produce synthetic molecules with tailor-made activities,” Chaput says.

The group's project is based on Chaput’s efforts to develop TNA as an artificial genetic polymer that is capable of heredity and evolution. This requires using organic chemistry to synthesize TNA monomers that are not commercially available, and engineering DNA polymerases to copy genetic information back and forth between TNA and DNA.

By introducing a selective amplification step into the replication cycle, like the ability to bind a small molecule target or catalyze a chemical reaction, large combinatorial pools can be searched for TNA molecules with desired functional properties.

This process is analogous to natural selection, where deleterious traits are removed from the population through iterative rounds of selection and amplification. In the case of TNA, molecules that meet the selective challenge will be recovered and amplified to generate progeny molecules that increase in abundance.

Affinity reagents, like those under development, may prove invaluable for biomedical applications. Their strength lies in their foreignness. Most diagnostic tests currently use antibodies as the affinity reagent. However, antibodies are not stable to heating, and can be degraded by enzymes present in biological samples.

In contrast, TNA affinity reagents are expected to remain functional after heating and cooling, and biological systems have not developed the kinds of enzymes necessary to recognize and degrade these synthetic polymers. A key aspect of the project is new technology that will quickly generate affinity reagents capable of converting the presence of a specific molecule into an optical signal. Heemstra says, “Directly selecting for TNA affinity reagents that have the desired optical output will enable us to rapidly respond to emerging threats.”

The team plans to determine the 3-D structure of functional TNA molecules isolated by in vitro selection. Egli will head the X-ray crystallography experiments and Van Horn the nuclear magnetic resonance spectroscopy efforts. Understanding the structural architecture of TNA is an important part of the overall project because very little is known about the atomic organization of TNA. Structural information gained from these studies will allow scientists to understand how unnatural polymers, like TNA, fold into globular structures.

“Since TNA has a different backbone than DNA and RNA, it will be interesting to learn what shapes these molecules can adopt. This structural information will help us to understand how TNA molecules perform more complex functions as biosensors and catalysts,” Van Horn says.

The new project will also introduce modified bases into TNA molecules. The combination of altered bases and threose backbone may yield novel folding geometries, with as-yet unknown functional properties, potentially allowing nucleotides to perform in a manner similar to proteins.

The technical challenges involved in the current project are formidable, and therefore consistent with the high-risk, high-reward model of DARPA-funded research. The team hopes the synthetic biology initiative will be a springboard for new ideas and techniques to be exploited by other labs and, in time, brought to the forefront of molecular biology.

The Department of Chemistry and Biochemistry is an academic unit in ASU's College of Liberal Arts and Sciences.

Richard Harth

Science writer, Biodesign Institute at ASU


ASU Cronkite School awards New York Times for disability reporting

October 13, 2014

A New York Times story about a group of men with intellectual disabilities who worked in servitude for decades has won top honors in the 2014 Katherine Schneider Journalism Award for Excellence in Reporting on Disability.

The second-place award went to the Anchorage Daily News. Judges also awarded an honorable mention to the Kansas City Star, as well as to a student-created deaf and hearing newscast at Arizona State University. Dan Barry Download Full Image

The contest, the only one devoted exclusively to disability reporting, is administered by the National Center on Disability and Journalism (NCDJ) at the Walter Cronkite School of Journalism and Mass Communication at Arizona State University. It was created in 2013 under a grant from Schneider, a retired clinical psychologist who has been blind since birth and who also supports the national Schneider Family Book Awards.

First place went to Dan Barry, Kassie Bracken and Nicole Bengiveno of The New York Times for “The ‘Boys’ in the Bunkhouse,” which describes in text, photos and video the lives of men who for 30 years worked in an Iowa turkey processing plant for almost no pay. The story raised questions about the federal law that permitted the men to be underpaid for doing the same work as their non-disabled colleagues, explained how regulators effectively sanctioned the exploitation, and detailed the squalid living conditions and mistreatment the men endured.

