Biology subjects

Delvenne, M.

Publications and source records attributed to Delvenne, M..

5 recordsLinked to original sources

bioRxiv2025

Overriding bioprocess perturbations with a cell machine interface for reliable microbial stress-response control

Controlling cell population dynamics and phenotypic diversification is a key objective in systems and synthetic biology, particularly for ensuring uniform responses from engineered gene circuits. While cell-machine interfaces have been employed to modulate host-gene circuit interactions, environmental perturbations typical of industrial bioreactor conditions remain underexplored. In this study, we investigate the impact of such perturbations on the general stress response in Escherichia coli and Saccharomyces cerevisiae. Using scale-down bioreactor experiments, we evaluate the performance of the Segregostat, a real-time control system that leverages automated flow cytometry to induce dynamic nutrient shifts. The Segregostat achieves robust stress response control, even under severe perturbations such as extended residence times in a two-compartment reactor. We hypothesize that this robustness arises from the systems ability to amplify host-compatible fluctuations beyond bioreactor-induced perturbations. Our findings highlight the importance of integrating environmental factors into control strategies for reliable gene circuit behavior in industrial bioprocessing environments.

bioengineering↗

bioRxiv2025

A Fitness Entropy Compensation effect set the trade-off between growth and gene expression in cell populations

We present findings on a Fitness-Entropy Compensation (FEC) mechanism which offsets the activation of gene circuits that compromise survival. It counteracts the resulting fitness reduction by increasing the diversity in gene expression among individual cells within the population. This diversity, quantified by the Shannon entropy, enables cells with lower expression levels to support the survival of the entire population. We investigated the presence of FEC in a range of synthetic and stress-related genetic circuits in continuous culture. Our results reveal that it effectively stabilizes cell populations by mitigating the detrimental trade-offs between growth and gene expression. This stabilization is due to the reduced growth rate of the induced phenotype that leads to environmental changes, decreases induction strength, and promotes escape from unfit states. These findings suggest that the FEC mechanism may be a universal strategy for stabilization in various cellular systems and set the basis for a quantitative description of the trade-off between growth and gene expression and its consequences at the population level.

systems biology↗

bioRxiv2023

Long-term phenotypic and genomic instability of an industrial ethanol-producing and C5-utilizing Saccharomyces cerevisiae strain

The performance of a microbial fermentation for the production of a bio-based product requires long-term robustness and stability of the producer strain. Here, we explored the genetic and metabolic stability of an industrial ethanol-producer Saccharomyces cerevisiae strain that was engineered by chromosomal integration of several copies of transgenes allowing co-fermentation of D-xylose and L-arabinose with glucose. Through sequential batch cultures in controlled bioreactor, it was found that this strain exhibited significant fluctuation of xylose and arabinose consumption starting at 50th generation and onward. Also, clones that have partly or completely lost the ability to assimilate arabinose or xylose were isolated, and this alteration was due to reduced copy number of the transgenes encoding the enzymes of the C5 sugar assimilation. However, subpopulation enriched with low or high RAD52 expression, whose expression level was reported to be proportional to homologous recombination rate did not exhibit defect in C5-sugar assimilation, arguing that other mechanisms may be responsible for copy number variation of transgenes. Overall, this work underscored genetic and metabolic instabilities, which although modest under our conditions, could in the longer term and under more stringent industrial conditions lead to a reduction of production performance.

bioengineering↗

bioRxiv2023

Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability

Isogenic cell populations can cope with stress conditions by switching to alternative phenotypes. Even if it can lead to increased fitness in a natural context, this feature is typically unwanted for a range of applications (e.g., bioproduction, synthetic biology, biomedicine...) where it tends to decrease the controllability of the cellular response. However, little is known about the diversification profiles that can be adopted by a cell population. We characterized the diversification dynamics for various systems (bacteria and yeast) and for different phenotypes (utilization of alternative carbon sources, general stress response and more complex development patterns). Interestingly, our results suggest that the diversification dynamics and the fitness cost associated with cell switching are coupled. For quantifying the contribution of the switching cost on population dynamics, we built a stochastic model that allowed us to reproduce the dynamics observed experimentally and identified three diversification regimes, i.e., constrained (at low switching cost), dispersed (at medium and high switching cost), and bursty (for very high switching cost). Furthermore, we used a cell-machine interface that we call the Segregostat to demonstrate that different levels of control can be applied to these diversification regimes, enabling applications involving more precise cellular responses.

microbiology↗

bioRxiv2022

Controlling microbial co-culture based on substrate pulsing can lead to stability through differential fitness advantages

Microbial consortia are an exciting alternative for increasing the performances of bioprocesses for the production of complex metabolic products. However, the functional properties of microbial communities remain challenging to control, considering the complex interaction mechanisms occurring between co-cultured microbial species. Indeed, microbial communities are highly dynamic and can adapt to changing environmental conditions through complex mechanisms, such as phenotypic diversification. We focused on stabilizing a co-culture of Saccharomyces cerevisiae and Escherichia coli in continuous cultures. Our preliminary data pointed out that transient diauxic shifts could lead to stable co-culture by providing periodic fitness advantages to the yeast. Based on a computational toolbox called MONCKS (for MONod-type Co-culture Kinetic Simulation), we were able to predict the dynamics of diauxic shift for both species based on a cybernetic approach. This toolbox was further used to predict the frequency of diauxic shift to be applied to reach co-culture stability. These simulations were successfully reproduced experimentally in continuous bioreactors with glucose pulsing. Finally, based on a bet-hedging reporter, we observed that the yeast population exhibited an increased phenotypic diversification process in co-culture compared with mono-culture, suggesting that this mechanism could be the basis of the metabolic fitness of the yeast.

systems biology↗