VIRUSES: FROM PARTICLES TO PROTEOMICS

病毒：从粒子到蛋白质组学

• 批准号: 7960527
• 负责人: BRIAN P BOTHNER
• 金额: $ 11.18万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960527
• 关键词: Antiviral Agents; Apoptotic; Atomic Force Microscopy; Biology; Canine Parvovirus; Capsid; Caspase; Cells; Cessation of life; Complex; Computer Retrieval of Information on Scientific Projects Database; Cysteine Protease; Dependovirus; Emerging Communicable Diseases; Equilibrium; Frequencies; Funding; Grant; Hepatitis B Virus; Infection; Institution; Investigation; Knowledge; Measurement; Molecular Conformation; Motion; Mus; Norovirus; Parvovirus; Phase; Process; Property; Protein Dynamics; Proteins; Proteomics; Publications; Quartz; Research; Research Personnel; Resolution; Resources; Solutions; Source; System; United States National Institutes of Health; Virion; Virus; Virus Diseases; Work; base; cowpea chlorotic mottle virus; novel; pathogen; protein function; three dimensional structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The solution-phase protein motion that is part of a multi-component complex is rarely obvious from the high resolution three-dimensional structure. Protein function is intimately connected to dynamics and therefore knowledge of the frequency, range, and coordination of motion by supramolecular complexes is critical to understanding how they function. In this project, viruses are a paradigm for studying protein dynamics in supramolecular complexes. In the past year, significant steps have been made in the studies on the biophysical properties of virus particles. Systems currently under investigation include Hepatitis B virus, Adeno-associated virus, Canine Parvovirus, Cowpea Chlorotic Mottle Virus. A recent publication on Hepatitis B virus presents the first measurements of the rates and equilibria for protein motion in a megadalton complex. Breakthroughs have also been made in understanding how pH levels relevant to cell entry modulate the stability and dynamics of parvoviruses. Through the use of a quartz crystal microbalance and atomic force microscopy, the viscoelastic properties of a virus capsid in different conformation have been determined. Viruses are obligate cellular pathogens and therefore many cellular proteins are critical for viral infection, replication, and release from a host cell. Using proteomics-based approaches, Dr. Bothner is seeking to identify cellular proteins that are hijacked by viruses during the infection process. The significance of this work is two fold; the basic biology of viruses can be elucidated and novel targets for antiviral agents will be identified. Dr. Bothner's work on murine norovirus infection of mouse RAW cells has led to the identification of cysteine proteases upstream of the mitochorndria, which are involved in infection. Surprisingly, inhibition of caspases in general during infection leads to rapid, non-apoptotic death.

这个子项目是众多研究子项目之一