The Sticky Science of Mucus: Biopolymer Networks, Clearance, and Therapeutic Frontiers

Abstract:

While most of us think of mucus as a nuisance, this talk will hopefully convince you that it's one of the body's most sophisticated defense systems. This remarkable gel-like material is critical to trap invading pathogens and other harmful particles. At the heart of this system are mucins, the massive glycoprotein polymers that give mucus its unique gel-like properties. When mucins and mucus go awry, the results are catastrophic: muco-obstructive lung diseases like cystic fibrosis and COPD affect tens of millions of people worldwide, robbing them of the ability to breathe freely. My talk will take you on a journey through the biology of mucus, from the molecular machinery that builds it to the physical forces that move it. We will tackle one of the field's most fascinating puzzles: why are mucins among the longest biopolymers ever discovered, and what does that extraordinary size mean for how they function? We will also explore the underappreciated world of cell surface-tethered mucins, which coat the airway epithelium and serve as a front-line defense against the outside world. Zooming out to the whole lung, we will investigate how mucus is normally swept out of the airway and what happens when that system breaks down. This will span defects in cilia and cough clearance that allow mucus to accumulate and infections to take hold and survey the most promising therapeutic strategies on the horizon. I will also present our recent studies on an unrecognized mechanism of mucus clearance, called gas-liquid transport, in which normal breathing itself drives mucus out of the lung. This finding reframes our understanding of airway biology and hints at entirely new ways to treat lung disease.

Short bio

Dr. Brian Button is a Professor of Biochemistry & Biophysics at the University of North Carolina at Chapel Hill, with joint appointments in the Microbiology and Immunology Department and the UNC-NC State Biomedical Engineering Department. He is a member of the Marsico Lung Institute and UNC Cystic Fibrosis Center, where his research focuses on the biochemical and biophysical properties of airway mucus and the mechanisms that govern its clearance in health and disease. His work spans from the molecular biology of mucins to whole-lung physiology, with a particular emphasis on understanding how mucus clearance breaks down in muco-obstructive diseases such as cystic fibrosis and chronic bronchitis. Dr. Button's laboratory develops novel experimental and therapeutic strategies aimed at restoring airway defense in patients with these debilitating lung diseases.

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