CAREER: Measuring the Structural Transitions of Electrosprayed Proteins

在化学系化学测量和成像计划的支持下，印第安纳大学-普渡大学印第安纳波利斯分校的Ian Webb和他的团队正在开发方法，以研究蛋白质从液态转变为气相时其结构是如何变化的。这项工作很重要，因为它有可能显著增加对蛋白质结构以及它在电喷雾电离(ESI)过程中如何变化的理解。这些研究有可能阐明蛋白质的哪些特定区域负责气相中的压缩和膨胀。通过与工业伙伴的互动，研究成果将传播到其他实验室，这将增加方法的影响，并有助于推进生物分子结构分析的现有基础设施。居住在印第安纳波利斯儿童博物馆附近的个人和家庭将受益于这项旨在扩大对STEM的接触的教育计划。利用质谱学研究蛋白质和蛋白质复合体的结构是很普遍的。然而，蛋白质在多大程度上保持其天然结构在质谱计中仍存在争议。这项拟议的研究将使用质谱学工具来直接确定在使用化学探针进行质谱分析时天然折叠蛋白质的结构变化。拟议项目的成功实施将使人们更好地了解在溶液、气相或在溶液和气相之间的转变过程中稳定或不稳定的侧链化学和结构基序。这项研究还包括一项综合教育计划，目标是在印第安纳波利斯儿童博物馆为当地印第安纳波利斯社区6-12岁的儿童、家长/监护人和教育工作者带来令人兴奋和信息丰富的STEM学习体验。儿童博物馆的城市位置、对居住在周围六个社区内的个人和家庭的免费入场以及许多STEM学习资源吸引了不同的参观者群体，这些社区中历史上被排斥的家庭对STEM的兴趣具有巨大的潜力。韦伯实验室和儿童博物馆之间的这种合作关系将使化学测量更容易获得，允许来自历史上被排除在外的群体的个人直接参与STEM实验。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Ian Webb and his group at Indiana University-Purdue University Indianapolis are developing methods to investigate how proteins change their structure as they transition from liquid phase to gas phase. This work is important as it has the potential to significantly increase the understanding of protein structure and how it changes during electrospray ionization (ESI). The studies have the potential to illuminate which specific regions of proteins are responsible for compaction and expansion in the gas phase. Through interaction with industrial partners, research results are to be disseminated to other laboratories which will increase the impact of the methods and contribute to the advancement of available infrastructure for biomolecular structural analysis. Individuals and families living near the Children's Museum of Indianapolis will benefit from the education plan which aims to broaden exposure to STEM. The use of mass spectrometry to study structures of proteins and protein complexes is widespread. However, the extent which proteins keep their native structures inside a mass spectrometer is under debate. This proposed research will use mass spectrometric tools to directly determine the changes in structure to natively folded proteins during mass spectrometric analyses with chemical probes. Successful implementation of the proposed project will lead to a greater understanding of the side chain chemistries and structural motifs that are either stabilized or destabilized in solution, the gas phase, or in the transition between solution and gas phase. This research also includes an integrated educational plan with the goal of bringing a structural mass spectrometry experiments to local Indianapolis community children ages 6-12, parents/guardians, and educators in an exciting and informative STEM learning experience at the Children’s Museum of Indianapolis. The Children’s Museum’s urban location, free admission to individuals and families living within six surrounding neighborhoods, and many STEM learning resources attract a diverse group of attendees, with great potential to increase interest in STEM from historically excluded families in these communities. This partnership between the Webb laboratory and the Children’s Museum will make chemical measurements more accessible, allowing individuals from historically excluded groups to participate directly in STEM experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.