Effective synchronization of gene expression in cell population based on periodic environmental signals

• Applicant: Professor Dr. Alexander Grünberger
• Subject Area: Biological Process Engineering
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 516641394

Controlling gene expression in cell population finds a lot of applications in diverse fields of research ranging from bioengineering to biomedicine, but is hampered by the biological noise inherent to cellular systems. To this end, being able to entrain cell population i.e., by synchronizing gene expression, is gaining more interest. In our previous work, we have developed an experimental set-up allowing us to set the rate of environmental fluctuations based on the intrinsic switching rate of cellular systems. Accordingly, in this set-up, cell population is exposed to reliable signals only i.e., signals whose amplitude and frequency are directly compatible with the dynamics of the sensing machinery of the microbes and the resulting phenotypic switching rate. Based on this, we found that these reliable environmental perturbations led to a significant decrease in the stochastic component of switching, leading to a more homogeneous and oscillating gene expression profile. However, this reduction was not observed for all the gene circuits investigated, or to a lesser extent for some of them. Also, the frequency of the oscillation in gene expression is not the same for all the systems considered. This project brings together two research teams from Belgium (ULiège) and Germany (UBielefeld) specialized in the analysis of microbial population dynamics at a single cell resolution. Both partners have developed specific expertise and approaches i.e., Segregostat for ULiège and single cell cultivation microfluidics for UBielefeld, that will be combined in an attempt to generalize a cell population entrainment protocol based on the genetic structure of E. coli. Besides the theoretical aspect that is key for a better understanding about the phenotypic plasticity of microbial population in natural ecosystems, our findings could also be exploited through different applications ranging from bioproduction to biomedicine.

• DFG Programme: Research Grants
• International Connection: Belgium
• Cooperation Partner: Professor Dr. Frank Delvigne