Biomedical research institute
     
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    Robustness and evolvability of life

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    Team leader:

     

    Some of the most challenging medical problems, like emerging infectious diseases and antimicrobial drug resistance, are fundamentally evolutionary phenomena. In order to prevent their emergence, it is necessary to understand them. However, we do not understand all of the underlying molecular mechanisms neither how the environmental heterogeneity and fluctuations drive these important evolutionary processes. Our team aims to fill some of the gaps currently existing in the comprehension of these complex phenomena.

     

     

    Objectives

    Our team study how phenotypic and genetic variation is generated in bacterial populations, especially in response to environmental stresses, and how they modulate evolvability and robustness of these populations. We are also elucidating molecular mechanisms driving evolution of persistence and resistance to antibiotic. Besides generating fundamental knowledge, our research may facilitate development of new therapeutic strategies to predict and combat the emergence of antibiotic resistances.

    In order to face conceptual and technical challenges posed by these projects, besides genetic, genomic and molecular biology methods, we are developping novel methodologies allowing studying single live bacterial cells. For this, we developed an experimental framework based on the microfluidic technology. We are also developing novel assays allowing monitoring mutation and mistranslation error rates, as well as metabolic state of living single cells.

     

    Main publications

    • Matic, I (2019) Mutation rates heterogeneity increases odds of survival in unpredictable environments. Mol Cell 75:421-425
    • Woo, A.C., Faure, L., Dapa, T., and Matic, I. (2018) Heterogeneity of the spontaneous DNA replication errors in single isogenic Escherichia coli cells. Science Advances. 4: eaat1608
    • Matic, I. (2018) The major contribution of the DNA damage-triggered reactive oxygen species production to cell death: implications for antimicrobial and cancer therapy. Current Genetics, 64(3), 567-569
    • Giroux, X., Su, W-L., Bredeche, M-F., and Matic, I. (2017). Maladaptive DNA repair activity is the ultimate contributor to the death of trimethoprim-treated cells under aerobic and anaerobic conditions. PNAS USA, 114:11512-11517
    • Mathieu, A., Fleurier, S., Frénoy, A., Dairou, J., Bredeche, M.F., Sanchez-Vizuete, P., Song, X.,and Matic, I. (2016) Discovery and Function of a General Core Hormetic Stress Response in E. coli Induced by Sublethal Concentrations of Antibiotics. Cell Reports 7: 46-57