Columbia engineers develop a new platform that recreates cancer in a dish to quickly determine the best bacterial therapy.
Engineering bacteria to intelligently sense and respond to disease states, from infections to cancer, has become a promising focus of synthetic biology. Rapid advances in genetic engineering tools have enabled researchers to "program" cells to perform various sophisticated tasks. For example, a network of genes can be wired together to form a genetic circuit in which cells can be engineered to sense the environment and modulate their behavior or produce molecules in response.
The image shows engineered bacteria (green) in tumor spheroids cultured in a multi-well plate.
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Recent research has found that many bacteria selectively colonize tumors in vivo, prompting scientists to engineer them as programmable vehicles, biological "robots" in other words, to deliver anticancer therapeutics. Researchers are also developing new, "smart" medicines by programming bacteria to tackle other diseases, such as gastrointestinal disease and infections. Key to advancing such "living medicines" is being able to identify the best therapeutic candidates.
Researchers at Columbia Engineering report in PNAS that they have developed a system that enables them to study tens to hundreds of programmed bacteria within mini-tissues in a dish, condensing the time of study from months to days. As a proof of concept, they focused on testing programmed antitumor bacteria using mini-tumors called tumor spheroids. The speed and high throughput of their technology, which they call BSCC for "bacteria spheroids co-culture," allows for stable growth of bacteria within tumor spheroids enabling long-term study. The method can also be used for other bacteria species and cell types. The team, led by Tal Danino, assistant professor of biomedical engineering, says that, to their knowledge, this study is the first to rapidly screen and characterize bacteria therapies in vitro and will be a useful tool for many researchers in the field.
"We're very excited at how efficient BSCC is and think it will really accelerate engineered bacterial therapy for clinical use," Danino says. "By combining automation and robotics technology, BSCC can test a large library of therapies to discover effective treatments. And because BSCC is so broadly applicable, we can modify the system to test human samples as well as other diseases. For example, it will help us personalize medical treatments by creating a patient's cancer in a dish, and rapidly identify the best therapy for the specific individual."
MEDICA-tradefair.com; Source: Columbia University School of Engineering and Applied Science