SBIR Phase II: Development of a Eukaryotic Membrane Protein Overexpression System

这个小型企业创新研究（SBIR）第二阶段项目集中于为真核细胞膜蛋白创造一种新颖，经济和强大的生产技术，这是一组仍然难以处理但具有巨大医学和科学重要性的蛋白质。大多数膜蛋白很难以任何显著的量获得，即使在毫克级，因为它们的天然生物合成水平通常非常低，并且目前可用的生产方法对膜蛋白无效。该研究项目将利用一种通用且易于培养的微生物，该微生物可以在一定条件下产生增殖膜来宿主重组膜蛋白。通过活性分析和直接蛋白质分离，评估各种策略的有效性。该技术的更广泛影响是在几乎所有治疗领域，包括传染病、癌症、膜蛋白遗传缺陷引起的遗传疾病、中枢神经系统疾病、心血管系统疾病、消化系统疾病和许多其他疾病，开发新一代有效药物。这项技术对科学、医学和社会的影响将是非常重大的。该技术可用于大量生产非常大量的膜蛋白，特别是表面膜蛋白，用于基于结构的药物设计、蛋白质工程、蛋白质治疗以及用于开发针对感染性疾病和癌症的诊断和疫苗。这些努力不仅将为非常难以研究的膜蛋白提供新的科学认识，而且最终将改变目前人类疾病诊断和治疗的现状。

This Small Business Innovation Research (SBIR) Phase II project concentrates on creating a novel, economical and powerful production technology for eukaryotic membrane proteins, a group of proteins that remain intractable yet are of tremendous medical and scientific importance. A majority of membrane proteins are very difficult to obtain in any significant quantities, even at milligrams scale since their natural biosynthesis levels often are very low and currently available production methods are not effective for membrane proteins. This research project will utilize a versatile and easy-to-cultivate microorganism that can generate proliferated membranes under certain conditions to host the recombinant membrane proteins. The efficiency of various strategies will be evaluated through activity assays and direct protein isolation.The broader impact of the technology are new generations of efficacious medicines in virtually all therapeutic areas including infectious diseases, cancer, genetic diseases due to genetic defect in membrane proteins, central nervous system diseases, cardiovascular system diseases, digestive system diseases and many others. The impact of this technology in science, in medicine and in society will be very significant. The technology can be utilized to mass-produce a very large number of membrane proteins, especially surface membrane proteins for applications in structure-based drug design, in protein engineering, in protein therapeutics, and for the development of diagnostics and vaccines against infectious diseases and cancer. These efforts will not only provide new scientific understandings of very difficult-to-study membrane proteins but also eventually transform the current landscape of diagnostics and therapeutics for human diseases and illnesses.