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Dr Stewart Loh awarded $1.5 million federal grant for project combining protein and DNA engineering

Upstate Medical University professor Stewart Loh, PhD has been awarded more than $1.5 million from the National Institute of General Medical Sciences to combine two different fields of biomedical engineering in a unique way.

Loh’s lab has been engineering proteins for 20 years, turning them into molecular switches that can be used to detect diseases and kill infected or diseased cells. Now, he plans to bring his work with proteins together with DNA engineering.

“Protein engineering is hard—it takes people a long time to develop a protein switch—but once you have it, you can do amazing things with it,” said Loh, professor of biochemistry and molecular biology. “DNA engineering is almost the opposite. It’s easy to design DNA structures but they can’t perform complex biological tasks.

“In our NIH-sponsored project, we’re building a few select protein switches that have powerful biological activities and using DNA engineering to turn on those activities by DNA or RNA sequences of our choice, such as those from coronavirus or cytomegalovirus,” he said.

One practical application of this work is helping transplant patients detect, or even avoid outright a cytomegalovirus (CMV) infection. CMV is a virus that infects over half of all US adults by the age of 40. While CMV remains in a person’s body for life, for most their healthy immune system keeps the virus from causing illness. In transplant patients, however, CMV is the leading cause of death and illness as their immune systems aren’t able to fight the virus. Loh thinks protein and DNA bioswitches can help not only detect CMV in patients to help manage infection but potentially could eliminate CMV before the transplant.

“Our protein switch senses whether CMV DNA is present, and if it is, it turns on and destroys the infected cell’s RNA, killing it,” explains Loh. “The remaining uninfected cells can be transplanted safely to the recipient. We’re also making another switch that emits light when it binds CMV DNA, which we intend to use to detect CMV in the blood of donor and recipient, to prevent and manage CMV infection.”

Loh said he’s working with Upstate professors Gary Chan, PhD, an expert in CMV biology, and Reza Saidi, MD, chief of transplant services, on this use of his bioswitches.

“We are particularly excited about the potential of this new NIH-sponsored project to translate our biomedical research into the clinic,” Loh said. “It’s the dream of basic scientists such as myself to be able to contribute directly to the Upstate’s health care mission, in addition to making fundamental discoveries.”

Loh thinks this is just the beginning of possible uses for this combination of protein and DNA bioswitches.

“Imagine if you could unlock large areas of the proteomes of humans and other organisms to this type of control,” Loh noted. “Enzymes and proteins do all sorts of useful things. DNA is what makes humans different from one another and from other creatures. Combining protein and DNA engineering can potentially be used to activate a protein of choice in response to a DNA sequence that is unique to an individual or to an invading pathogen. This would represent a new level of medicine that is personalized to the individual and to the strain of virus. For now, we’re focusing on CMV applications but the next logical targets are other infectious diseases.”

The National Institute of General Medical Sciences (NIGMS) supports basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment, and prevention.​