Investigating Membrane Proteins with Magnetic Resonance Spectroscopy

利用这一奖项，化学学部的生命过程化学项目资助了迈阿密大学化学与生物化学系的Gary a . Lorigan教授，以研究一种被称为pinholin的膜蛋白的结构和动态特性。pinholin是一种重要的膜结合蛋白，直接参与细胞死亡。病毒感染周期的最后一步是细胞通过裂解死亡，即细胞膜的破裂。Lorigan教授计划开发实验程序，以表征膜中针孔蛋白的活性和非活性形式的结构和机制。追求允许研究生，本科生和来自代表性不足群体的学生获得尖端电子顺磁共振（EPR）生物物理技术的专业培训。这些新的生物物理方法对于研究各种不同的膜蛋白系统是有用的。该研究项目还促进了迈阿密大学名为DUOS的变革性STEM指导计划的发展，该计划加强了研究生和本科生研究人员之间的协同作用/互动，以便在博士学位授予部门的一名教师的监督下进行研究项目的合作。Lorigan实验室的一个本科生/研究生团队计划参加这个新项目。该研究项目的目的是表征活性和非活性pinholin的结构、拓扑、动力学和寡聚化状态。强大的CW-EPR和脉冲EPR光谱技术被用于研究针孔蛋白的不同形态。要测量自旋标签之间的多个距离，以提供嵌入在膜中的针孔蛋白的重要结构信息。本研究结果将为pinholin机制和细胞裂解提供新的认识，并为膜蛋白的研究提供新的方法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor Gary A. Lorigan from the Department of Chemistry and Biochemistry at Miami University to investigate the structural and dynamic properties of a membrane protein known as pinholin. Novel powerful state-of-the-art techniques are used to study pinholin, which is an important membrane-bound protein that is directly involved in cell death. The last step of the virus infection cycle is cell death through lysis, the breakdown of the cell membrane. Professor Lorigan plan to develop the experimental procedures to characterize the structure and mechanism of the active and inactive forms of pinholin in a membrane. The pursuit allows graduate students, undergraduate students, and students from under-represented groups to obtain specialized training in cutting-edge Electron Paramagnetic Resonance (EPR) biophysical techniques. The new biophysical methods developed are useful generally to study a variety of different membrane protein systems. This research project also enables the development of a transformative STEM mentoring program called DUOS at Miami University that strengthens the synergy/interaction between graduate and undergraduate researchers to collaborate on a research project under the supervision of a faculty member in a Ph.D. granting department. One undergraduate/graduate student team from the Lorigan lab is scheduled to participate in this new program.The research project is conducted to characterize the structure, topology, dynamics, and oligomerization state of the active and inactive forms of pinholin. Powerful CW-EPR and pulsed EPR spectroscopic techniques are used to investigate the different formations of pinholin. Multiple distances are to be measured between spin labels to provide important structural information on the pinholin embedded in a membrane. Information from this study should provide new insight into the pinholin mechanism and cell lysis, and provide novel methodology generally applicable to membrane proteins.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.