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Fuentes-Cabrera, M.

Publications and source records attributed to Fuentes-Cabrera, M..

3 recordsLinked to original sources

Predicting partner fitness based on spatial structuring in a light-driven microbial community

Microbial communities have vital roles in systems essential to human health and agriculture, such as gut and soil microbiomes, and there is growing interest in engineering designer consortia for applications in biotechnology (e.g., personalized probiotics, bioproduction of high-value products, biosensing). The capacity to monitor and model metabolite exchange in dynamic microbial consortia can provide foundational information important to understand the community level behaviors that emerge, a requirement for building novel consortia. Where experimental approaches for monitoring metabolic exchange are technologically challenging, computational tools can enable greater access to the fate of both chemicals and microbes within a consortium. In this study, we developed an in-silico model of a synthetic microbial consortia of sucrose-secreting Synechococcus elongatus PCC 7942 and Escherichia coli W. Our model was built on the NUFEB framework for Individual-based Modeling (IbM) and optimized for biological accuracy using experimental data. We showed that the relative level of sucrose secretion regulates not only the steady-state support for heterotrophic biomass, but also the temporal dynamics of consortia growth. In order to determine the importance of spatial organization within the consortium, we fit a regression model to spatial data and used it to accurately predict colony fitness. We found that some of the critical parameters for fitness prediction were inter-colony distance, initial biomass, induction level, and distance from the center of the simulation volume. We anticipate that the synergy between experimental and computational approaches will improve our ability to design consortia with novel function. Author SummaryMicrobial communities, play important, yet poorly understood roles in health and agriculture. As we develop a better understanding of how these communities interact together, as well as with their host organisms, there is growing interest in engineering communities with specific functions, such as for treating disease, personalized probiotics, or aiding plants with nutrient uptake. To better understand how these microbes interact with each other, we want to monitor the exchange of metabolites and the locations of the microbes, tasks which at present are technically challenging, if not impossible. Where experimental approaches for monitoring metabolites are limited, computational tools can enable greater access to the fate of both chemicals and microbes within a community. In this study, we developed a computerized model of a synthetic microbial community of two bacteria, one which performs photosynthesis and supplies sugar and another which consumes the sugar for growth. We showed that the relative level of sugar secretion regulates not only the steady-state support for the consumer partners growth, but also how the community changes with time. To determine the importance of spatial organization within the community, we fit a model and used it to predict colony growth. We anticipate that the synergy between experimental and computational approaches will improve our ability to design microbial communities with new functions.

bioengineering↗

Investigating Carboxysome Morphology Dynamics with a Rotationally Invariant Variational Autoencoder

Carboxysomes are a class of bacterial microcompartments that form proteinaceous organelles within the cytoplasm of cyanobacteria and play a central role in photosynthetic metabolism by defining a cellular microenvironment permissive to CO2 fixation. Critical aspects of the assembly of the carboxysomes remain relatively unknown, especially with regard to the dynamics of this microcompartment. We have recently expressed an exogenous protease as a way of gaining control over endogenous protein levels, including carboxysomal components, in the model cyanobacterium Synechococcous elongatus PCC 7942. By utilizing this system, proteins that compose the carboxysome can be tuned in real-time as a method to examine carboxysome dynamics. Yet, analysis of subtle changes in carboxysome morphology with microscopy remains a low-throughput and subjective process. Here we use deep learning techniques, specifically a Rotationally Invariant Variational Autoencoder (rVAE), to analyze the fluorescence microscopy images and quantitatively evaluate how carboxysome shell remodelling impacts trends in the morphology of the microcompartment over time. We find that rVAEs are able to assist in the quantitative evaluation of changes in carboxysome location, shape, and size over time. We propose that rVAEs may be a useful tool to accelerate the analysis of carboxysome assembly and dynamics in response to genetic or environmental perturbation, and may be more generally useful to probe regulatory processes involving a broader array of bacterial microcompartments.

microbiology↗

Investigating the growth of an engineered strain of Cyanobacteria with an Agent-Based Model and a Recurrent Neural Network

A computational framework combining Agent-Based Models (ABMs) and Deep Learning techniques was developed to help design microbial communities that convert light and CO2 into useful bioproducts. An ABM that accounts for CO2, light, sucrose export rate and cell-to-cell mechanical interactions was used to investigate the growth of an engineered sucrose-exporting strain of Synechococcus elongatus PCC 7942. The ABM simulations produced population curves and synthetic images of colony growth. The curves and the images were analyzed, and growth was correlated to nutrients availability and colonies initial spatial distribution. To speed up the ABM simulations, a metamodel based on a Recurrent Neural Network, RNN, was trained on the synthetic images of growth. This metamodel successfully reproduced the population curves and the images of growth at a lower computational cost. The computational framework presented here paves the road towards designing microbial communities containing sucrose-exporting Synechococcus elongatus PCC 7942 by exploring the solution space in silico first.

microbiology↗