Core D: Mucus Biochemistry/Biophysics Core

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The mucosal surfaces of the respiratory, gastrointestinal, and reproductive systems are continually exposed to the exterior environment. In health, the continual clearance of a luminal mucus layer in these organ systems represents a key component of innate defense against disease. However, in people with cystic fibrosis (pwCF), abnormal mucus clearance represents a key contributor to disease pathogenesis. Over the last decade, our studies have revealed that CFTR dysfunction in pwCF leads to epithelial surface layer volume depletion and, thus, “dehydration” of the overlying mucus layer. This increased mucus concentration, coupled with disease-related mucin overproduction, results in mucus adhesion to epithelial surfaces and mucostasis. It is likely that adhesion of the mucus to the epithelial surface represents an initiating event in the pathogenesis of the CF in both the lung and gut. Static mucus constitutes the nidus for the persistent bacterial infection that provokes an ineffective inflammatory response in the airways and likely small intestine (i.e., small bowel overgrowth). Given the importance of understanding the role that mucus and mucins play in CF pathogenesis in both the GI system and lungs, the goal of the Mucus Biochemical and Biophysical Core (Core D) is to provide both internal and external researchers access to a unique spectrum of tools and reagents necessary for understanding the biochemical and biophysical properties of mucus/mucins in health and pwCF. To this end, Core D laboratories offer a series of novel techniques developed to directly measure key mucus biochemical and biophysical properties, including mucin concentration, osmotic pressure, adhesion strength, cell surface frictional interactions, and viscous and elastic moduli. Collectively, these measurements will facilitate an understanding of how abnormal mucus in CF produces adherent, static, mucus and to identify optimal combinations of pharmacological agent(s) to restore/accelerate the rate of mucus transport in people with CF. The main goal of the UNC Mucus Biochemistry and Biophysics Core is to provide investigators data from these specialized mucus/mucin assays that are either not possible or feasible in their labs. Core D is uniquely positioned to: 1) investigate the properties of user supplied mucus samples; and 2) assess the impact of therapeutic agents, supplied by investigators, to reduce mucus accumulation and accelerate mucus clearance. A strength of this Core is the collaboration of a group of scientists who are experts in the field of mucus/mucin analysis. The benefit to potential Core users is the ability to generate data utilizing our novel techniques, freeing individual investigators to focus on basic science, and drug development.