There could have been no better place for Carlito Lebrilla’s research to thrive than UC Davis.
“What’s around you influences what you do scientifically,” the chemistry professor said. “It’s only been possible in Davis because of who is here, because we are unique in having an agricultural school, veterinary school and a medical school all in one location.”
Now, in recognition of his quarter-century of pioneering work on how complex sugars affect health and nutrition, Lebrilla’s colleagues in the Davis Division of the Academic Senate have chosen him as the 2018 recipient of the division’s highest honor: the Distinguished Research Award, known up until this year as the Faculty Research Lecture award. The recipient still gets to deliver a lecture — and Lebrilla will do just that Monday, April 30, as part of the university’s annual Academic Senate-Academic Federation awards program.
Before we get into Lebrilla’s work, some basics: Complex sugars, also known as oligosaccharides, or glycans, are organic molecules made up of chains of saccharides, the ring structures that make up sugars. Sucrose, or table sugar, is made of two such rings; glucose is a single ring, but many different combinations are possible.
“Cells are coated in glycans, but back then people didn’t realize how important they are,” Lebrilla said. “Since then we’ve found that they are important in cancer, in immune diseases and in food.”
Other molecules with saccharides attached take the prefix “glyco.” For example, a glycoprotein is a protein molecule with a sugar attached.
Complex sugars had been underexplored when Lebrilla started his work. Unlike proteins, oligosaccharides are not directly coded by DNA, and they were generally thought of either as a general food source or structural material.
Lebrilla began collaborating with Jerry Hedrick, now professor emeritus of molecular and cellular biology, who had discovered that glycan-type molecules coated the surfaces of sperm and eggs and played a role in fertilization. Lebrilla’s lab developed methods to characterize these molecules and branched out into other fields with collaborators from across the campus.
Milk and microbes
One of those collaborations began when Professor Bruce German, Department of Food Science and Technology, came to see Lebrilla with a puzzle. Milk contains large amounts of oligosaccharides — in fact, the chemists were using them as standards for their experiments. These sugars had been identified as far back as the 1930s, but no one knew what they did because they cannot be digested by humans.
Lebrilla’s lab developed tools to measure these saccharides in milk, feces and urine, so they could measure exactly what went into an infant and what passed through. Working with Professor David Mills, microbiologist in the Department of Food Science and Technology, they discovered that these sugars were nourishing one particular microbe, Bifidobacterium infantis, in the infant digestive systems.
“Simple sugars are food for everything, but the complex sugars feed just one bacteria found in healthy infants,” Lebrilla said. Because B. infantis can break down the complex, indigestible sugars and generate other useful compounds, it helps nourish the baby. Mills’ work also showed that for a variety of reasons, B. infantis is disappearing in American babies.
The research collaboration on milk and microbes led to a startup company, Evolve Biosystems, that now has 50 employees. Evolve makes probiotics to encourage a healthy environment in the infant gut and prevent digestive disorders.
The idea that specific components in food nourish bacteria in our gut rather than feeding us directly may apply to adults, too. It’s becoming clear that there is much more interaction going on between our food and our gut microbes than previously suspected.
“We know very little about what we eat, at a structural level,” Lebrilla said. “What if you can tailor the carbohydrates in your diet to match your gut bacteria?”
Most work on microbiomes — the communities of bacteria we carry around with us — focuses on cataloging the microbes present, Lebrilla said.
“But how do you change the population? The missing part is how you feed your microbiome, and that all goes back to chemistry.”
On the other side of the causeway, Lebrilla’s collaborations with oncologists and researchers at the UC Davis Comprehensive Cancer Center have led to exciting new tools to diagnose ovarian, breast and prostate cancer.
All body cells are coated with oligosaccharides and other carbohydrates. When cells become cancerous, these coatings can change, and new molecules are shed into the blood.
Working with Suzanne Hiyamoto, Kit Lam and others at UC Davis Health and the Comprehensive Cancer Center, Lebrilla characterized oligosaccharides and glycoproteins associated with cancer. That led to two more startup companies: Glycometrix, founded in 2006, and more recently to Venn Biosciences, which is in an early phase of development.
Additionally, Lebrilla’s lab has a long-standing partnership with Agilent, which manufactures the mass spectrometry instruments specially designed to study the structures of oligosaccharides and other carbohydrates.
“Agilent uses a lot of our data, and they hire my students,” Lebrilla said. “We’ve had a good collaboration.”
If microbes give back to their host when nourished in the right environment, then Lebrilla’s research has been nourished by the environment at UC Davis to give back in all kinds of different areas.
“I’ve been fortunate to have good collaborators and good students, and then everything else fell into place,” he said.