Unraveling Bacterial Genomes

At the University of Utah's Department of Chemistry, faculty member Aaron Puri and graduate student Delaney Beals are pioneering research to decode bacterial genomes by understanding their natural environments. Their project, which began with Puri's pilot experiments during his postdoctoral fellowship, focuses on linking methanotroph phenotypes to genotypes using a spatially resolved model ecosystem.

Graduate student Delaney Beals and faculty member Aaron Puri

Puri, who started his research group in 2019, brings a diverse and impressive background to the project. With triple bachelor's degrees from the University of Chicago, a PhD in chemical and systems biology from Stanford University, and postdoctoral research at the University of Washington, Puri's expertise spans chemical tools for host-pathogen interactions and genetic tools for methane-oxidizing bacteria. Now a faculty member in the Henry Eyring Center for Cell & Genome Science, his work centers on the biological chemistry of bacteria that grow on one-carbon compounds like methane and methanol.

Beals, a fifth-year PhD candidate, contributes vital expertise in the chemical ecology of methane-oxidizing bacterial communities. Originally from North Carolina with a bachelor's from UNC Asheville, Beals was drawn to Puri's lab due to its focus on bacterially derived natural products. "By studying how a particular microbe behaves in the natural environment versus in the lab,” she explains, “we can better understand the ecological context in which various compounds are produced, and thus improve efforts to capitalize on a naturally occurring process."

Their research aims to uncover how bacteria use natural products to interact with each other and the environment. Puri elucidates the challenge: "We live in a time where we have virtually unlimited access to bacterial DNA (genome) sequences. But we have a hard time making sense of the vast majority of this information in the lab." To address this, the team grows bacteria in conditions closer to their natural environment, which has revealed exciting insights. Puri notes, "We can use relatively simple materials to uncover new bacterial behaviors in the lab in a reproducible manner."

The Puri-Beals collaboration has yielded significant findings, showing that bacterial behavior varies depending on their location within the model ecosystem. This research has potential applications in alternative energy, agriculture, and health by optimizing the use of microbes for various purposes. Their work not only advances our understanding of bacterial genetics but also paves the way for practical applications with far-reaching societal impacts.

As Puri emphasizes, "This work underscores that it is critical to think about the environment the bacterium of interest came from to understand what the genes in bacterial DNA are doing, since that is where they evolved." This approach promises to enhance our ability to harness microbes as sources for new natural products and to optimize their use in diverse applications.

Decoding Human Milk Oligosaccharides

In the aftermath of the 2022-2023 infant formula shortage, the research of Professor Gabe Nagy and graduate student Sanaz Habibi (they/their) has taken on newfound significance. Their project, focused on characterizing human milk oligosaccharides (HMOs), addresses crucial sugars in human milk that play a vital role in infant development.

Gabe Nagy and graduate student Sanaz Habibi

The complexity of HMOs presents a significant challenge, with potentially over 200 different compounds, yet authentic references are currently available for only about 30 of them. Nagy and Habibi are at the forefront of developing new analytical techniques to enhance HMO characterization, which could have profound implications for improving infant formula and understanding infant nutrition.

Habibi, who joined Nagy's lab in 2021, brings expertise in analytical chemistry and instrumentation from their undergraduate studies at Virginia Commonwealth University. Their research utilizes high-resolution cyclic ion mobility spectrometry-mass spectrometry (cIMS-MS) to analyze HMOs. Habibi explains their journey: "I became very interested in the cIMS-MS instrument that was being used in his lab, despite having little to no background in IMS or MS. I realized that Gabe's lab was the best fit for me to learn a different type of separation technique and increase my knowledge of mass spectrometry for studying an important class of carbohydrates."

Further elaborating on their innovative approach Nagy says, "We aim to develop advanced methods using ion mobility separations and mass spectrometry. These methods aim to decipher the structures of all possible HMOs, addressing the gap in understanding caused by the lack of comprehensive reference materials." This work involves constructing collision cross section databases, which provide numerical descriptions of the size, shape, and charge of ions—crucial for accurately identifying both known and unknown HMOs in real human milk samples.

The team's work is particularly timely, as Nagy points out: "The world of sugar analysis has lagged behind other fields by 10-20 years, and we believe that our lab could develop new tools in order to bridge this gap." The duo’s research not only contributes to solving immediate challenges in infant nutrition but also has broader implications for analytical chemistry.

Nagy and Habibi are optimistic about the wider applicability of their tools and methods. They envision their advancements being adopted by laboratories worldwide across various molecule classes. Habibi emphasizes the potential of their work "to enhance the comprehensive profiling of human milk using our developed methods."

This pioneering research has the potential to empower other disciplines such as biology and medicine by providing access to advanced analytical tools. As infant nutrition continues to be a critical area of study, the work of Nagy and Habibi stands at the forefront of efforts to improve our understanding and application of human milk components in infant formula and beyond.