Collaborative Research: Interrogating the interconnection of structural and metabolic dynamics of evolutionarily distinct bacterial microcompartment

About This Grant

Biology is organized in space and time to allow organisms to grow and compete. Even the simplest bacteria use miniature, soccer ball-like “microcompartments” to house pathways of chemical reactions, allowing them to grow and process molecules that would otherwise be unavailable to them. Over 45 different types (“phyla”) of bacteria have genes for such microcompartments, including some that grow using sunlight and some which grow in our gut. This project studies the impact of geometry and permeability of microcompartments in two distantly related bacteria under varying realistic environments. Studying two distinct organisms will provide generalizable understanding of how such microcompartments are built and regulated. This knowledge will be useful to provide new paths for bioengineering chemical production of specialty chemicals as well as for control of bacterial pathogens. The team will couple these research efforts with educational and training outreach programs. The PIs will integrate undergraduate researchers into the research and develop a new case study for undergraduate courses used by at least 4 universities on protein engineering. In concert with the scientific research, the team will conduct an analysis of the potential of synthetic biology to support new manufacturing strategies as part of the growing bioeconomy. This study compares two representative and evolutionarily distinct types of bacterial microcompartments (BMCs): anabolic carboxysomes and the 1,2 propanediol catabolic metabolosome. The underlying hypothesis of this proposal is that BMC geometry and permeability are dynamically regulated features that can be tuned to promote efficient metabolism under changing contexts in response to species specific cellular needs. To test this hypothesis, the PIs will evaluate the impact of BMC structural modulation on metabolic function, using an interdisciplinary combination of bacterial genetics, synthetic biology, and predictive and data-informed modeling. Aim 1 couples predictive dynamical systems modeling with genetic and environmental methods to modulate physical features of BMCs and determine the impact on metabolic function. Aim 2 extends the integrated modeling and experimental approach to assess the importance of BMC shell integrity (i.e., having a closed shell) on controlling the local metabolic environment. Aim 3 quantitatively evaluates the dynamic exchange of BMC shell proteins in vivo under varying environmental conditions and integrates these data into a population-level model of microcompartments within cells to inform how BMC shell remodeling may dynamically impact metabolism. The policy analysis integrated into this program includes a landscape review of the state of bioengineering in BMC-containing bacteria, the breadth of potential bioproducts which could be manufactured in BMCs, and the current companies and research groups involved in development. Educational materials will be disseminated nationally and internationally through the Engineering Biology Research Consortium. Graduate students and undergrads who will be trained as a part of this proposal will cross-trained in mathematics and biology, directly engaged in science and society discussions, to provide interdisciplinary training and a broader perspective on the role of science with society. Cross-training will be expanded to a broader range of trainees at the graduate, postdoc and faculty level through career panels and mentor training workshops. This project is supported by the Cellular Dynamics and Function program in Molecular and Cellular Biosciences. 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.