How to entertain a gene circuit without exhausting its host

ASU's Xiaojun Tian wins NSF CAREER Award to dissect foundational problems for synthetic biology


February 25, 2022

Synthetic biology is a rapidly developing field at the frontier of science. It applies engineering methods to direct the behaviors of living systems for beneficial outcomes. For example, genes could be configured into circuits that are implanted into human body cells to guide them in detecting and combating deadly diseases. 

A genetic circuit is more an abstract concept than a physical construction. One gene segment encodes or produces a particular protein that either activates or inhibits the expression or protein production of another gene segment. Continuing this sequence results in a chain of influence or inducement that functions as a circuit to drive the actions of the cell in which it is planted. ASU Assistant Professor Xiaojun Tian in his laboratory. Assistant Professor Xiaojun Tian explores the molecular and cellular mechanisms that natural cells adopt to both host synthetic gene circuits and constrain their behavior. This groundbreaking work could enable the synthesis of new therapeutics, the expansion of sustainable agriculture and the production of renewable resources. Photo courtesy Erika Gronek/ASU Download Full Image

The potential of this complex design work has expanded during the past three decades into a variety of diagnostic and therapeutic applications. But current approaches to development have reached a bottleneck due to the growing size and complexity of synthetic gene circuits.

“Synthetic biologists have been designing circuits with the expectation that they function orthogonally, or independently, of their host cell background. But that is not the case for most of them,” says Xiaojun Tian, an assistant professor of biomedical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University. “They actually steal significant amounts of resources created by the host cell for its own physiological functions, such as growth or survival. So, the circuits impose a real metabolic burden.”

Resource competition is not the only challenge. The successful growth of host cells can also cause problems. The expanding cellular environment dilutes the expression of the synthetic genes forming a circuit. It creates a feedback loop that compromises the circuit’s ability to perform as intended.

These unwanted interactions are significantly hindering the design and construction of circuits that can be applied to the synthesis of new therapeutics, the expansion of sustainable agriculture and the production of renewable resources. In order to address these contextual challenges and enable further progress, Tian is leading novel research within the School of Biological and Health Systems Engineering, one of the seven Fulton Schools at ASU.

His approach is promising enough to have won a National Science Foundation Faculty Early Career Development Program (CAREER) Award for nearly $700,000. CAREER Award recognition is reserved for young researchers who show the potential to be academic role models and advance the missions of their organizations. Awardees each receive support for five years to further their highlighted research.

Tian will devote his expertise to creating a better understanding of the molecular and cellular mechanisms that natural cells adopt to “entertain,” or host, synthetic gene circuits and to constrain their behavior. He and his team will develop a library of circuits to help dissect the fundamental processes at work and then develop general modeling frameworks to accurately predict behavior.

These frameworks will help create practical strategies to control circuit-host interactions and optimize functions at the level of individual cells, as well as for multi-cellular populations of a single type and broader ecologies involving multiple cell types.

Of course, such complex and groundbreaking work generates surprises. Tian says observations in the lab are frequently contrary to the predictions of theoretical analysis, and each unexpected result demands troubleshooting and more testing.

“But these surprises are good things, since they move us in new directions,” Tian says. “And the new directions are revealing foundational problems of circuit-host interactions.”

“These issues are faced by everyone in this field,” he adds, “so our work with underlying mechanisms can move all of us toward development of synthetic biology products that are reliable and robust enough to address many different challenges.”

Gary Werner

Science writer, Ira A. Fulton Schools of Engineering

480-727-5622

Learn, earn and return: School of Molecular Sciences supports military students


February 25, 2022

Since launching the first online degree in 2017, the number of chemistry and biochemistry undergraduate majors in the School of Molecular Sciences at Arizona State University has more than doubled. Additionally, the new online student group is significantly more diverse than the on-ground student population, at 65% female and with four times as many Black students and six times as many military and veteran students compared with on-ground students.

One of these military students is Cory Smith, an online biochemistry major currently serving in the Air Force as a U-28A mission pilot, who recently completed his seventh deployment in the Middle East. Smith has his sights set on earning entry into medical school, and then returning to active duty as a military physician. Side-by-side portraits of Cory Smith, ASU School of Molecular Sciences biochemistry student. In the left photo, Smith wears military fatigues. In the right photo, Smith wears a lab coat, safety goggles and a face covering. Cory Smith, an online biochemistry major, currently serves as an Air Force as a U-28A mission pilot and attended the compressed organic chemistry labs in summer 2021. Download Full Image

Despite multiple deployments and a variety of temporary-duty assignments, Smith has managed to maintain a 4.0 GPA.

“I have taken courses while in several different states, as well as multiple countries across Europe, the Middle East and Asia,” Smith said. “I even had to ship myself several weeks’ worth of chemistry lab materials so I could complete labs while on the road. Without programs like this one at ASU, it would have been much more difficult to continue serving while making progress on my journey to become a doctor.”

In the summer of 2021, Smith travelled to Arizona and the Tempe campus, where he met with students and faculty he otherwise only knew from online interactions, to complete his organic chemistry laboratory courses and to feel like a genuine Sun Devil.

“Cory is an enthusiastic and dedicated student, and despite his busy flight schedule, he regularly attends office hours and remains active in the class. I'm glad that SMS is able to support military students like Cory, who is serving our country, through the online program,” said Ara Austin, faculty member in the School of Molecular Sciences and director of online engagement and strategic initiatives in The College of Liberal Arts and Sciences.

Last year, Smith was the recipient of the SMS Veterans Scholarship. This scholarship supports undergraduate students, whether military veterans or children of veterans, who are pursuing a degree and career in the molecular sciences.

“Earning this scholarship means a great deal to me,” Smith said. “To have my hard work recognized by my professors and the (school) community provides meaningful validation and motivation for me to continue performing well.”

Many ASU students are able to reach their goals because of the generosity of alumni, school community members and employees of ASU, among others. Smith is grateful to those who have contributed to ASU to make this and other scholarships available to him and for other students.

“I am sincerely grateful to have been chosen as a recipient of the SMS Veterans Scholarship," he said. "Scholarships are especially important for online students because the recognition helps strengthen their connection to the school.”

“One unexpected benefit from providing online programs is the extent to which they have opened access to college education for students from more diverse backgrounds," said Ian Gould, associate dean of online innovation in The College. "Going online has had a larger impact in this regard than any other program we have tried over the last few years. Cory is a perfect example of this. I am always astonished that students like Cory can carry heavy life responsibilities while at the same time maintaining a perfect GPA in challenging science courses. We are very proud of Cory.”

James Klemaszewski

Science writer, School of Molecular Sciences

480-965-2729