Na+ TRANSPORT INHIBITION BY RESPIRATORY SYNCYTIAL VIRUS

呼吸道合胞病毒对 Na 转运的抑制

• 批准号: 7110384
• 负责人: IAN CHRISTOPHER DAVIS
• 金额: $ 12.01万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110384
• 关键词: A549; Alveolar; Amiloride; Anatomy; Animal Model; Animals; Apoptosis; Biochemical; Bronchiolitis; Cell physiology; Cell surface; Cells; Child; Clinical; Cytopathology; Development; Doctor of Philosophy; Electrophysiology (science); Ensure; Environment; Epithelial; Epithelial Cells; Human; Hypoxemia; In Situ Hybridization; In Vitro; Inbred BALB C Mice; Infection; Ion Channel; Ion Transport; Ions; Knowledge; Laboratory Animal Medicine; Laboratory Animals; Liquid substance; Lower respiratory tract structure; Lung; Marines; Measurement; Measures; Mediating; Mentors; Mining; Mus; Necrosis; Northern Blotting; Nose; Patch-Clamp Techniques; Pathogenesis; Pathology; Pathway interactions; Physiology; Property; Protein Subunits; Proteins; Research; Respiratory Syncytial Virus Infections; Respiratory Tract Diseases; Respiratory physiology; Respiratory syncytial virus; Reverse Transcriptase Polymerase Chain Reaction; Ribavirin; Role; Scientist; Seminal; Structure of respiratory epithelium; Techniques; Testing; Trachea; Training; Ubiquitin; Universities; Upper respiratory tract; Viral; Viral Pathogenesis; Virus; Western Blotting; alveolar epithelium; comparative; epithelial Na+ channel; in vitro Model; in vivo; monolayer; multicatalytic endopeptidase complex; patch clamp; protein expression; respiratory; respiratory virus; stoichiometry; veterinary science

CANDIDATE: I graduated from the University of Bristol in 1992, with Honours in Anatomical Science and Veterinary Science. At UAB I received training in laboratory animal medicine, laboratory animal pathology, and viral pathogenesis in animal models (Ph.D. February 2000; mentor Dr. Patricia Fultz). Subsequently, I elected to join Dr. Matalon's research group, where I might build on my knowledge of viral pathogenesis by cross-mining in electrophysiology, and apply these techniques to study the pathogenesis of human respiratory viral pneumonitides. RESEARCH: Respiratory syncytial virus (RSV) is commonest cause of lower respiratory tract disease in children worldwide. Pathogenesis of RSV-induced bronchiolitis is poorly understood, and effects of RSV infection on ion transport (a seminal function of respiratory epithelial cells) have not been investigated. I hypothesize that RSV infection of respiratory epithelial cells reduces their Na ? transport capacity. Preliminary studies have demonstrated that this hypothesis is correct, both in vitro and in RSV-infeeted BALB/c mice. My aims for years 01- 03 are to: (1) quantify alterations in Na + transport across airway and alveolar epithelia in vivo and ex vivo, after infection of BALB/c mice with RSV; (2) define changes in Na + currents and amiloride-sensitive channel activity after RSV infection of murine epithelial cells in vitro; and (3) correlate alterations in Na + transport induced by RSV in vitro and in vivo with alterations in ENaC expression by marine respiratory epithelia. My plan for years 04-05 is to determine the role of the ubiquitin/proteasome pathway in mediating reduced Na+ transport after RSV infection of respiratory epithelia, and to identify the role of the RSV small hydrophobic (SH) gene product in modulation of Na + transport. I will use a combined electrophysiologic and biochemical approach to investigate effects of RSV on Na + transport at all levels, from the single cell to the whole animal, and to correlate these effects to Na + channel expression and degradation. My project will emphasize cross-training in diverse techniques, including short-circuit measurements across monolayers, radioisotopic ion flux studies, whole cell and single channel patch-clamp, and measurement of alveolar fluid clearance and nasal potential difference in mice. ENVIRONMENT: This SERCA, with Dr. Matalon (lung physiology) as mentor and Dr. Sullender (respiratory syncytial virus) as co-mentor, will provide the training and setting I require for my maturation into an independent scientist focused on comparative pathophysiologic effects of respiratory viruses on normal epithelial cell function.

我1992年毕业于布里斯托尔大学，获得了解剖学和兽医学的荣誉学位。在UAB，我接受了实验动物医学、实验动物病理学和动物模型病毒发病机制的培训（2000年2月博士学位，导师Patricia Fultz博士）。随后，我选择加入Matalon博士的研究小组，在那里我可以通过交叉挖掘电生理学对病毒发病机制的了解，并将这些技术应用于研究人类呼吸道病毒性肺炎的发病机制。