ERI: Modeling Bacterial Microcompartment Assembly Using a Data-Driven Multiscale Framework

微生物的工业应用范围正在扩大。燃料、化学品和疫苗的生产只是最近的几个应用。由于中间化合物的毒性，有些产品不能由微生物制造。该项目的重点是解决毒性问题的一种解决方案，将毒性反应限制在细胞内的一个单独的隔室中。该项目的重点是自然发生的细菌微区室。 目标是确定控制其大小，形状和组成的组织原则。研究成果将被改编成动手学习模块，让附近高中的本科生和代表性不足的群体接触生物学、物理学、数据科学、工程学和计算机建模的综合方面。该项目将调查盐囊菌的微区室。该模型系统最近被表征为具有高分辨率结构信息。调节微室壳组装的必需蛋白质相互作用将通过使用系统降维技术推导计算模型进行研究。该研究计划包括两个主要目标：（1）量化蛋白质寡聚化的自由能景观和（2）使用粗粒度组装模拟对控制微区室形态的分子决定因素进行分类。计算框架将利用系统的多尺度算法作为假设检验工具。这将为微观和宏观蛋白质组装行为之间的关系提供一个新的视角。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。

The scope of industrial usage of microbes is increasing. Production of fuels, chemicals, and vaccines are just a few of the most recent applications. Some products cannot be made by microbes because of the toxicity of intermediate compounds. This project is focused on one solution to the toxicity problem, confining the toxic reactions to a separate compartment inside the cell. The focus of this project is on bacterial microcompartments that occur naturally. The goal is to identify the organizing principles that control their size, shape, and composition. Research outcomes will be adapted into hands-on learning modules to expose undergraduates and underrepresented groups at nearby high schools to integrated aspects of biology, physics, data science, engineering, and computer modeling.This project will investigate the Haliangium ochraceum microcompartment. This model system was recently characterized with high- resolution structural information. Essential protein interactions that regulate the assembly of the microcompartment shells will be investigated by deriving computational models using systematic dimensional reduction techniques. The research plan includes two main objectives: (1) To quantify free energy landscapes for protein oligomerization and (2) To classify molecular determinants that control microcompartment morphology using coarse-grained assembly simulations. The computational framework will leverage systematic multiscale algorithms as hypothesis testing tools. This should provide a novel perspective on the relationship between microscopic and macroscopic protein assembly behavior.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.