Emergent Protein Assemblies in Cytoplasm

蛋白质是细胞内的马匹，参与细胞功能的方方面面。它们通过相互作用促进形成更高顺序的组件来发挥作用。它们执行的功能之一是新陈代谢。这是一个蛋白质酶集体将碳水化合物等大型营养物质分解成较小分子的过程，将它们转化为生物燃料或在细胞中构建其他生物量。这个项目将研究这些酶如何组装成调节新陈代谢或受新陈代谢调节的复合体。从该项目中学到的知识将对生物燃料或生物质的有效生产产生深远影响，从而使生物经济受益。该项目将通过与太平洋西北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校生和继续学生参加华盛顿大学西雅图分校(UW)的研究。威斯康星大学的转学和继续本科学生主要来自科学、技术、工程和数学(STEM)中历史上代表性不足的边缘化群体(URM)。这一计划的更广泛影响将支持STEM高等教育中留住转学和继续教育的学生，并增加进入研究生课程的URM学生的数量。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。连续的蛋白质酶在活细胞内的代谢途径中形成瞬时的超分子组装或代谢物。我们将通过计算机模拟来阐明它们组装成空间网络的物理机制，以及这些复合体是如何调节或被代谢调节的。这项工作将建立在一个先进的理论框架上，以描述拥挤、开放的多组分系统中分子簇的快速形成和拆分，并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，开发从复杂分子模型衍生的经验性可验证假说，作为预测细胞代谢状态的生物标记物。该研究计划的长期目标与NSF关于理解生活规则的十大想法之一一致。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.