Biology subjects

Ghaffarinasab, S.

Publications and source records attributed to Ghaffarinasab, S..

4 recordsLinked to original sources

bioRxiv2025

Cell Growth Simulator: a user-friendly web server for growth balance analysis

GBA Solver is a web-based application that enables efficient construction and numerical solution of coarse-grained growth balance analysis (GBA) models containing up to 20 reactions. The platform features an intuitive spreadsheet-based interface that eliminates the need for programming, integrates kinetic parameters from the BRENDA enzyme database, and provides interactive visualizations for model exploration. By lowering technical barriers, GBA Solver makes GBA modeling accessible to a wider scientific community, expanding the computational toolkit for investigating cell metabolism and growth. GBA Solver is freely available at: https://cellgrowthsim.com/. The source code is available at: https://gitlab.cs.uni-duesseldorf.de/general/ccb/GBASolver.

cell biology↗

bioRxiv2025

Autoinduction expression systems by AHL-mediated quorum-sensing circuits in Synechococcus elongatus PCC 7942

Despite significant potential for cyanobacteria as sustainable bioproduction chases, there are limited examples of scaled cyanobacterial bioproduction. In part, this is because most cyanobacterial species are poorly adapted to bioreactor cultivation conditions and lack features that facilitate biomass growth and harvesting at scale. We explored quorum sensing (QS) pathways derived from heterotrophic microbes as a method for autoinduction of gene expression circuits coordinated to population density in cyanobacteria. Here, we integrated genetic modules designed to produce and detect the diffusible QS signal, acyl-homoserine lactones (AHLs), in the cyanobacterial model, Synechococcus elongatus PCC 7942 (S. elongatus). We demonstrate that S. elongatus heterologously produces sufficient AHL signals to activate gene expression in a dose-dependent and population density-responsive manner. A hybrid combination of AHL synthesis enzyme from Vibrio fischeri (Lux system) with the transcription factor receiver from Pseudomonas aeruginosa (Las system) provides an ideal activation ratio and mitigates toxicity observed with some AHL systems. As a proof of concept, we coupled the QS pathway to the expression of a cell division inhibitory gene, cdv3, facilitating late-phase cell elongation, cell sedimentation, and improved biomass recovery. Our findings provide a foundation for the development of auto-induction systems leverageable to improve cyanobacterial biotechnology applications.

microbiology↗

bioRxiv2023

Metabolic complexity increases adaptability

Bacteria show a striking ability to adapt to new environments through horizontal gene transfer. Anecdotal evidence suggests that some bacteria are more adaptable than others: e.g., intestinal E. coli frequently spin off pathogenic strains adapted to other human tissues, while gastric Helicobacter pylori do not. However, it is unclear what determines the ability of individual strains or species to adapt to new environments. Here, we use pan-genome scale modeling to explore the ability of 102 different unicellular organisms to adapt to each of 5000+ diverse nutritional environments. While the small metabolic systems of specialized endosymbionts typically require 50+ additional metabolic reactions to adapt to new environments, different strains of the generalist E. coli require on average less than 5 new reactions. Thus, there is a positive feedback between metabolic complexity and adaptability, contrary to speculations that complex systems are generally less adaptable.

evolutionary biology↗

bioRxiv2023

Growth balance analysis models of cyanobacteria for understanding resource allocation strategies

Cyanobacteria have emerged as attractive microbial cell factories, as they can convert atmospheric CO2 and sunlight into valuable chemicals. To increase their growth and productivity, one should aim to optimize the allocation of limited cellular resources across different metabolic processes. Here, we developed two growth balance analysis (GBA) models for the cyanobacterium Synechocystis sp. PCC 6803. In its biological assumptions, the models closely related to an existing coarse-grained model, while its mathematical formulation is heavily streamlined. We show that the GBA models provide virtually identical predictions about cellular resource allocation among photosynthesis, carbon metabolism, and the protein translation machinery under different environmental conditions as the previous, mathematically more involved model. Our model also captures the effects of photodamage on proteome allocation and the resulting growth rates. We further show how the GBA model can be easily extended to include more reactions, leading to a second GBA model capable of new predictions about the cellular resource allocation. Balanced growth models of the type presented here can easily expanded to include more biological details, providing a useful toolbox for the understanding of the physiological capabilities of cyanobacteria, their allocation of cellular resources, and the potential of their bioengineering for optimized biomass production.

systems biology↗