GUO wins NSF CAREER Award to Boost Biocircuit Engineering
Dr. Liang Guo has some interesting lab mates, not typically associated with electrical and computer engineers (ECE) at The Ohio State University.
Sea slugs move slowly around inside aquariums. Microscopes are hooked up to computers. Petri dishes hold specimens behind glass.
In the quest to find a cure for Parkinson’s and other diseases, Guo is pioneering an entirely new pathway for neural implant science. He is at the forefront of what he calls biocircuit engineering.
The research recently earned him the coveted National Science Foundation (NSF) Faculty Early Career Development (CAREER) Award. It is given to support the work of the nation’s most promising junior faculty who exemplify the role of teacher-scholars through the integration of outstanding research and excellent education.
Guo earned $500,000 over the next five years to advance his research proposal, “CAREER: Multicellular Biological Neural Pacemaker.”
To describe biocircuit engineering, Guo explained how each cell in the body has a natural function. What if these specific-functioning cells are placed elsewhere inside the body to grow into nerves to assist a diseased organ, or to stimulate a neural pathway in the brain to help restore activity? Feasibly, he said, the cell could connect to a rat’s skeletal muscle to pace the animal's muscle contractions and control breathing functions.
From there, he said, imagine implanting a cardiac pacemaker, grown from the patient's own cells, back inside the body where it can assist a diseased organ – powered simply by the natural flow of blood.
The concept is an innovative realm of research, which Guo hopes will cure neurological diseases.
“The best way is to learn from nature,” he said. “In this process, we can learn how the neurobiological circuits are designed from living cells. Once we learn enough, we may be able to expand to artificial designs on those biological principles. That’s my whole philosophy.”
In one project tied to his biocircuit engineering program, Guo and his team are researching how simple sea slug cells might help create new circuits inside the body to cure neurological diseases.
“We understand this circuit very well. Cell by cell," he said about the sea slug cellular structure. "Can we isolate those cells and reconstruct the circuit in a culture dish? Furthermore, can we re-implant the constructed circuit back into the animal to see if it can substitute?”
For his student team members, the opportunity to work with Guo is unique.
“When I was looking for research opportunities in neural engineering, I wanted to find a researcher who had ambitious ideas and was willing to take the risk to make them happen. Dr. Guo was just that when I met with him. His biocircuit approach is the type of project that I believe could have profound significance in developing the next generation of implantable bio-devices,” Jordan Prox said, a graduate research associate and Biomedical Sciences Graduate Program student.
Fellow team member Aaron Argall, also a BSGP student and graduate research associate, said what initially drew his attention to Guo's work was the interdisciplinary nature of his research.
"Leveraging principles from electrical and tissue engineering to find solutions to neuroscience problems with a focus in neuroprosthetics, I found a unique niche that I could contribute to based upon my previous research experiences," Argall said. "I knew from the beginning a lab solely using one field to answer a question wasn't what I wanted out of a Ph.D. It was with great joy that I came across Guo's research that seemed to coalesce my research interests."
Argall said he hopes to do transformative research to have a positive lasting impact on human health and disease.
"My current aspiration is to be a physician scientist studying neural regeneration, using a multifaceted approach going from bench to bedside," he said.
For NSF, Guo is looking at utilizing heart cells and neurons from rats to create an artificial neural stimulator in a petri dish.
“That’s how this project was originally envisioned. But before we can test it in the brain, we need a much simpler model to demonstrate the functional feasibility. So, we chose a skeletal muscle as the testbed. In doing so, we will harvest the heart cell as a signal source. It will beat automatically," he said.
From there, the artificial circuit can target a skeletal muscle.
“But we need something in between as an interconnect. We know that skeletal muscle is connected by motor neurons. Our idea is, can we connect the heart cells to motor neurons and then allow the motor neurons to connect to the muscle,” Guo said.
Powered by the heartbeat, the motor neurons cause the muscle to contract.
So how do they use this technique to help people? Is there any disease affecting respiration they could focus on?
Guo said they centered on curing chronic hypoventilation, which is caused by damage to the phrenic nerve in the diaphragm muscle. This leads to the inability of the respiratory musculature to exchange gases, resulting in excessive carbon dioxide and lack of oxygen to the tissues.
“Even if the muscle is intact, the patient cannot breathe. They will rely on a ventilation machine. They need to be tethered to the machine,” Guo said. “Can we use this biological neural pacemaker, built by the patient’s own cells? If we can harvest the patient’s skin cells, convert them to induced pluripotent stem cells (iPSC), and then reconstruct them into either heart cells or motor neurons. Then, if we can create such a biocircuit using these iPSC-derived cells, and we connect our circuit to the distal terminal of the phrenic nerve, then our motor neurons will automatically grow into the diaphragm muscle. We have the possibility to pace the breathing at approximately 1 Hertz.”
The studies right now are done in the lab, he said, just to show the possibility. The immediate goal is to see if they can pace a muscle in a culture dish.
“By the end of the project, we hope to have the skills and knowledge to advance to implantation studies,” he said.
In some cases, Guo said, many universities are pursuing conventional electronic neural implant research toward treatments to neurological diseases. In the case of his team, they are entirely pioneering the emerging field of biocircuit neural implants.
The reason their work stands alone, he said, is the integrative scientific knowledge it requires.
“The challenge is people need a multi-disciplinary background. We are creating circuits, but we are not using conventional materials. It requires people with an electronics, or electrical engineering background, rather, who can work with biology,” Guo said. “These types of scientists are rare in the field, which creates a technical barrier for people to jump in. We need people to develop these types of details. We are at the forefront of this emerging direction.”