Mucus is an ancient glycoconjugate-rich gel found at all biological size scales from e-coli to humans that serves as the mediator between the organism surface and the outside world. In the human system, every tract, gland, pore and interfacial barrier is coated with glycoconjugate gels tuned to their protective needs. In the lung, incoming particles, pathogens and a variety of toxins are absorbed into a bed of mucus on the upper airway surface which is transported to the esophagus where it is taken to the GI tract. This ability of mucus to flow is the key element of the mucus clearance process. Therefore rheological properties of mucin, such as its viscosity and elasticity at different shear rates play an important role in the detailed balance of the airway surface liquid transport. Recent experiments have shown that there is no simple relationship between mucus rheology and successful mucus transport. Dilution experiments performed on human lung cell cultures have shown that when the mucus is too ‘dilute’ the transport is ineffective and when the mucus is too ‘thick’ transport is stopped. We must hypothesize that the rheological properties of the secreted respiratory mucus gel are actively tuned to optimise its coupling to cilia. These observations have not been related to specific rheological properties or at a deeper level of structure to macromolecular concentration or properties, composition and molecular interactions. Simply, there is no reliable molecular model of mucin rheology. The objective of Project 1 is to develop such model through the identification of the key parameters that connect mucus composition to the rheological properties that permit successful mucus flow.