In high school,” Daniel Amador-Noguez recalls, “I took a science class where one of the lectures was all about the future – where the research was taking us, what were some potential future discoveries – and I thought, ‘oh, all this sounds really cool, so how come it hasn’t happened yet?’”
Seventeen years later, it’s not at all difficult to square that eager young man with the energetic scientist Amador-Noguez has become. An assistant professor of bacteriology at the University of Wisconsin–Madison and researcher at the Great Lakes Bioenergy Research Center (GLBRC), Amador-Noguez emanates anticipation, for next week’s result, the future of his research, and the future of biofuels.
“It’s difficult to come up with a biological process that isn’t affected by bacteria,” he says. “They are virtually everywhere, not just in the environment but also inside our bodies. And if we can improve our understanding of microbes we can do a lot of enormously important things, including improving biofuels.”
Amador-Noguez’s lab focuses on understanding metabolism in biofuel-producing bacteria with the goal of engineering microbes that can more efficiently convert plant biomass to energy. It’s exciting research, but it’s also the kind of data-driven work that Amador-Noguez hungered for from a very early age.
Growing up in Pachuca, a small city in central Mexico, in the 1980s Amador-Noguez struggled to find information on biology, the subject that interested him most. Science education in Mexico at that time was not strong, the Internet was not yet in widespread use, and bookstores were scarce, so Amador-Noguez found himself reading and re-reading the same encyclopedia periodical his mother had arranged to be sent to the house.
“I must have read that encyclopedia three or four times by the time I was nine or ten,” he says. “My favorite volume had a section on genetic mutations with all this classic imagery of flies, where you have all these different flies with three eyes or four wings. It’s a bit creepy but for a kid that’s really interesting!”
After high school, Amador-Noguez headed to the Monterrey Institute of Technology in northern Mexico, where he had his first real exposure to science, including laboratory research. Since he hadn’t been able to find a good biology program in Mexico, he majored in chemistry.
After graduating from Monterrey in 2001, Amador-Noguez pursued a doctorate in molecular genetics at Baylor College of Medicine in Houston, Texas. While studying the molecular mechanisms of aging in the long-lived Ames Dwarf mice and Little mice, Amador-Noguez discovered that liver metabolism played a key role in the mice’s longevity. His research has focused on metabolism ever since.
He left Baylor with doctorate in hand in 2007 and headed to Joshua Rabinowitz’s lab at Princeton University to do a postdoctoral fellowship in cellular metabolism. He began using mass spectrometry, an analytical chemistry technique, to study the metabolism of bacteria related to biofuel production, and there his interest in biofuels was born.
After five years at Princeton, Amador-Noguez joined UW–Madison and GLBRC in the fall of 2013. To study bacteria in his lab, he now uses metabolomics, a relatively new, systems-level approach to understanding the behavior of metabolites and the regulation of metabolism in microorganisms.
Amador-Noguez uses analytical tools such as mass spectrometry and liquid chromatography, which enable him to identify and measure most of the metabolites inside bacteria, as well as determine the bacteria’s metabolic flux, or which of the bacteria’s metabolic pathways are the most active (or inactive) as the cell converts nutrients into the energy and building blocks it needs to grow.
Metabolic flux, the extent to which carbon is passing through one metabolic pathway versus another, is of particular importance to biofuel production. Often, the way to engineer bacteria that are more efficient at converting biomass into biofuels is to maximize flux through pathways known to be involved in biofuel production.
The linked nature of metabolic pathways also makes inhibition of any one pathway a significant issue in studying bacteria; if one pathway is not working, a cell will simply shut down the rest of its metabolism.
In one recent GLBRC project, Amador-Noguez and his team sought to understand how a particular toxin inhibits the conversion of plant sugars into biofuels. The toxin in question is produced from lignin – the woody backbone of plants – during the process of breaking down plant biomass into its sugar components such as glucose.
Amador-Noguez discovered that, in general, these “lignotoxins” are powerful inhibitors of the enzymes the cell needs to synthesize nucleotides, which are essential to the cell’s DNA.
Now that Amador-Noguez knows which enzymes are affected, he and other researchers can find a way to direct those particular enzymes to be more resistant to lignotoxins. Or he can break the regulatory connections between nucleotide biosynthesis pathways and fermentation pathways so that the bacteria would simply remain unaware that a particular biosynthetic pathway was not functioning properly, and would thus continue to produce biofuels.
Looking to the future, Amador-Noguez is excited about the possibility of developing new metabolomics tools that could help reveal how metabolism is regulated within entire bacterial communities, and not just in isolated bacterial species. He says that much remains unknown about how bacteria play nice with one another but that gaining an understanding of the community’s rules could yield powerful results.
“If we could understand how different bacteria interact with each other metabolically in these complex bacterial communities we could do a lot of things,” he explains. “We could understand what shapes the bacterial communities living inside of our bodies, which would have important ramifications for human health, and we could engineer each bacteria in those communities to specialize in doing one thing, which could make the process of biofuel production much more efficient.”
“Biofuels,” he adds, “are an important solution for many of our energy issues. We’re always going to need fuel and we’re always going to need chemicals. And the biological production of biofuels and high-value chemicals from plant biomass is one of the most promising strategies for the sustainable generation of these essential commodities.”
Like many scientists working today on energy-related research, Amador-Noguez remains motivated by the impact his day-to-day research could have on the national and global energy picture, as well as by his long-burning desire to make important advances happen.
“The fact that what we’re doing can contribute to solving big problems in society, that is very motivational,” he says.