Novel Physical Methods for Determining Membrane Protein Dynamics and Kinetics

描述（由申请人提供）： 项目总结和培训目标 我对膜蛋白之间的动态结合相互作用感兴趣。它们是如何相互作用的，它们结合和解除结合的紧密程度和速度有多快？这些相互作用如何影响蛋白质功能？我建议开发新的技术来回答这些问题，包括一种新的方法来测量结合/解结合率，和一种新的研究工具，称为“仿生内质网”。“这些新技术的发展将需要一段时间的密集培训，在生物医学工程和动力学。这种额外的培训将大大提高我的职业生涯作为一个独立的研究科学家的专业准备。 与公共卫生的相关性 这个研究项目的目标是重要的，无论是在直接研究的模型蛋白质，并在膜蛋白研究的一般建议的技术进步。SERCA泵的紊乱及其受磷蛋白的调节与疾病相关，包括心力衰竭。通过了解这些蛋白质如何工作，我们可能会开发药物或其他临床疗法来干预疾病过程。此外，我提出的技术发展可能普遍适用于许多其他临床重要的膜蛋白的研究。

DESCRIPTION (provided by applicant): Project Summary and Training Goals I am interested in the dynamic binding interactions between membrane proteins. How do they interact, and how tightly and rapidly do they bind and unbind? How do these interactions affect protein function? I propose to develop new techniques to answer these questions, including a new way to measure binding/unbinding rates, and a new research tool called a "biomimetic endoplasmic reticulum." Development of these new technologies will require an intensive period of training in biomedical engineering and kinetics. This additional training will greatly enhance my professional preparation for a career as an independent research scientist. Relevance to Public Health The goals of this research project are important, both in terms of the model proteins studied directly, and in terms of the proposed technical advancement of the study of membrane proteins generally. Disorders of the SERCA pump and its regulation by phospholamban have been correlated to disease, including heart failure. By understanding how these proteins work we might develop drugs or other clinical therapies to intervene in the disease process. Furthermore, the technical developments I propose are likely to be generally applicable to the study of many other clinically important membrane proteins.