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

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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.