Protein purification by selective coacervation

蛋白质药物在治疗糖尿病、白血病、血友病、阿尔茨海默病和戈谢病以及骨质疏松症方面很重要。它们也是器官替代、组织再生和伤口修复的重要治疗剂，无论是由疾病、衰老还是战斗相关损伤引起的。生产这些药物所需的大规模蛋白质分离技术已经落后于分子生物学，现在它们的大部分成本都是由这些技术造成的。研究了使用公认安全（GRAS）聚合物（聚电解质）从形成靶蛋白的细胞粉碎物或裂解物中分离和浓缩靶蛋白。发生这种情况的过程是自发分离成两种液体：较致密的阶段含有高浓度的聚合物和目标蛋白质。这项工作的目标是了解这种复杂凝聚的原理，通过(a)聚合物的选择，(b)影响凝聚的条件的选择，以及(c)从目标蛋白中去除聚合物的方法来优化这种凝聚。生物工程、生物分析和高分子物理化学的跨学科结合为该领域的发展提供了一个统一观点的例子。pi在让代表性不足的群体成员参与研究方面发挥了积极的作用。性别和种族上的少数群体在他们的群体中都占很大比例。目前两组共有9名女性（1名博士后，4名研究生，3名本科生，1名高中毕业生），其中3人参与了与本提案（蛋白质聚电解质凝聚）相关的工作。积极参与NSF REU和IGERT资助，以促进本科研究。参与该项目的学生将获得在生物技术和制药创新与应用领域非常重要的培训。

Protein drugs are important in the treatment of diabetes, leukemia, hemophilia, Alzheimer's and Gaucher disease, and osteoporosis. They are also important therapeutic agents in organ replacement, tissue regeneration and wound repair, regardless of whether resulting from disease, aging or battle related injury. The technologies for large scale protein separation needed to produce these drugs have lagged behind molecular biology, and now are responsible for most of their cost. The use of generally recognized as safe (GRAS) polymers (polyelectrolytes) are investigated to isolate and concentrate the target proteins from the cell crush or lysate in which they are formed. The process by which this happens is a spontaneous separation into two liquids: the more dense phase contains the polymer and the target protein in high concentration. The goal of this work is to understand the principles by which this complex coacervation can be optimized by (a) the selection of the polymer, (b) the choice of the conditions for effecting the coacervation, and (c) the method of removing polymer from the target protein.The interdisciplinary coupling of bioengineering, bioanlytical, and polymer physical chemistry proposed provide an example of the unification of perspectives appropriate to progress in this field. The PIs take a pro-active role in involving members of underrepresented groups in research. Both gender and racial minorities make up a significant proportion of their groups. There are currently nine women in the two groups (1 postdoc, 4 graduates, 3 undergraduates, 1 high school senior), three of whom are involved in work related to this proposal (protein polyelectrolyte coacervation). There is active participation in an NSF REU and IGERT grants for promoting undergraduate research. Students working on this project will obtain training in areas of great importance to biotechnology and pharmaceutical innovation and applications.