The New York Times team spent most of 2013 documenting the men’s experience, which was first revealed in stories in The Des Moines Register in 2009. Barry wrote and reported the winning story, utilizing court records and company documents and conducting the first interviews with the men. Bracken produced a half-hour documentary that accompanied the project, and Bengiveno was the lead photographer.

Other New York Times’ staff members who contributed to the project were Chuck Strum, deputy national editor; Meaghan Looram, deputy picture editor; John Woo, video editor; and Justine Simons, senior producer.

Barry will accept the award and a $5,000 cash prize on behalf of the Times’ team Nov. 3 at the Cronkite School, where he will also deliver a talk on his work to students, faculty and the public. The talk, part of the school’s Must See Mondays lecture series, will be held at 7 p.m. in the school’s First Amendment forum. It is free of charge and open to the public, and a sign language interpreter will be on hand.

Contest judges awarded second place to Kyle Hopkins and Marc Lester of the Anchorage Daily News for “State of Intoxication – Fetal Alcohol Spectrum Disorders.” The pair will share a $1,500 prize for the series, which provides an intimate portrait of children with Fetal Alcohol Spectrum Disorders. As common as autism, the disability is widely misunderstood and underdiagnosed in the U.S.

Eric Adler of The Kansas City Star was awarded honorable mention and $500 for “Denise’s Decision,” which chronicles the legal, medical and emotional ordeal of placing a loved one into long-term nursing care.

Finally, judges awarded special recognition and a $500 award to Peyton Gallovich and Melissa Yingst Huber of ASU for their startup enterprise, a television show that delivers the news for both deaf and hearing audiences. It is the first newscast to employ sign language, voices and captions to relay the news, allowing families to watch the news together. The bi-weekly show is available online and on stations in the Phoenix area.

Judges for the contest said they were impressed by the breadth and depth of the reporting on a range of disability issues but singled out Barry’s work for both the quality of the storytelling and the critical issues it unveiled.

Judge Jennifer LaFleur, senior editor for data journalism at the Center for Investigative Reporting, called the winning entry “a beautiful narrative that tells the horrific story of how the rights of more than two dozen disabled men were denied and how the system designed to protect them failed. ‘The ‘Boys’ in the Bunkhouse’ is an important contribution to disability journalism.”

Barry said, "We are humbled and honored by having been chosen as recipients of the 2014 Katherine Schneider Journalism Award for Excellence in Reporting on Disability. From the start we knew that the voices of the men of Atalissa needed to be heard, and we are just so fortunate that the men – and their many advocates – gave us their time and their stories. Thank you so much."

Judges reviewed 89 entries from journalists around the world. In addition to LaFleur, the judges were Jerry Ceppos, dean of the Manship School of Mass Communication at Louisiana State University and former vice president for news at Knight Ridder; Tony Coelho, former U.S. congressman and primary author and sponsor of the Americans with Disabilities Act;. Jennifer Longdon, a disability rights advocate and former chair of the Phoenix Mayor’s Commission on Disability Issues; and Tim McGuire, the Frank Russell Chair for the Business of Journalism at the Cronkite School and former editor and senior vice president of the Minneapolis Star Tribune newspaper.

In 2013, the inaugural Schneider award went to Ryan Gabrielson of California Watch, part of The Center for Investigative Reporting, for a series exposing the routine failure on the part of police to protect the developmentally disabled at California care institutions.

The contest seeks to recognize journalism that sets a new and higher standard for reporting on disability issues and people with disabilities, said Kristin Gilger, associate dean of the Cronkite School and director of the NCDJ. “This year’s winners did that far beyond our expectations, and they did it by telling compelling human stories and by holding power accountable,” she said.

Schneider pointed out that millions of people have some form of disability, yet they are frequently under-covered by the media, or they are depicted in stereotypical ways. In establishing the contest, “I wanted to help highlight good stories, and I chose to work with the NCDJ and the Cronkite School because of their commitment to fair and accurate journalism that includes diversity,” she said.

Reporter , ASU Now