The perfect pair: How biology and engineering are creating new breakthroughs in human health

Pairings like peanut butter and jelly or milk and cereal are iconic. But the concept of creating winning combinations is not limited to the kitchen; it is a fundamental principle driving the revolutionary field of synthetic biology, or synbio.

“Synbio is a cutting-edge discipline at the intersection of biology and engineering, where scientists design and construct new biological components and systems, or re-engineer existing ones found in nature,” said Rahul Thakar, Ph.D., a program officer in NHLBI’s Division of Cardiovascular Sciences and co-organizer of a recent workshop on using synbio to improve heart, lung, blood, and sleep conditions. “It's biological design with intent.”

Synbio increases scientists' ability to make targeted models mimicking human diseases that can be applied more easily when doing research on humans is not possible. Cardiovascular disease and circadian rhythm disorders that impact sleep are among the many conditions researchers are looking at.

“We have learned a lot about systems using animal models in scientific research to understand human disease, but mice and flies and other model systems are their own organisms with their own genetic fingerprints – and they’re certainly not humans,” said Shilpy Dixit, Ph.D., a program officer in NHLBI’s National Center for Sleep Disorders Research and co-organizer of the workshop. “Synbio models, such as engineered tissues and organoids, are designed to be more representative of a human system.”

One step closer to precision medicine

Synbio’s power comes from the tools and techniques that allow the customization of medical treatments that fit the unique genetic and molecular profile of each patient. For example, synbio makes it possible to design highly specific drugs that can target individual genetic mutations or pathways involved in a patient's disease. It also enables the creation of biosensors that can monitor a disease at the molecular level.

Dixit explained that animal and cell models have allowed researchers to make great strides in understanding the molecular and cellular pathways of treatments. “Synbio could potentially assist with the fine-tuning of treatments,” she said.

Thakar gave an example of dimmer lights to explain the concept: “With the old way of doing things, once we knew the treatment, we could turn the treatment on and off like a normal light switch.” he said. “But with synbio, certain cell therapies might be able to sense exactly what a specific person may need in their body, and that therapy may be tunable or programmable, much like a dimmer switch.”

Groundbreaking research highlights synbio’s potential

NHLBI is already funding exciting research in this area. For example, a start-up company, KaloCyte, has received a Small Business Innovation Research grant to combat a shortage of blood exclusively used for emergencies when stored blood products are unavailable or in short supply. KaloCyte is creating an artificial red blood cell inspired by nature. The technology uses purified human hemoglobin, a protein that carries oxygen from the lungs to the body's tissues and organs. It’s encased in a soft lipid nanoparticle shell designed to mimic natural red blood cells, and it’s also a universal option for all blood types. It can be freeze-dried as a powder for long-term storage without refrigeration, giving it a self-life of two years in contrast to the 42-day shelf life of normal red blood cells.

Another researcher receiving NHLBI funding is Ying Mei, Ph.D. and his Clemson University colleagues, who are pioneering the use of silicon nanowires to better generate mini beating hearts, known as organoids, in a dish. Turning human stem cells into the various cells that grow the heart has shown potential in providing a patient-specific strategy to treat cardiovascular disease. Yet, despite great progress in this field, scientists are grappling with a few challenges:  in some of the early pilot work, the heart organoids are sometimes underdeveloped, they assemble incorrectly, or they present a risk of arrythmias after transplantation. Mei’s lab is addressing all this by incorporating electrically conductive silicon nanowires into the mini hearts, which gives them electrical stimulation through pacemaker-like stimuli. Their work has shown that the use of nanowires leads to better structural and functional development and a significant decrease in spontaneous heart beats of organoids.

Finally, NHLBI-funded work by Deblina Sarkar, Ph.D., and her team at Massachusetts Institute of Technology is showing promise as a bridge between nanotechnology and biology. Sarkar is designing wireless sub-cellular sized electronics, much smaller than even a single cell, which can match the size of structures inside the cell. These electronics can sit inside the cells or in the space between the cells and can coexist with the biological structures without damaging them. Her technology, known as cell rover, works like an antenna that can live inside a living cell and conduct smart intracellular sensing. Applying the cell rover to heart conditions will allow the researchers to be able track, control, or alert when abnormal events like arrythmias occur.

Thakar said all this work shows that using innovation and combining fields in synbio are shaping what’s ahead in the world of finding cures for human diseases. “Synbio is promising a future where the unimaginable becomes possible,” he said. “It will be fascinating.”