Grant: Discovery Grants Program - Individual

Lung surfactant, a surface active material (SAM), coats the aqueous lining of the lung air-sacs and tubes. This helps us breathe normally. SAM is a soapy, fattish, membranous material containing lipids and proteins. Lack of sufficient SAM in a baby's lung leads to potentially fatal respiratory distress syndrome (RDS).  Dysfunctions of SAM in adults lead to acute-RDS (ARDS), and is related to other diseases such as asthma, cystic fibrosis and pneumonia. ARDS occurs due to leakage of specific materials from blood (serum constituents) into the lung air-sacs. This program will examine how models of SAM are inhibited or affected by serum and its specific constituents.     We will use a set of state-of-the-art biophysical tools for our studies. These are mainly the capillary- and captive-bubble surfactometer, atomic force microscopy as well as NMR & infrared/Raman micro-spectroscopy. These complementary methods will allow us to decipher how the physical, chemical and structural properties of SAM change under the influence of serum materials. A clinically used surfactant developed in Canada to treat RDS patients (Bovine Lipid Extract Surfactant or BLES) will be utilized. Selected amounts and types of serum materials, such as albumin (as found in blood and in egg-white), fibrinogen and lipoprotein-cholesterol will be mixed with BLES and studied. The resulting structure-function changes in BLES as observed in the laboratory will suggest possible molecular mechanisms for how SAM becomes dysfunctional in the lung. The program will help in the development of artificial SAM, as well as in our fundamental understanding of complex membranous systems. It is anticipated that using several complimentary methods and collaborative studies will generate information that can develop better treatment strategies for lung diseases, as well as further insight into the biophysical and molecular basis of the diseases.