Novel Physical Methods for Determining Membrane Protein Dynamics and Kinetics

描述(由申请人提供)： 项目摘要和培训目标 我对膜蛋白之间的动态结合作用感兴趣。它们如何交互，以及它们绑定和解除绑定的紧密程度和速度有多快？这些相互作用是如何影响蛋白质功能的？我建议开发新的技术来回答这些问题，包括一种测量结合/解结率的新方法，以及一种名为“仿生内质网”的新研究工具。开发这些新技术将需要在生物医学工程和动力学方面进行一段时间的密集培训。这次额外的培训将极大地增强我作为一名独立研究科学家职业生涯的专业准备。 与公共卫生的相关性 这一研究项目的目标是重要的，无论是就直接研究的模型蛋白质而言，还是就一般膜蛋白研究的拟议技术进步而言。SERCA泵的紊乱和磷蛋白对其的调节与包括心力衰竭在内的疾病有关。通过了解这些蛋白质是如何工作的，我们可能会开发药物或其他临床疗法来干预疾病的过程。此外，我提出的技术发展很可能普遍适用于许多其他临床上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.