Research

 1. Phenotypic Diversification and Collective Behavior in Cell Populations

Phenotypic diversification of isogenic cell populations leads to behaviors such as bet-hedging and division of labor. The lab focuses on understanding how cells respond to extracellular stimuli, driving coordinated population dynamics.

Key publications:

• Binder, D., Drepper, T., Jaeger, K.-E., Delvigne, F., Wiechert, W., Kohlheyer, D., Grünberger, A., 2017. Homogenizing bacterial cell factories: Analysis and engineering of phenotypicheterogeneity.

Metabolic Engineering 42, 145–156.

https://doi.org/10.1016/j.ymben.2017.06.009

 

• Delvigne, F., Zune, Q., Lara, A.R., Al-Soud, W., Sorensen, S.J., 2014. Metabolic variabilityin bioprocessing: implications of microbial phenotypic heterogeneity.

Trends inbiotechnology 32, 608–616.

https://doi.org/10.1016/j.tibtech.2014.10.002

2. Cellular Entropy and Fitness-Entropy (F-E) Compensation Mechanism

Cellular entropy is a key concept developed by the lab to quantify diversification within cell populations. The lab’s findings indicate that switching costs, which lead to fitness loss upon phenotype switching, drive population diversification with Fitness-Entropy (F-E) compensation emerging as a key mechanism for coping with these costs.

Key publications:

· Henrion, L., Martinez, J.A., Vandenbroucke, V., Delvenne, M., Telek, S., Zicler, A., Grünberger, A., Delvigne, F., 2023. Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability.

Nat Commun 14, 6128.

https://doi.org/10.1038/s41467-023-41917-z

3. Cell-Machine Interfaces for Bioprocesses

The lab developed the Segregostat, a cell-machine interface based on reactive flow cytometry to control gene expression in microbial populations in real-time. This technology allows for dynamic manipulation of populations in response to environmental changes.

Key publications:

· Delvigne, F., Henrion, L., Vandenbroucke, V., Martinez, J.A., 2023. Avoiding the All-or-None Response in Gene Expression During E. coli Continuous Cultivation Based on the On-Line Monitoring of Cell Phenotypic Switching Dynamics.

Methods Mol Biol 2617, 103–120.

https://doi.org/10.1007/978-1-0716-2930-7_7

 

· Kinet, R., Richelle, A., Colle, M., Demaegd, D., Von Stosch, M., Sanders, M., Sehrt, H., Delvigne, F., Goffin, P., 2024. Giving the cells what they need when they need it: Biosensor-based feeding control.

Biotechnol Bioeng.

https://doi.org/10.1002/bit.28657

 

· Nguyen, T.M., Telek, S., Zicler, A., Martinez, J.A., Zacchetti, B., Kopp, J., Slouka, C., Herwig, C., Grünberger, A., Delvigne, F., 2021. Reducing phenotypic instabilities of a microbial population during continuous cultivation based on cell switching dynamics.

Biotechnol Bioeng.

https://doi.org/10.1002/bit.27860

 

· Sassi, H., Nguyen, T.M., Telek, S., Gosset, G., Grünberger, A., Delvigne, F., 2019. Segregostat: a novel concept to control phenotypic diversification dynamics on the example of Gram-negative bacteria.

Microbial Biotechnology 12, 1064–1075.

https://doi.org/10.1111/1751-7915.13442

4. Stabilization of microbial Co-cultures and Control of Complex Phenotypes

Research in the lab focuses on stabilizing microbial co-cultures and managing complex phenotypes such as general stress responses in various microbes, protein secretion and biofilm switching at a single cell level.

Key publications:

· Hartmann, F.S.F., Grégoire, M., Renzi, F., Delvigne, F., 2024. Single cell technologies for monitoring protein secretion heterogeneity.

Trends Biotechnol S0167-7799(24)00040–4.

https://doi.org/10.1016/j.tibtech.2024.02.011

 

· Kakahi, F.B., Kang, D., Volke, D.C., Wirth, N.T., Nikel, P.I., Delvigne, F., 2021. Extracellular DNA (eDNA) enables early detection of the phenotypic switch of Pseudomonas sp. during biofilm development. bioRxiv 2021.02.11.430776.

https://doi.org/10.1101/2021.02.11.430776

 

· Martinez, J.A., Bouchat, R., Gallet de Saint Aurin, T., Martínez, L.M., Caspeta, L., Telek, S., Zicler, A., Gosset, G., Delvigne, F., 2024. Automated adjustment of metabolic niches enables the control of natural and engineered microbial co-cultures.

bioRxiv 2024.05.14.594082.

https://doi.org/10.1101/2024.05.14.594082

 

· Martinez, J.A., Delvenne, M., Henrion, L., Moreno, F., Telek, S., Dusny, C., Delvigne, F., 2022. Controlling microbial co-culture based on substrate pulsing can lead to stability through differential fitness advantages.

PLoS Comput Biol 18, e1010674.

https://doi.org/10.1371/journal.pcbi.1010674

5. Artificial Cells and Simplified Systems to Study Fundamental Cellular Principles

The lab is investigating the use of artificial cells and simplified systems to study the fundamental principles of cellular behavior. This research aims to decouple complex interactions in natural systems and dissect the Fitness-Entropy compensation mechanism.