The Mucus Core will perform key mucin biochemical and biophysical measurements for all the Projects of the tPPG, which as a group are devoted to developing effective treatments to enhance mucus clearance based on a solid understanding of the physical and biochemical forces and factors which affect mucus viscoelasticity, transport, and the adhesion of mucus to epithelial surfaces. Emerging data from the Sheehan/Kesimer laboratory indicate strongly that proteins associating tightly with mucins are essential to mucus viscoelasticity and participate in airways defense. For Projects II and III, accordingly, the Core will use mass spectrometry approaches to identify the proteins that associate intimately with mucins, the mucin-interacting proteome. The Mucus Core will offer the following services to the Projects: 1. Mucin concentrations in mucus or sputum samples submitted by all the Projects will be determined and the mucins identified. Complementary biophysical and biochemical quantitative techniques will be used for samples containing quantities of mucin in the ?g, sub-?g, and ng ranges, as specified below. Mucins will be identified by ELISA and/or agarose gel electrophoresis (aGE)/Western blotting. 2. Mucus rheology, i.e., its viscoelastic properties, will be determined for ]x sized samples sputum samples from Project III using a cone and plate rheometer. 3. The proteins comprising the mucin-interacting proteome will be identified by mass spectrometry for all three Projects, and the results from human vs. mouse and the different treatments analyzed differentially. 4. The effects of N-acetyl cysteine, and other reducing agents used in all the Projects will be determined for mucus rheology and mucin biochemistry. 5- Core C will provide purified mucin standards for testing the mucus reducing agents. 6- Measurement of mucus partial osmotic pressure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL108808-03
Application #
8686933
Study Section
Special Emphasis Panel (ZHL1-CSR-Q)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$397,690
Indirect Cost
$129,201
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Pandiyarajan, C K; Rubinstein, Michael; Genzer, Jan (2016) Surface-Anchored Poly(N-isopropylacrylamide) Orthogonal Gradient Networks. Macromolecules 49:5076-5083
Sesma, Juliana I; Weitzer, Clarissa D; Livraghi-Butrico, Alessandra et al. (2016) UDP-glucose promotes neutrophil recruitment in the lung. Purinergic Signal 12:627-635
Livraghi-Butrico, A; Grubb, B R; Wilkinson, K J et al. (2016) Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol :
Leuty, Gary M; Tsige, Mesfin; Grest, Gary S et al. (2016) Tension Amplification in Tethered Layers of Bottle-Brush Polymers. Macromolecules 49:1950-1960
Baeza, Guilhem P; Dessi, Claudia; Costanzo, Salvatore et al. (2016) Network dynamics in nanofilled polymers. Nat Commun 7:11368
Button, Brian; Anderson, Wayne H; Boucher, Richard C (2016) Mucus Hyperconcentration as a Unifying Aspect of the Chronic Bronchitic Phenotype. Ann Am Thorac Soc 13 Suppl 2:S156-62
Yu, Dongfang; Davis, Richard M; Aita, Megumi et al. (2016) Characterization of Rat Meibomian Gland Ion and Fluid Transport. Invest Ophthalmol Vis Sci 57:2328-43
Choueiri, Rachelle M; Galati, Elizabeth; Thérien-Aubin, Héloïse et al. (2016) Surface patterning of nanoparticles with polymer patches. Nature 538:79-83
Ramsey, Kathryn A; Rushton, Zachary L; Ehre, Camille (2016) Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins. J Vis Exp :
Bennett, William D; Henderson, Ashley G; Donaldson, Scott H (2016) Hydrator Therapies for Chronic Bronchitis. Lessons from Cystic Fibrosis. Ann Am Thorac Soc 13 Suppl 2:S186-90

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