Centuries of Questions; Finally, Some Answers

Modern mass spectrometers allow researchers to probe the contents of individual cells, helping us find what we've missed in biochemistry.

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“My big idea is to figure out what we’ve missed in biochemistry.”

Amy Caudy, professor of molecular genetics at the University of Toronto, is studying biology using technology that’s been around for hundreds of years; mass spectrometry measures the weight-to-charge ratio of individual ionized molecules, helping researchers identify what’s in a sample. But what makes it especially relevant today is that it’s more sensitive and powerful than ever.

“This space is so exciting because we are at a moment of new technology coming to bear on an old problem,” says Caudy.

“Now, with the advent of high-resolution mass spectrometry, we can bring a whole new method to bear on these questions and measure things that were absolutely impossible to measure before.”

Modern mass spectrometers can easily distinguish molecules that differ by just a proton or neutron — the particles that make up the cores of atoms — meaning that researchers can tell molecules apart even when they’re highly related.

The increased sensitivity means that biochemists are now beginning to be able to probe the contents of individual cells; it was previously only possible to assess large populations of cells. That restriction used to mean a lot of missed insights.

“Knowing what happens in one cell is so important because many diseases, like tumours, start from just one or a few cells that have gone wrong,” adds Caudy. “And if you could target those particular cells then you could stop the growth of the entire tumour.”

Caudy’s work also extends into mysteries beyond medicine. One of them is how worms are able to breathe underwater. Oxygen levels in water are low compared to those in air, and worms share underwater environments with microbes that are also consuming oxygen. That means that worms often find themselves without enough oxygen to live.

“It turns out that parasitic worms, and other kinds of worms out in the environment, they don’t need oxygen to breathe,” says Caudy. “How they made the special molecule to do that wasn’t known, and we’ve pretty much figured it out.”

Despite looking at similar problems for hundreds of years, there is still so much to learn by refining old tools to probe deeper into old mysteries. From health and medicine to natural curiosities, having a single-cell and molecular-level understanding of biochemistry will help us see more of what we’ve been missing.

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Amy Caudy is the Canada Research Chair in Metabolomics for Enzyme Discovery, and an Associate Professor at the University of Toronto in the Donnelly Centre for Cellular and Biomolecular Research and in the Department of Molecular Genetics. Caudy earned her PhD from the Watson School of Biological Sciences at Cold Spring Harbor Laboratory, working with Gregory Hannon identifying protein components of the RNAi complex RISC and developing the first vectors for stable RNA interference (RNAi) in mammalian cells. Caudy then joined John Atkinson’s laboratory at Washington University School of Medicine to T regulatory cells as a Ruth Kirchstein NRSA Postdoctoral Fellow. In 2005, she became a Lewis-Sigler Fellow at the Lewis-Sigler Institute for Integrative Genomics at Princeton University. There, she turned to the study of metabolism. The focus of her laboratory is the discovery of novel metabolic pathways.  Her group has identified more than two dozen likely new enzymes in the model eukaryote yeast, including the discovery of a new pathway that produces the DNA precursor ribose. She is a founding organizer of the Cold Spring Harbor summer course in metabolomics, and has collaborated with Agilent Technologies to develop a widely disseminated method for mass spectrometric analysis of metabolites.

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