This application requests support to provide a substantial increase in the principal investigator's protected time for research on pulmonary surfactant. The principal investigator (PI) brings to his research a combination of solid training in both physical science and clinical medicine, including a doctorate in biophysical chemistry and a fellowship in pulmonary and critical care medicine. He is currently an assistant professor with extensive clinical, teaching, and administrative responsibilities in addition to his research. He now has eight years of experience in research concerning pulmonary surfactant, including four years as an independent investigator in his own laboratory. These studies have been supported by several grants designed for starting investigators. He currently is PI or co-PI on three peer-reviewed nationally competitive grants, including two from the Whitaker Foundation and a recent First Award from NIH. His research focuses on two critical steps essential for surfactant function. The studies proposed in this application will examine mechanisms by which pulmonary surfactant adsorbs rapidly to form interfacial films. A second project concerns structures within the surface films allow them to remain stable at the interface during compression to very low surface tensions. A manuscript concerning preliminary findings is approaching submission, and specific aims are being formulated for an application to provide grant support. The PI's research emphasizes collaboration with other laboratories which provide access to state-of-the- art methods in interfacial science which have not previously been used to study pulmonary surfactant. The ultimate goal of the PI's research is to extend the successful use of surfactant in neonates to adult patients, and in particular to develop inexpensive effective surfactant to i=minimize the cost of the larger doses required in adults. The funds provided by this grant would increase the PI's commitment to research from 45% to 83%. His only other obligations would be 1-2 seminars and 102 lectures per year on subjects directly relate to his research, and 8 weeks of clinical responsibility which he has requested to maintain his clinical skills. The research proposal is the project funded by a First Award which began one month prior to the submission of the application. The proposed studies will establish mechanisms by which pulmonary surfactant adsorbs rapidly to an air-liquid interface to form interfacial films capable of reducing surface tension during compression.
| Rugonyi, Sandra; Biswas, Samares C; Hall, Stephen B (2008) The biophysical function of pulmonary surfactant. Respir Physiol Neurobiol 163:244-55 |
| Schram, Vincent; Hall, Stephen B (2004) SP-B and SP-C alter diffusion in bilayers of pulmonary surfactant. Biophys J 86:3734-43 |
| Smith, Ethan C; Laderas, Ted G; Crane, Jonathan M et al. (2004) Persistence of metastability after expansion of a supercompressed fluid monolayer. Langmuir 20:4945-53 |
| Schram, Vincent; Anyan, Walter R; Hall, Stephen B (2003) Non-cooperative effects of lung surfactant proteins on early adsorption to an air/water interface. Biochim Biophys Acta 1616:165-73 |
| Schief, William R; Antia, Meher; Discher, Bohdana M et al. (2003) Liquid-crystalline collapse of pulmonary surfactant monolayers. Biophys J 84:3792-806 |
| Smith, Ethan C; Crane, Jonathan M; Laderas, Ted G et al. (2003) Metastability of a supercompressed fluid monolayer. Biophys J 85:3048-57 |
| Piknova, Barbora; Schram, Vincent; Hall, Stephen B (2002) Pulmonary surfactant: phase behavior and function. Curr Opin Struct Biol 12:487-94 |
| Discher, Bohdana M; Maloney, Kevin M; Grainger, David W et al. (2002) Effect of neutral lipids on coexisting phases in monolayers of pulmonary surfactant. Biophys Chem 101-102:333-45 |
| Schram, V; Hall, S B (2001) Thermodynamic effects of the hydrophobic surfactant proteins on the early adsorption of pulmonary surfactant. Biophys J 81:1536-46 |
| Piknova, B; Schief, W R; Vogel, V et al. (2001) Discrepancy between phase behavior of lung surfactant phospholipids and the classical model of surfactant function. Biophys J 81:2172-80 |
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