Skip to main content

Winner-take-all synthetic gene circuit opens new pathways to disease treatment

Division of circuit workloads will make therapy more effective

Winner-takes-all synthetic gene circuit

February 08, 2021

A new process for inserting synthetic gene circuits into host cells, developed by a team of bioengineers at Arizona State University, has broad implications for improving the effectiveness of a range of disease therapies.

Synthetic biology is an interdisciplinary research field that uses engineering principles to create biological components that don’t exist in the natural world. These synthetic components mimic naturally evolved organisms, but are customized to fight disease, including cancer.

A paper recently published in Nature Communications, “Winner-Takes-All Resource Competition Redirects Cascading Cell Fate Transitions,” outlines how gene circuits can be reconfigured so that they do not overwhelm the host cells.

“We connect circuits together like a Lego chain and insert them into a host cell,” explained lead author Xiaojun Tian, an assistant professor in the School of Biological and Health Systems Engineering at ASU. “The circuits in the chain are designed to perform different functions, but they must compete with each other for the cell’s limited resources.”

Novel synthetic gene circuits within one host cell

Assistant Professor Xiaojun Tian’s research reveals a novel winner-take-all resource competition between synthetic gene circuits within one host cell. Graphic created by Xiaojun Tian/ASU

Competition for resources has been a challenge in the synthetic biology field since its inception 20 years ago. 

“We would find circumstances where one gene circuit in a chain would consume 90% of a host cell’s available resources, leaving only 10% for the remaining circuit,” Tian said.

Tian’s team devised a way to insert individual gene circuits into multiple host cells that work collectively. Each cell performs a specific function, eliminating the undesired competition for resources of any host cell.

“Instead of dividing resources, each cell can perform 100% of its assigned workload,” said Tian. “The host cells perform as a connected unit without depleting any one cell’s resources — and each gene circuit becomes a winner.”

The technology has broad implications for cancer treatment, with future applications for other diseases on the horizon. Ninety percent of cancer deaths are due to metastasis — the spread of cancer cells to other sites in the body. However, treatment resistance is still a major problem in cancer therapeutics.

“There are many different kinds of cells in a cancer mass,” said Tian. “Some cells are responsive to chemotherapy and others are not, causing treatment resistance."

New multitasking synthetic gene circuitry configuration can be constructed to prevent the cells from metastasizing in the first place, while simultaneously making them more receptive to treatment. 

Tian explains that multicellular synthetic circuits will be a much more effective way to treat cancer.

The research team also includes Rong Zhang, Hanah Goetz, Juan Melendez-Alvarez, Jiao Li and Xiao Wang from ASU and Tian Ding from Zhejiang University in Hangzhou, Zhejiang, China. The research was funded by the National Science Foundation and the ASU Dean’s Fellowship.

Top photo by Gladson Xavier from Pexels.

More Science and technology


Photo of student Cartner Snee and professor Kevin McGraw standing in a backyard

AI-equipped feeders allow ASU Online students to study bird behavior remotely

ASU Online students are participating in a research opportunity that's for the birds — literally. Online Bird Buddies is a project that allows students to observe birds remotely, using bird feeders…

A robotic hand reaches up into a network of connected lines and dots, an unseen light source illuminates the hand.

National Humanities Center renews partnership with Lincoln Center for responsible AI research

The National Humanities Center has announced  that Arizona State University's Lincoln Center for Applied Ethics is one of four organizations to receive funding for the second phase of their…

Illustration of a semiconductor being put together

Advanced packaging the next big thing in semiconductors — and no, we're not talking about boxes

Microchips are hot. The tiny bits of silicon are integral to 21st-century life because they power the smartphones we rely on, the cars we drive and the advanced weaponry that is the backbone of…