Emergent Protein Assemblies in Cytoplasm

蛋白质是细胞内的工作马，参与细胞功能的各个方面。它们通过相互作用促进的高阶组装的形成来发挥作用。它们的功能之一是新陈代谢。这是一个蛋白酶共同将碳水化合物等大营养素分解为较小分子的过程，将它们转化为生物燃料或细胞中其他生物质的构建块。 本项目将研究这些酶如何组装成复合物，调节或受代谢调节。从该项目中学到的知识将对有利于生物经济的生物燃料或生物质的有效生产产生深远的影响。该项目将通过与西北太平洋路易斯-斯托克斯少数民族参与联盟（PNW LSAMP）的合作，积极招募社区学院的转学生和续读生参加西雅图的华盛顿大学（UW）的研究。UW的转学生和继续就读的本科生主要来自科学，技术，工程和数学（STEM）中历史上代表性不足的边缘化（URM）群体。该项目的更广泛影响将加强STEM高等教育的转学生和继续学生的保留，并增加URM学生进入研究生课程的人数。该项目的目标是建立可测试的蛋白质组装模型，以响应细胞中的代谢变化。连续蛋白酶在活细胞内的代谢途径中形成瞬时超分子组装体或代谢子。我们将阐明负责它们组装成空间网络的物理机制，以及这些复合物如何通过计算机模拟调节代谢或被代谢调节。这项工作将建立在一个先进的理论框架，以表征在拥挤的，开放的多组分系统中分子簇的快速形成和分解，从实验数据和蛋白质结构模型中学习定量变量。预期的结果将提供新的机会，开发经验验证的假设来自复杂的分子模型作为生物标志物来预测细胞的代谢状态。该研究项目的长期目标与NSF的十大理念之一“理解生命的规则”相一致。该奖项反映了NSF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。

Proteins are the work horses inside a cell by participating all aspects of cellular function. They function through the formation of higher-order assemblies facilitated by the interactions with one another. One of the functions they perform is metabolism. This is a process where protein enzymes collectively break down large nutrients such as carbohydrates into smaller molecules, turning them into biofuels or building blocks of other biomass in a cell. This project will study how these enzymes assemble into complexes that regulate or are regulated by metabolism. The knowledge learned from this project will enable far-reaching impacts on the efficient production of biofuels or biomass that benefits the bioeconomy. This project will actively recruit the transfer and continuing students from the community colleges to participate in research at the University of Washington at Seattle (UW) through collaboration with the Pacific Northwest Louise-Stokes Alliance for Minority Participation (PNW LSAMP). The transfer and continuing undergraduate students at UW are derived prominently from the historically under-represented marginalized (URM) groups in Science, Technology, Engineering, and Mathematics (STEM). The broader impact from this program will bolster the retention of transfer and continuing students in STEM higher education and augment the number of URM students going into graduate programs.The goal of this project is to establish testable models of protein assemblies in response to metabolic changes in a cell. Sequential protein enzymes form transient supramolecular assemblies, or metabolons, in a metabolic pathway within living cells. We will elucidate the physical mechanism responsible for their assembly into spatial networks, and how these complexes regulate or are regulated by metabolism with computer simulations. This work will build on an advanced theoretical framework to characterize the rapid formation and disassembly of molecular clusters in a crowded, open multicomponent system, with quantitative variables learned from experimental data and protein structural models. The expected outcome will provide novel opportunities to develop empirically testable hypotheses derived from complex molecular models as biomarkers to predict a cell's metabolic state. The long-term goal of the research program aligns with one of the ten big ideas from the NSF on Understanding the Rule of Life.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.