Science at Lawrence Livermore National Laboratory (LLNL) is what synthetic biologist and postdoctoral researcher Sean Leonard calls a "team sport." This is one of the aspects he enjoys the most about working in a national laboratory environment.
"I'd say my military experience fundamentally shaped how I approach science," said Leonard. "In the Army, I learned that I like being part of a team, working toward a common goal."
After completing his bachelor's degree in molecular biology on a Reserve Officers' Training Corps (ROTC) scholarship, Leonard served as a chemical officer for four years in the U.S. Army, followed by three years in the National Guard. In this position, he ensured his unit was trained and ready to respond to chemical, biological, radiological, nuclear and explosive (CBRNE) incidents. While deployed in Iraq, Leonard and his platoon ensured the safety of the explosive ordinance disposal teams, providing security escort services to the teams as they moved around the battlefield to locate, secure and dispose of any explosive devices.
Following his military service, Leonard resumed his educational journey and discovered his passion for microbiome engineering. His Ph.D. research focused on the development of synthetic microbiology tools to genetically engineer the bacteria that live inside bees. Bees often face the risk of colony collapse, but by boosting their immune systems with engineered bacteria, they are better equipped to fend off threats like varroa mites or deformed wing virus - two major contributors to colony collapse.
A healthy bee population is essential for agricultural production, as crops that are pollinated by bees end up producing a larger yield.
"The western honey bee, for example, is kind of like a tiny cow. They are used in agriculture throughout the United States and the rest of the world," Leonard said.
Since joining LLNL in 2021, Leonard's Ph.D. research has blossomed into his current biocontainment efforts. Working at the intersection of computational and experimental research, Leonard studies different biocontainment methods for controlling how genetically engineered microorganisms (GEMs), such as bacteria, will function in the environment. This research effort is part of the Department of Energy's Secure Biosystems Design Scientific Focus Area.
GEMs have many applications - from therapeutic drug discovery, manufacturing and delivery to improving agricultural yields, biofuel production, mineral extraction and waste degradation. For instance, using GEMs in soil provides a climate-friendly alternative to synthetic fertilizers, whose production contributes to climate change. Like in the honey bee, GEMs can also be used to fight off and treat diseases in the human gastrointestinal system. Regardless of their use cases, Leonard's job is to ensure these GEMs are safe to release into the environment.
To do this, he is studying the functionality of engineered auxotrophs and overlapped genes to enhance the genetic stability of GEMs. An auxotroph is a microorganism that is missing essential genes that are critical for survival. The intentional deletion of these genes removes their ability to be self-sufficient, making them easier to contain in the environment.
Gene overlapping, on the other hand, involves taking a gene of interest and an essential gene and synthetically encoding or "entangling" them within the same DNA sequence to constrain the evolutionary outcomes of the gene of interest. "We take a gene that makes a product that we care about and we overlap it with an essential gene for the bacteria," Leonard explains. "The bacteria have to keep making the gene that we care about, it can't mutate or destroy that gene without also impacting the essential gene." A mutated gene would lead to the bacteria's demise.
Using advanced computational models and LLNL's high-performance-computing resources, Leonard can quickly test hundreds of thousands of gene variants. He said: "We are essentially looking at how we can mutate and redesign certain genes while still keeping them functional so that they can continue to produce what we need."
When Leonard isn't discovering new and creative ways to contain GEMs, he can be found conducting bumblebee surveys around the Bay Area in his free time.
